Recently Published

[1] A first-in-class β-glucuronidase responsive conjugate for selective dual targeted and photodynamic therapy of bladder cancer

V. F. Otvagin, L. V. Krylova, N. N. Peskova, N. S. Kuzmina, E. A. Fedotova, A. V. Nyuchev, Y. V. Romanenko, O. I. Koifman, S. Z. Vatsadze, H. G. Schmalz, I. V. Balalaeva, A. Y. Fedorov, Eur. J. Med. Chem. 2024, 269, 17. DOI: https://www.doi.org/10.1016/j.ejmech.2024.116283

Abstract

In this report, we present a novel prodrug strategy that can significantly improve the efficiency and selectivity of combined therapy for bladder cancer. Our approach involved the synthesis of a conjugate based on a chlorin- e 6 photosensitizer and a derivative of the tyrosine kinase inhibitor cabozantinib, linked by a beta -glucuronidase- responsive linker. Upon activation by beta -glucuronidase, which is overproduced in various tumors and localized in lysosomes, this conjugate released both therapeutic modules within targeted cells. This activation was accompanied by the recovery of its fluorescence and the generation of reactive oxygen species. Investigation of photodynamic and dark toxicity in vitro revealed that the novel conjugate had an excellent safety profile and was able to inhibit tumor cells proliferation at submicromolar concentrations. Additionally, combined therapy effects were also observed in 3D models of tumor growth, demonstrating synergistic suppression through the activation of both photodynamic and targeted therapy.

[2] A pH-Sensitive Double Chromophore Fluorescent Dye for Live-Tracking of Lipophagy

P. M. Engelhardt, M. Veronese, A. A. Eryigit, A. Das, A. T. Kaczmarek, E. I. Rugarli, H. G. Schmalz, Chem.-Eur. J. 2024, 10. DOI: https://www.doi.org/10.1002/chem.202400808

Abstract

Lipid droplet (LD) degradation provides metabolic energy and important building blocks for various cellular processes. The two major LD degradation pathways include autophagy (lipophagy), which involves delivery of LDs to autolysosomes, and lipolysis, which is mediated by lipases. While abnormalities in LD degradation are associated with various pathological disorders, our understanding of lipophagy is still rudimentary. In this study, we describe the development of a lipophilic dye containing two fluorophores, one of which is pH-sensitive and the other pH-stable. We further demonstrate that this "Lipo-Fluddy" can be used to visualize and quantify lipophagy in living cells, in an easily applicable and protein label-free approach. After estimating the ability of compound candidates to penetrate LDs, we synthesized several BODIPY and (pH-switchable) rhodol dyes, whose fluorescence properties (incl. their photophysical compatibility) were analyzed. Of three Lipo-Fluddy dyes synthesized, one exhibited the desired properties and allowed observation of lipophagy by fluorescence microscopy. Also, this dye proved to be non-toxic and suitable for the examination of various cell lines. Moreover, a method was developed to quantify the lipophagy process using flow cytometry, which could be applied in the future in the identification of lipophagy-related genes or in the screening of potential drugs against lipophagy-related diseases. Live monitoring the fate of lipid droplets (LD) within cells! To visualize and quantify lipophagy in an easily applicable, non-toxic and protein label-free approach by means of fluorescence microscopy, a unique dye called Lipo-Fluddy-1 was developed. This synthetic dye is characterized by a high lipophilicity and contains two chromophores, one of which only fluoresces at low pH. Its usefulness was demonstrated by the flow cytometry investigation of lipophagy in several cell lines.+ image

[3] Supramolecular Behaviour of N,N′-Bridged Guanidinium Nitrates in the Crystalline State: Identification of Privileged Hydrogen Bond Networks

R. G. Wüstenberg, J. M. Neudörfl, H. G. Schmalz, Isr. J. Chem. 2023, 63, 15. DOI: https://www.doi.org/10.1002/ijch.202300018

Abstract

Using the marine natural product ptilocaulin as a starting point, the supramolecular behavior of N,N '-bridged guanidinium nitrates in the crystalline state was investigated. For this purpose, various N,N '-bridged guanidines were synthesized (typically by condensation of a 1,2- or 1,3-diamine with cyanogen bromide) and subsequently converted into their nitrate salts with nitric acid. The crystal structures of 28 samples were determined by single crystal X-ray crystallography and revealed the existence of a few privileged, recurring supramolecular motifs (hydrogen bond networks) formed by charge-assisted self-assembly. A topological analysis of possible pseudo-2D-patterns derived from the 1 : 1 ion pairs (generated by salt bridge formation between a N,N '-bridged guanidinium cation and a nitrate anion) through additional H-bonding uncovered only five conceivable regular structural motifs: (1) a linear chain, (2) an alternating (zig-zag) chain, (3) a double chain, (4) a tape/ribbon-type structure, and (5) a cyclotrimer. Experimentally, only the first four of these motives were observed while the cyclotrimer, as a non-infinite and therefore particular super-structure, did not occur. Other H-bonding patterns were found (in three cases) when water was incorporated in the crystals. In two cases, polymorphism was observed. The identified supramolecular preferences prove the value of N,N '-bridged guanidines as useful and easily tunable building blocks for supramolecular chemistry and crystal engineering.

[4] Enantioselective Nickel-Catalyzed Hydrocyanation of Homostilbenes

J. P. Strache, L. Münzer, A. Adler, D. Blunk, H. G. Schmalz, Eur. J. Org. Chem. 2023, 26, 7. DOI: https://www.doi.org/10.1002/ejoc.202300050

Abstract

We investigated the previously unknown enantioselective Ni-catalyzed hydrocyanation of 1,3-diarylpropenes (homostilbenes). For this purpose, a series of (E)-homostilbenes were prepared by (microwave-assisted) Pd-catalyzed coupling of allylic alcohols with aryl-boronic acids. Employing our established catalyst system formed from Ni(cod)(2) and a TADDOL-derived chiral phosphine-phosphite ligand and using TMSCN as an in situ source of HCN, the hydrocyanation of various homostilbenes was studied. The synthetic usefulness of the methodology was demonstrated in a short synthesis of the new (allo-) colchicine analogue 7-cyano-11-methoxy-colchinol involving an PIDA-mediated oxidative cyclization of the corresponding hydrocyanation product to set up the 7-membered ring. The absolute configuration of 2,4-diphenylbutyronitrile was assigned by comparison of experimental and calculated ECD spectra.

[5] Lessons from the Total Synthesis of Highly Substituted Benzophenone Natural Products

L. Münzer, H. G. Schmalz, Synlett 2023, 34, 1752-1764. DOI: https://www.doi.org/10.1055/a-2039-6440

Abstract

In this account, we summarize the results and experience gained during 20 years of research in the field of polyketidic natural products displaying a tetra-ortho-substituted benzophenone substructure. As demonstrated by the various approaches towards mumbaistatin and pestalone as targets of high biological relevance, the synthesis of such systems is surprisingly difficult due to the intense interactions of the functional groups adjacent to the ketone bridge. We report successes and failures, as well as the discovery of surprising reactivities that are important for understanding the non-enzymatic formation of related compounds in Nature.1 Introduction2 Mumbaistatin3 Pestalone4 Conclusion

[6] Studies Towards the Total Synthesis of Populusone: Stereoselective Construction of Functionalized 2-Oxa-bicyclo 2.2.2 octenes

L. Hemmersbach, H. G. Schmalz, Synlett 2023, 34, 238-242. DOI: https://www.doi.org/10.1055/a-1983-1694

Abstract

A short and efficient synthetic access to functionalized compounds displaying major structural elements of the natural product populusone is elaborated by exploiting a diastereoselective Mukaiyama aldol addition followed by a triflic anhydride-induced oxa-Michael addition to construct the sensitive 2-oxa-bicyclo[2.2.2]octene unit as an enol triflate, which is directly used in a subsequent Suzuki cross -coupling. While attempts to close the strained 10-membered ring by means of Ru-catalyzed ring-closing metathesis were not successful, the developed synthetic scheme opens a rapid synthetic access to advanced intermediates, which may allow the completion of the total synthesis of populusone in the future.

[7] Synthesis of Bifunctional Lipoxin-Derived Enzyme-Triggered CO-Releasing Molecules (LipET-CORMs)

L. Hemmersbach, R. Adam, C. Plevnali, X. M. Zhang, B. Yard, H. G. Schmalz, Eur. J. Org. Chem. 2023, 26, 6. DOI: https://www.doi.org/10.1002/ejoc.202201424

Abstract

In an attempt to develop new anti-inflammatory agents which act by co-release of carbon monoxide (CO) and a specialized pro-resolving mediator, we designed conjugates of a lipoxin A(4) analogue and an acyloxycyclohexadiene-Fe(CO)(3) complex as an esterase-triggered CO-releasing molecule (ET-CORM). After adjustment of the protecting group strategy, two of such compounds were successfully prepared by total synthesis (12 steps; 4-5 % overall yield) starting from deoxy-d-ribose and exploiting a Wittig olefination and an intermolecular Heck reaction as key C-C bond-forming steps. A crucial late reduction of an aryl-ketone moiety in the presence of a highly sensitive dienol ester functionality was achieved with BH3-SMe2 in the presence of catalytic amounts of NaBH4. Both target compounds were dose-dependently toxic towards cultured human umbilical vein endothelial cells (HUVEC), with LipET-CORM 1-A being slightly more toxic. While induction of heme oxygenase 1 (HO-1) in HUVEC was observed for both compounds, they did not inhibit TNF-alpha-mediated VCAM-1 expression in these cells. In M2 polarized macrophages HO-1 expression was more pronounced as compared to M1 polarized macrophages. In both types of macrophages HO-1 expression was downregulated by lipopolysaccharide, but only in M2 macrophages HO-1 expression was rescued by LipET-CORM. 15-Lipoxygenase (15-LO) was only expressed in M2 macrophages and was not influenced by LipET-CORM. Collectively our data demonstrate that LipET-CORMs induce HO-1 expression in endothelial cells and M2 polarized macrophages. The role of the intra-cellular released lipoxin A(4) in resolution of inflammation, however, remains to be assessed.

[8] Isotope-labeled ergothioneine clarifies the mechanism of reaction with singlet oxygen

L. Hartmann, F. P. Seebeck, H. G. Schmalz, D. Gründemann, Free Radic. Biol. Med. 2023, 198, 12-26. DOI: https://www.doi.org/10.1016/j.freeradbiomed.2023.01.023

Abstract

Recently we have uncovered a non-enzymatic multi-step cycle for the regeneration of ergothioneine (ET), after reaction with noxious singlet oxygen (1O2), by glutathione (GSH). When living cells were loaded with ET labeled with deuterium and N-15 atoms (D5-ET) and exposed to light in the presence of a photosensitizer, no loss of deuterium at position 5 of the imidazole ring was observed, in contradiction to our previous mechanistic pro-posal. Therefore, it was necessary to reexamine the in vitro products of ET and 1O2 by liquid chromatography coupled to high resolution mass spectrometry. Pure 1O2 was generated by thermolysis at 37 degrees C of the endo-peroxide DHPNO2. The use of D5-ET enabled us to revise and extend the reaction scheme. On the main pathway, 1O2 attacks the imidazole ring, and the hydroperoxide intermediates are reduced rapidly by ET or GSH via different mechanisms. The intramolecular water elimination from the 5-hydroperoxide described previously is slower and not a part of the cycle. On another side path, 1O2 attacks the sulfur of ET to form a sulfine (S-oxide). The reduction of the sulfine also allows for the complete regeneration of ET. Experiments with methanol instead of water as solvent revealed that, in the absence of GSH, ET was attacked 6 times more frequently at the ring than at the sulfur. In the presence of 1 mM GSH or higher, both side paths were abandoned. ET efficiently captures 1O2 with its ring and can then be regenerated to a large extent by GSH, without enzyme involvement.

[9] Design of an aryne-platform for the synthesis of non-racemic heterocyclic allocolchicinoids

I. A. Gracheva, H. G. Schmalz, E. V. Svirshchevskaya, E. S. Shchegravina, A. Y. Fedorov, Org. Biomol. Chem. 2023, 21, 6141-6150. DOI: https://www.doi.org/10.1039/d3ob00827d

Abstract

A four-step semisynthetic approach towards a highly versatile allocolchicine-related chiral aryne intermediate starting from naturally occurring colchicine was developed, and some of its synthetic transformations were studied. The in situ generated benzyne intermediate afforded a number of non-racemic heterocyclic allocolchicinoids, which were shown to exhibit potent cytotoxicity towards COLO 357, OSA and Raji cells. The proposed methodology is attractive for the synthesis of libraries of new cytotoxic tubulin inhibitors.

[10] Divergent total synthesis of the revised structures of marine anti-cancer meroterpenoids (+)-dysiherbols A-E

C. K. Chong, L. Chang, I. Grimm, Q. L. Zhang, Y. Kuang, B. J. Wang, J. Y. Kang, W. H. Liu, J. Baars, Y. Q. Guo, H. G. Schmalz, Z. Y. Lu, Chem. Sci. 2023, 14, 3302-3310. DOI: https://www.doi.org/10.1039/d3sc00173c

Abstract

We report here a concise and divergent enantioselective total synthesis of the revised structures of marine anti-cancer sesquiterpene hydroquinone meroterpenoids (+)-dysiherbols A-E (6-10) using dimethyl predysiherbol 14 as a key common intermediate. Two different improved syntheses of dimethyl predysiherbol 14 were elaborated, one starting from Wieland-Miescher ketone derivative 21, which is regio- and diastereoselectively alpha-benzylated prior to establishing the 6/6/5/6-fused tetracyclic core structure through intramolecular Heck reaction. The second approach exploits an enantioselective 1,4-addition and a Au-catalyzed double cyclization to build-up the core ring system. (+)-Dysiherbol A (6) was prepared from dimethyl predysiherbol 14via direct cyclization, while (+)-dysiherbol E (10) was synthesized through allylic oxidation and subsequent cyclization of 14. Epoxidation of 14 afforded allylic alcohol 45 or unexpectedly rearranged homoallylic alcohol 44. By inverting the configuration of the hydroxy groups, exploiting a reversible 1,2-methyl shift and selectively trapping one of the intermediate carbenium ions through oxy-cyclization, we succeeded to complete the total synthesis of (+)-dysiherbols B-D (7-9). The total synthesis of (+)-dysiherbols A-E (6-10) was accomplished in a divergent manner starting from dimethyl predysiherbol 14, which led to the revision of their originally proposed structures.

[11] Efficient Solution Phase Synthesis of PPII Helix Mimicking Ena/VASP EVH1 Inhibitors from Proline-Derived Modules (ProMs)

D. Albat, S. Chiha, S. Dohmen, P. M. Engelhardt, H. Sebode, A. Soicke, M. Barone, M. Mueller, R. Kuehne, H. G. Schmalz, Eur. J. Org. Chem. 2023, 26, 5. DOI: https://www.doi.org/10.1002/ejoc.202300771

Abstract

In the search for efficient inhibitors for the enabled/vasodilator-stimulated phosphoprotein homology 1 (EVH1) domain to reduce cell motility in metastatic cancer, we previously developed a toolkit of proline-derived modules (ProMs), which mimic the PPII helix found in the natural -FPPPP- binding motif of EVH1. In this work, we describe the modular assembly of these ProM-based pentapeptidic EVH1 ligands through liquid phase peptide synthesis. We initially used pentafluorophenyl (Pfp) active esters for amide bond formation and built up the growing peptide chain from the C- to the N-terminus. Switching to HATU/DIPEA coupling conditions and changing the directionality of the synthesis from the N- to the C-terminus afforded the target ligands with improved overall yields and purity. Employing a Fmoc-protected (instead of the N-acetylated) phenylalanine derivative as N-terminal building block significantly reduced epimerization. In contrast to the originally used solid phase peptide synthesis (SPPS), the developed solution phase method allowed for a facile alteration of the C-terminal ProM unit and the production of various pentapeptidic ligands in an efficient fashion even on a multigram scale.image

[12] B-nor-methylene Colchicinoid PT-100 Selectively Induces Apoptosis in Multidrug-Resistant Human Cancer Cells via an Intrinsic Pathway in a Caspase-Independent Manner

A. Stein, P. H. N. Thomopoulou, C. Frias, S. M. Hopff, P. Varela, N. Wilke, A. Mariappan, J. M. Neudörfl, A. Y. Fedorov, J. Gopalakrishnan, B. Gigant, A. Prokop, H. G. Schmalz, ACS Omega 2022, 7, 2591-2603. DOI: https://www.doi.org/10.1021/acsomega.1c04659

Abstract

Colchicine, the main active alkaloid from Colchicum autumnale L., is a potent tubulin binder and represents an interesting lead structure for the development of potential anticancer chemotherapeutics. We report on the synthesis and investigation of potentially reactive colchicinoids and their surprising biological activities. In particular, the previously undescribed colchicinoid PT-100, a B-ring contracted 6-exo-methylene colchicinoid, exhibits extraordinarily high antiproliferative and apoptosis-inducing effects on various types of cancer cell lines like acute lymphoblastic leukemia (Nalm6), acute myeloid leukemia (HL-60), Burkitt-like lymphoma (BJAB), human melanoma (MelHO), and human breast adenocarcinoma (MCF7) cells at low nanomolar concentrations. Apoptosis induction proved to be especially high in multidrug-resistant Nalm6-derived cancer cell lines, while healthy human leukocytes and hepatocytes were not affected by the concentration range studied. Furthermore, caspase-independent initiation of apoptosis via an intrinsic pathway was observed. PT-100 also shows strong synergistic effects in combination with vincristine on BJAB and Nalm6 cells. Cocrystallization of PT-100 with tubulin dimers revealed its (noncovalent) binding to the colchicine-binding site of beta-tubulin at the interface to the a-subunit. A pronounced effect of PT-100 on the cytoskeleton morphology was shown by fluorescence microscopy. While the reactivity of PT-100 as a weak Michael acceptor toward thiols was chemically proven, it remains unclear whether this contributes to the remarkable biological properties of this unusual colchicinoid.

[13] Total Synthesis and Antibiotic Properties of Amino-Functionalized Aromatic Terpenoids Related to Erogorgiaene and the Pseudopterosins

C. E. Schumacher, M. Rausch, T. Greven, J. M. Neudorfl, T. Schneider, H. G. Schmalz, Eur. J. Org. Chem. 2022, 2022, 8. DOI: https://www.doi.org/10.1002/ejoc.202200058

Abstract

Following a concept recently introduced by Hergenrother,([6]) the present study addresses the question of whether certain antimicrobially active aromatic (marine) natural products can be converted into more potent broad-spectrum antibiotics by introducing an aminoalkyl side chain. To this end, phenolic mono- and sesquiterpenoids (incl. carvacrol, xanthorrhizol, and 7-hydroxycalamene) as well as the diterpenes 7-hydroxyerogorgiaene and 9-deoxypseudopterosin A were converted into amino-functionalized analogs that display either an amino-methyl or a 2-amino-ethoxy substituent in place of (or next to) the OH group. This was achieved either by Pd-catalyzed nitromethylation/reduction of the aryltriflates, by O-alkylation of the phenols with bromoacetonitrile and subsequent reduction, or by ortho-hydroxymethylation/amination. During the study, an efficient enantioselective total synthesis of 7-hydroxyerogorgiaene (8 steps, 29 % overall yield) and 9-deoxypseudopterosin A (9 steps, 30 % overall yield) was elaborated using an asymmetric cobalt-catalyzed hydrovinylation (91 % ee) of 3-methoxy-4-methyl-styrene as the chirogenic step. Other important C-C bond forming steps include a Pd-catalyzed Suzuki cross-coupling and diastereoselective Lewis acid-mediated cyclization reactions. A total of 16 amino derivatives of natural products were prepared and subsequently tested for their antibacterial properties. Some of the diterpene-derived amines showed high efficacy, not only against Gram-positive (S. aureus SG511, S. aureus HG003, B. subtilis 168; MIC=0.5 to 2 mu g/ml), but also against Gram-negative bacterial strains (E. coli K12; E. coli I-11276b; MIC=8 to 32 mu g/ml). This clearly supported the underlying working hypothesis.

[14] CO-releasing molecules relax rat small mesenteric arteries: contribution of Kv7 channels

R. Schubert, D. Zhang, B. Krause, H. G. Schmalz, P. Wohlfart, B. Yard, Acta Physiol. 2022, 236, 855-855. Abstract

[15] Phenanthroindolizidine Alkaloids Isolated from Tylophora ovata as Potent Inhibitors of Inflammation, Spheroid Growth, and Invasion of Triple-Negative Breast Cancer

I. Reimche, H. Q. Yu, N. P. Ariantari, Z. Liu, K. Merkens, S. Rotfuss, K. Peter, U. Jungwirth, N. Bauer, F. Kiefer, J. M. Neudörfl, H. G. Schmalz, P. Proksch, N. Teusch, Int. J. Mol. Sci. 2022, 23, 32. DOI: https://www.doi.org/10.3390/ijms231810319

Abstract

Triple-negative breast cancer (TNBC), representing the most aggressive form of breast cancer with currently no targeted therapy available, is characterized by an inflammatory and hypoxic tumor microenvironment. To date, a broad spectrum of anti-tumor activities has been reported for phenanthroindolizidine alkaloids (PAs), however, their mode of action in TNBC remains elusive. Thus, we investigated six naturally occurring PAs extracted from the plant Tylophora ovata: O-methyltylophorinidine (1) and its five derivatives tylophorinidine (2), tylophoridicine E (3), 2-demethoxytylophorine (4), tylophoridicine D (5), and anhydrodehydrotylophorinidine (6). In comparison to natural (1) and for more-in depth studies, we also utilized a sample of synthetic O-methyltylophorinidine (1s). Our results indicate a remarkably effective blockade of nuclear factor kappa B (NF kappa B) within 2 h for compounds (1) and (1s) (IC50 = 17.1 +/- 2.0 nM and 3.3 +/- 0.2 nM) that is different from its effect on cell viability within 24 h (IC50 = 13.6 +/- 0.4 nM and 4.2 +/- 1 nM). Furthermore, NF kappa B inhibition data for the additional five analogues indicate a structure-activity relationship (SAR). Mechanistically, NF kappa B is significantly blocked through the stabilization of its inhibitor protein kappa B alpha (I kappa B alpha) under normoxic as well as hypoxic conditions. To better mimic the TNBC microenvironment in vitro, we established a 3D co-culture by combining the human TNBC cell line MDA-MB-231 with primary murine cancer-associated fibroblasts (CAF) and type I collagen. Compound (1) demonstrates superiority against the therapeutic gold standard paclitaxel by diminishing spheroid growth by 40% at 100 nM. The anti-proliferative effect of (1s) is distinct from paclitaxel in that it arrests the cell cycle at the G0/G1 state, thereby mediating a time-dependent delay in cell cycle progression. Furthermore, (1s) inhibited invasion of TNBC monoculture spheroids into a matrigel (R)-based environment at 10 nM. In conclusion, PAs serve as promising agents with presumably multiple target sites to combat inflammatory and hypoxia-driven cancer, such as TNBC, with a different mode of action than the currently applied chemotherapeutic drugs.

[16] An organometallic analogue of combretastatin A-4 and its apoptosis-inducing effects on lymphoma, leukemia and other tumor cells in vitro

L. A. Onambele, N. Hoffmann, L. Kater, L. Hemmersbach, J. M. Neudörfl, N. Sitnikov, B. Kater, C. Frias, H. G. Schmalz, A. Prokop, RSC Med. Chem. 2022, 13, 1044-1051. DOI: https://www.doi.org/10.1039/d2md00144f

Abstract

Hexacarbonyl[1,3-dimethoxy-5-((4 '-methoxyphenyl)ethynyl)benzene]dicobalt (NAHO27), an organometallic analogue of combretastatin A-4, has been synthesized and its activity against lymphoma, leukemia, breast cancer and melanoma cells has been investigated. It was shown that NAHO27 specifically induces apoptosis in BJAB lymphoma and Nalm-6 leukemia cells at low micromolar concentration and does not affect normal leukocytes in vitro. It also proved to be active against vincristine and daunorubicin resistant leukemia cell lines with p-glycoprotein-caused multidrug resistance and showed a pronounced (550%) synergistic effect when co-applied with vincristine at very low concentrations. Mechanistic investigations revealed NAHO27 to induce apoptosis via the mitochondrial (intrinsic) pathway as reflected by the processing of caspases 3 and 9, the involvement of Bcl-2 and smac/DIABLO, and the reduction of mitochondrial membrane potential. Gene expression analysis and protein expression analysis via western blot showed an upregulation of the proapoptotic protein harakiri by 9%.

[17] Head-to-Head Comparison of Selected Extra- and Intracellular CO-Releasing Molecules on Their CO-Releasing and Anti-Inflammatory Properties

Y. C. Li, L. Hemmersbach, B. Krause, N. Sitnikov, A. S. N. Göderz, D. O. P. Maldonado, H. G. Schmalz, B. Yard, ChemBioChem 2022, 23, 9. DOI: https://www.doi.org/10.1002/cbic.202100452

Abstract

Over the past decade, a variety of carbon monoxide releasing molecules (CORMs) have been developed and tested. Some CORMs spontaneously release CO once in solution, while others require a trigger mechanism to release the bound CO from its molecular complex. The modulation of biological systems by CORMs depends largely on the spatiotemporal release of CO, which likely differs among the different types of CORMs. In spontaneously releasing CORMs, CO is released extracellularly and crosses the cell membrane to interact with intracellular targets. Other CORMs can directly release CO intracellularly, which may be a more efficient method to modulate biological systems. In the present study, we compared the efficacy of extracellular and intracellular CO-releasing CORMs that either release CO spontaneously or require an enzymatic trigger. The efficacy of such CORMs to modulate HO-1 and VCAM-1 expression in TNF-alpha-stimulated human umbilical vein endothelial cells (HUVEC) was evaluated.

[18] Design and synthesis of a tetracyclic tripeptide mimetic frozen in a polyproline type II (PP2) helix conformation

M. T. Klein, B. M. Krause, J. M. Neudörfl, R. Kühne, H. G. Schmalz, Org. Biomol. Chem. 2022, 20, 9368-9377. DOI: https://www.doi.org/10.1039/d2ob01857h

Abstract

A synthesis of the new tetracyclic scaffold ProM-19, which represents a XPP tripeptide unit frozen in a PPII helix conformation, was developed. As a key building block, N-Boc-protected ethyl (1S,3S,4R)-2-azabicyclo[2.2.1]hept-5-ene-2-carboxylate was prepared through a diastereoselective aza-Diels-Alder reaction and subsequent hydrogenolytic removal of the chiral N-1-phenylethyl substituent under temporary protection of the double bond through dihydroxylation and reconstitution by Corey-Winter olefination. The target compound Boc-[ProM-19]-OMe was then prepared via subsequent peptide coupling and Ru-catalyzed ring-closing metathesis steps employing (S)-N-Boc-allylgylcine and cis-5-vinyl-proline methyl ester as additional building blocks. In addition, Ac-[2-Cl-Phe]-[Pro]-[ProM-19]-OMe was prepared by solution phase peptide synthesis as a potential ligand for the ena-VASP EVH1 domain.

[19] Synthesis and Biological Evaluation of Water-Soluble Esterase-Activated CO-Releasing Molecules Targeting Mitochondria

L. Hemmersbach, Y. Schreiner, X. M. Zhang, F. Dicke, L. Hünemeyer, J. M. Neudörfl, T. Fleming, B. Yard, H. G. Schmalz, Chem.-Eur. J. 2022, 28, 9. DOI: https://www.doi.org/10.1002/chem.202201670

Abstract

Due to the beneficial effects of carbon monoxide as a cell-protective and anti-inflammatory agent, CO-releasing molecules (CORMs) offer some promising potential applications in medicine. In this context, we synthesized a set of acyloxy-cyclohexadiene-Fe(CO)(3) complexes, all displaying a N-methyl-pyridinium triflate moiety in the ester side chain, as mitochondria-targeting esterase-triggered CORM prodrugs. Whereas the compounds in which the acyloxy substituent is attached to the 2-position of the diene-Fe(CO)(3) unit (A series) spontaneously release CO upon dissolution in phosphate buffer, which remarkably is partly suppressed in the presence of porcine liver esterase (PLE), the 1-substituted isomers (B series) show the expected PLE-induced release of CO (up to 3 equiv.). The biological activity of Mito-CORMs 2/3-B and their isophorone-derived analogs 2/3-A', which also displayed PLE-induced CO release, was assessed by using human umbilical vein endothelial cells (HUVEC). Whereas Mito-CORMs 2/3-B were not cytotoxic up to 500 mu M (MTT assay), Mito-CORMs 2/3-A' caused significant toxicity at concentrations above 50 mu M. The anti-inflammatory potential of both Mito-CORM variants was demonstrated by concentration-dependent down-regulation of the pro-inflammatory markers VCAM-1, ICAM-1 and CXCL1 as well as induction of HO-1 in TNF alpha-stimulated human umbilical vein endothelial cells (HUVECs; western blotting and qPCR). Energy phenotyping by seahorse real-time cell metabolic analysis, revealed opposing shifts of metabolic potentials in cells treated either with Mito-CORMs 2/3-B (increased mitochondrial respiration and glycolytic activity) or Mito-CORMs 2/3-A' (suppressed mitochondrial respiration and increased glycolytic activity). Thus, the Mito-CORMs represent valuable tools for the safe and targeted delivery of CO to mitochondria as a subcellular compartment to induce positive anti-inflammatory effects with only minor shifts in cellular energy metabolism. Also, due to their water solubility, these compounds provide a promising starting point for further pharmacological studies.

[20] Vinylogous Winstein Rearrangement: Unexpected Isomerization of an Azide-Substituted Cyclohexadiene-Fe(CO)3 Complex

A. S. N. Göderz, L. Hemmersbach, S. Romanski, J. M. Neudörfl, H. G. Schmalz, Organometallics 2022, 41, 2997-3003. DOI: https://www.doi.org/10.1021/acs.organomet.2c00418

Abstract

In the course of our research into enzyme-triggered CO-releasing molecules (ET-CORMs), we were interested in using 2-acetoxy-5-azido-1,3-cyclohexadiene-Fe(CO)3 (rac-2) as a building block for further structural modification by means of Cu -catalyzed azide-alkyne cycloaddition (CuAAC click chemistry). Treatment of [2-acetoxy-cyclohexadienyl-Fe(CO)3]+[PF6]- with Zn(N3)2, TMS-N3, or NaN3 surprisingly afforded 2-acetoxy-1-azido-2,4-cyclohexadiene-Fe(CO)3 (rac-9) as the main product. We could show that rac-2 is primarily formed under kinetic control but undergoes a rapid isomerization to rac-9 (as the thermodynamic product) in a formal vinylogous Winstein rearrangement under concomitant migration of the Fe(CO)3 moiety. This unprecedented reaction displays a 1st order kinetics and appears to proceed via an ionic (rather than a concerted intramolecular) mechanism as supported by crossover experiments using deuterated compounds. The CuAAC reaction of rac-9 with propargylic alcohol afforded triazole rac-13, which was demonstrated (by headspace-gas chromatography (GC)) to act as an ET-CORM in the presence of porcine liver esterase.

[21] Synthetic α-Helical Peptides as Potential Inhibitors of the ACE2 SARS-CoV-2 Interaction

P. M. Engelhardt, S. Florez-Rueda, M. Drexelius, J. M. Neudörfl, D. Lauster, C. P. R. Hackenberger, R. Kühne, I. Neundorf, H. G. Schmalz, ChemBioChem 2022, 23, 6. DOI: https://www.doi.org/10.1002/cbic.202200372

Abstract

During viral cell entry, the spike protein of SARS-CoV-2 binds to the alpha 1-helix motif of human angiotensin-converting enzyme 2 (ACE2). Thus, alpha-helical peptides mimicking this motif may serve as inhibitors of viral cell entry. For this purpose, we employed the rigidified diproline-derived module ProM-5 to induce alpha-helicity in short peptide sequences inspired by the ACE2 alpha 1-helix. Starting with Ac-QAKTFLDKFNHEAEDLFYQ-NH2 as a relevant section of alpha 1, a series of peptides, N-capped with either Ac-beta HAsp-[ProM-5] or Ac-beta HAsp-PP, were prepared and their alpha-helicities were investigated. While ProM-5 clearly showed a pronounced effect, an even increased degree of helicity (up to 63 %) was observed in sequences in which non-binding amino acids were replaced by alanine. The binding affinities of the peptides towards the spike protein, as determined by means of microscale thermophoresis (MST), revealed only a subtle influence of the alpha-helical content and, noteworthy, led to the identification of an Ac-beta HAsp-PP-capped peptide displaying a very strong binding affinity (K-D=62 nM).

[22] On the Asymmetric Iridium-Catalyzed N-Allylation of Amino Acid Esters: Improved Selectivities through Structural Variation of the Chiral Phosphoramidite Ligand

D. Albat, A. Köcher, J. Witt, H. G. Schmalz, Eur. J. Org. Chem. 2022, 2022, 6. DOI: https://www.doi.org/10.1002/ejoc.202200188

Abstract

The investigation of the iridium-catalyzed asymmetric N-allylation of tert-butyl glycinate using a "branched" racemic 1-vinyl-alkyl methyl carbonate revealed severe limitations of existing protocols. By screening a set of 24 BINOL-derived chiral phosphoramidites a new superior ligand (L24*) was identified which afforded the amination product with high enantioselectivity (>= 9 5 % ee) under optimized conditions. This ligand also allowed the N-allylation of other amino acid tert-butyl esters (derived from alanine, phenylalanine, or proline) with out-standing levels of diastereocontrol (d.r. 99:1) and negligible matched/mismatched differences.

 

Publications

[23] ET-CORM Mediated Vasorelaxation of Small Mesenteric Arteries: Involvement of Kv7 Potassium Channels, D. F. Zhang, B. M. Krause, H. G. Schmalz, P. Wohlfart, B. A. Yard, R. Schubert, Front. Pharmacol. 2021, 12, 11. DOI: https://www.doi.org/10.3389/fphar.2021.702392

[24] A Concise Synthesis of 24,25-Dihydro-6-epi-Monanchosterol A, O. Taspinar, V. K. Stojadinovic, J. M. Neudoerfl, H. G. Schmalz, Synlett 2021, 32, 1085-1088. DOI: https://www.doi.org/10.1055/a-1480-5225

[25] Some Surprising Transformations of Colchicone and Other Colchicine-Derived Tropolones, A. Stein, P. H. N. Thomopoulou, T. Schulte, J. Neudörfl, M. Breugst, H. G. Schmalz, Eur. J. Org. Chem. 2021, 2021, 6375-6382. DOI: https://www.doi.org/10.1002/ejoc.202100999

[26] Enantioselective Cleavage of Cyclobutanols Through Ir-Catalyzed C-C Bond Activation: Mechanistic and Synthetic Aspects, F. Ratsch, J. P. Strache, W. Schlundt, J. M. Neudörfl, A. Adler, S. Aziz, B. Goldfuss, H. G. Schmalz, Chem.-Eur. J. 2021, 27, 4640-4652. DOI: https://www.doi.org/10.1002/chem.202004843

[27] Total Synthesis of (+)-Erogorgiaene and the Pseudopterosin A-F Aglycone via Enantioselective Cobalt-Catalyzed Hydrovinylation, S. Movahhed, J. Westphal, A. Kempa, C. E. Schumacher, J. Sperlich, J. M. Neudörfl, N. Teusch, M. Hochgürtel, H. G. Schmalz, Chem.-Eur. J. 2021, 27, 11574-11579. DOI: https://www.doi.org/10.1002/chem.202101863

[28] ItaCORMs: conjugation with a CO-releasing unit greatly enhances the anti-inflammatory activity of itaconates, B. M. Krause, B. Bauer, J. M. Neudörfl, T. Wieder, H. G. Schmalz, RSC Med. Chem. 2021, 12, 2053-2059. DOI: https://www.doi.org/10.1039/d1md00163a

[29] On the Diastereoselectivity of the Complexation of Ketopinic Acid-Derived 2-Acyloxy-1,3-cyclohexadienes and the Configurational Stability of Dienol-Fe(CO)3 Complexes. A Case Study, L. Hemmersbach, S. Romanski, S. Botov, A. Adler, J. M. Neudörfl, H. G. Schmalz, Organometallics 2021, 40, 2909-2914. DOI: https://www.doi.org/10.1021/acs.organomet.1c00354

[30] Scalable Synthesis of N,N′Di(2,3-dihydroxy-propyl)-1,4-naphthalenedipropanamide and Its 1,4-Endoperoxide as a Singlet Oxygen-Releasing Molecule, M. Gemki, Ö. Taspinar, A. Adler, A. G. Griesbeck, D. Gründemann, H. G. Schmalz, Org. Process Res. Dev. 2021, 25, 2747-2753. DOI: https://www.doi.org/10.1021/acs.oprd.1c00364

[31] Enantioselective Total Synthesis and Structural Revision of Dysiherbol A, J. Baars, I. Grimm, D. Blunk, J. M. Neudörfl, H. G. Schmalz, Angew. Chem.-Int. Edit. 2021, 60, 14915-14920. DOI: https://www.doi.org/10.1002/anie.202105733

[32] Improved Synthesis of MediPhos Ligands and Their Use in the Pd-Catalyzed Enantioselective N-Allylation of Glycine Esters, D. Albat, M. Reiher, J. M. Neudörfl, H. G. Schmalz, Eur. J. Org. Chem. 2021, 2021, 4237-4242. DOI: https://www.doi.org/10.1002/ejoc.202100748

[33] A Short Enantioselective Synthesis of (S)-Levetiracetam through Direct Palladium-Catalyzed Asymmetric N-Allylation of Methyl 4-Aminobutyrate, D. Albat, J. M. Neudörfl, H. G. Schmalz, Synlett 2021, 32, 1089-1092. DOI: https://www.doi.org/10.1055/a-1493-9078

[34] A General Stereocontrolled Synthesis of Opines through Asymmetric Pd-Catalyzed N-Allylation of Amino Acid Esters, D. Albat, J. M. Neudoerfl, H. G. Schmalz, Eur. J. Org. Chem. 2021, 2021, 2099-2102. DOI: https://www.doi.org/10.1002/ejoc.202100259

[35] Synthesis of the 8,19-Epoxysteroid Eurysterol A, Ö. Taspinar, T. Wilczek, J. Erver, M. Breugst, J. M. Neudörfl, H. G. Schmalz, Chem.-Eur. J. 2020, 26, 4256-4260. DOI: https://www.doi.org/10.1002/chem.202000585

[36] Triple-Helix-Stabilizing Effects in Collagen Model Peptides Containing PPII-Helix-Preorganized Diproline Modules, A. Maassen, J. M. Gebauer, E. T. Abraham, I. Grimm, J. M. Neudörfl, R. Kühne, I. Neundorf, U. Baumann, H. G. Schmalz, Angew. Chem.-Int. Edit. 2020, 59, 5747-5755. DOI: https://www.doi.org/10.1002/anie.201914101

[37] Colchicine Alkaloids and Synthetic Analogues: Current Progress and Perspectives, I. A. Gracheva, E. S. Shchegravina, H. G. Schmalz, I. P. Beletskaya, A. Y. Fedorov, J. Med. Chem. 2020, 63, 10618-10651. DOI: https://www.doi.org/10.1021/acs.jmedchem.0c00222

[38] Pd-Catalyzed Asymmetric N-Allylation of Amino Acid Esters with Exceptional Levels of Catalyst Control: Stereo-Divergent Synthesis of ProM-15 and Related Bicyclic Dipeptide Mimetics, S. Dohmen, M. Reiher, D. Albat, S. Akyol, M. Barone, J. M. Neudörfl, R. Kühne, H. G. Schmalz, Chem.-Eur. J. 2020, 26, 3049-3053. DOI: https://www.doi.org/10.1002/chem.202000307

[39] Designed nanomolar small-molecule inhibitors of Ena/VASP EVH1 interaction impair invasion and extravasation of breast cancer cells, M. Barone, M. Müller, S. Chiha, J. Ren, D. Albat, A. Soicke, S. Dohmen, M. Klein, J. Bruns, M. van Dinther, R. Opitz, P. Lindemann, M. Beerbaum, K. Motzny, Y. Roske, P. Schmieder, R. Volkmer, M. Nazaré, U. Heinemann, H. Oschkinat, P. ten Dijke, H. G. Schmalz, R. Kühne, Proc. Natl. Acad. Sci. U. S. A. 2020, 117, 29684-29690. DOI: https://www.doi.org/10.1073/pnas.2007213117

[40] Design and Synthesis of New Protease-Triggered CO-Releasing Peptide-Metal-Complex Conjugates, N. S. Sitnikov, Y. B. Malysheva, A. Y. Fedorov, H. G. Schmalz, Eur. J. Org. Chem. 2019, 2019, 6830-6837. DOI: https://www.doi.org/10.1002/ejoc.201901206

[41] A Facile Synthetic Approach to Nonracemic Substituted Pyrrolo-allocolchicinoids Starting from Natural Colchicine, E. S. Shchegravina, E. V. Svirshchevskaya, H. G. Schmalz, A. Y. Fedorov, Synthesis 2019, 51, 1611-1622. DOI: https://www.doi.org/10.1055/s-0037-1610673

[42] The Science Forum in Aachen: Joyful Expectations, H. G. Schmalz, ChemKon 2019, 26, 177-177. DOI: https://www.doi.org/10.1002/ckon.201900048

[43] Total Synthesis of α-Tocopherol through Enantioselective Iridium-Catalyzed Fragmentation of a Spiro-Cyclobutanol Intermediate, F. Ratsch, W. Schlundt, D. Albat, A. Zimmer, J. M. Neudörfl, T. Netscher, H. G. Schmalz, Chem.-Eur. J. 2019, 25, 4941-4945. DOI: https://www.doi.org/10.1002/chem.201900564

[44] Regeneration of ergothioneine after reaction with singlet oxygen, M. Oumari, B. Goldfuss, C. Stoffels, H. G. Schmalz, D. Gründemann, Free Radic. Biol. Med. 2019, 134, 508-514. DOI: https://www.doi.org/10.1016/j.freeradbiomed.2019.01.043

[45] Inhibition of CPAP-tubulin interaction prevents proliferation of centrosome-amplified cancer cells, A. Mariappan, K. Soni, K. Schorpp, F. Zhao, A. Minakar, X. D. Zheng, S. Mandad, I. Macheleidt, A. Ramani, T. Kubelka, M. Dawidowski, K. Golfmann, A. Wason, C. H. Yang, J. Simons, H. G. Schmalz, A. A. Hyman, R. Aneja, R. Ullrich, H. Urlaub, M. Odenthal, R. Büttner, H. T. Li, M. Sattler, K. Hadian, J. Gopalakrishnan, Embo J. 2019, 38, 24. DOI: https://www.doi.org/10.15252/embj.201899876

[46] Comment on Enantioselective total synthesis of (-)-colchicine, (+)-demecolcinone and metacolchicine: determination of the absolute configurations of the latter two alkaloids by B. Chen, X. Liu, Y.-J. Hu, D.-M. Zhang, L. Deng, J. Lu, L. Min, W.-C. Ye and C.-C. Li, Chem. Sci., 2017, 8, 4961-4966, R. W. Hoffmann, H. G. Schmalz, U. Koert, G. K. Pierens, Chem. Sci. 2019, 10, 943-945. DOI: https://www.doi.org/10.1039/c8sc90247j

[47] A Stereoselective Synthesis of the ACE Inhibitor Trandolapril, S. Chiha, M. Spilles, J. M. Neudörfl, H. G. Schmalz, Synlett 2019, 30, 813-816. DOI: https://www.doi.org/10.1055/s-0037-1612306

[48] A synthetic derivative of houttuynoid B prevents cell entry of Zika virus, M. Basic, F. Elgner, D. Bender, C. Sabino, M. L. Herrlein, H. Roth, M. Glitscher, A. Fath, T. Kerl, H. G. Schmalz, E. Hildt, Antiviral Res. 2019, 172, 12. DOI: https://www.doi.org/10.1016/j.antiviral.2019.104644

[49] Hydrogen Peroxide Sensors Based on Fluorescence Quenching of the 2-AminobenzimidazoleFluorophore, M. Atar, Ö. Taspinar, S. Hanft, B. Goldfuss, H. G. Schmalz, A. G. Griesbeck, J. Org. Chem. 2019, 84, 15972-15977. DOI: https://www.doi.org/10.1021/acs.joc.9b02262

[50] Synthetic Indolactam V Analogues as Inhibitors of PAR2-Induced Calcium Mobilization in Triple-Negative Breast Cancer Cells, J. Stein, S. Stahn, J. M. Neudörfl, J. Sperlich, H. G. Schmalz, N. Teusch, ChemMedChem 2018, 13, 147-154. DOI: https://www.doi.org/10.1002/cmdc.201700640

[51] Enantioselective transition metal catalysis using new modular chiral biphosphine-ligands, M. Reiher, H. G. Schmalz, Abstr. Pap. Am. Chem. Soc. 2018, 256, 1.

[52] An Atom-Economic and Stereospecific Access to Trisubstituted Olefins through Enyne Cross Metathesis Followed by 1,4-Hydrogenation, F. Ratsch, H. G. Schmalz, Synlett 2018, 29, 785-792. DOI: https://www.doi.org/10.1055/s-0036-1591528

[53] Chiral Phosphine-Phosphite Ligands in Asymmetric Gold Catalysis: Highly Enantioselective Synthesis of Furo 3,4-d -Tetrahydropyridazine Derivatives through 3+3 -Cycloaddition, Q. W. Du, J. M. Neudörfl, H. G. Schmalz, Chem.-Eur. J. 2018, 24, 2379-2383. DOI: https://www.doi.org/10.1002/chem.201800042

[54] Design and Synthesis of Building Blocks for PPII-Helix Secondary-Structure Mimetics: A Stereoselective Entry to 4-Substituted 5-Vinylprolines, S. Chiha, A. Soicke, M. Barone, M. Müller, J. Bruns, R. Opitz, J. M. Neudörfl, R. Kühne, H. G. Schmalz, Eur. J. Org. Chem. 2018, 2018, 455-460. DOI: https://www.doi.org/10.1002/ejoc.201701584

[55] Design and Synthesis of Building Blocks for PPII-Helix Secondary-Structure Mimetics: A Stereoselective Entry to 4-Substituted 5-Vinylprolines (vol 2018, pg 455, 2018), S. Chiha, A. Soicke, M. Barone, M. Müller, J. Bruns, R. Opitz, J. M. Neudörfl, R. Kühne, H. G. Schmalz, Eur. J. Org. Chem. 2018, 2018, 6597-6597. DOI: https://www.doi.org/10.1002/ejoc.201801732

[56] Ergothioneine stands out from hercynine in the reaction with singlet oxygen: Resistance to glutathione and TRIS in the generation of specific products indicates high reactivity, C. Stoffels, M. Oumari, A. Perrou, A. Termath, W. Schlundt, H. G. Schmalz, M. Schäfer, V. Wewer, S. Metzger, E. Schömig, D. Gründemann, Free Radic. Biol. Med. 2017, 113, 385-394. DOI: https://www.doi.org/10.1016/j.freeradbiomed.2017.10.372

[57] Synthesis and biological evaluation of novel non-racemic indole-containing allocolchicinoids, E. S. Shchegravina, A. A. Maleev, S. K. Ignatov, I. A. Gracheva, A. Stein, H. G. Schmalz, A. E. Gavryushin, A. A. Zubareva, E. V. Svirshchevskaya, A. Y. Fedorov, Eur. J. Med. Chem. 2017, 141, 51-60. DOI: https://www.doi.org/10.1016/j.ejmech.2017.09.055

[58] Tandem Hydroalumination/Cu-Catalyzed Asymmetric Vinyl Metalation as a New Access to Enantioenriched Vinylcyclopropane Derivatives, D. S. Müller, V. Werner, S. Akyol, H. G. Schmalz, I. Marek, Org. Lett. 2017, 19, 3970-3973. DOI: https://www.doi.org/10.1021/acs.orglett.7b01661

[59] Synthesis and cytostatic properties of polyfunctionalized furanoallocolchicinoids, I. A. Gracheva, I. V. Voitovich, V. I. Faerman, N. S. Sitnikov, E. V. Myrsikova, H. G. Schmalz, E. V. Svirshevskaya, A. Y. Fedorov, Eur. J. Med. Chem. 2017, 126, 432-443. DOI: https://www.doi.org/10.1016/j.ejmech.2016.11.020

[60] Organocatalyzed Synthesis of Oleochemical Carbonates from CO2 and Renewables, H. Büttner, J. Steinbauer, C. Wulf, M. Dindaroglu, H. G. Schmalz, T. Werner, ChemSusChem 2017, 10, 1076-1079. DOI: https://www.doi.org/10.1002/cssc.201601163

[61] Methyl Fumarate-Derived Iron Carbonyl Complexes (FumET-CORMs) as Powerful Anti-inflammatory Agents, B. Bauer, A. L. Göderz, H. Braumüller, J. M. Neudörfl, M. Röcken, T. Wieder, H. G. Schmalz, ChemMedChem 2017, 12, 1927-1930. DOI: https://www.doi.org/10.1002/cmdc.201700488

[62] New Colchicine-Derived Triazoles and Their Influence on Cytotoxicity and Microtubule Morphology, P. Thomopoulou, J. Sachs, N. Teusch, A. Mariappan, J. Gopalakrishnan, H. G. Schmalz, ACS Med. Chem. Lett. 2016, 7, 188-191. DOI: https://www.doi.org/10.1021/acsmedchemlett.5b00418

[63] Prevention of colitis by controlled oral drug delivery of carbon monoxide, C. Steiger, K. Uchiyama, T. Takagi, K. Mizushima, Y. Higashimura, M. Gutmann, C. Hermann, S. Botov, H. G. Schmalz, Y. Naito, L. Meinel, J. Control. Release 2016, 239, 128-136. DOI: https://www.doi.org/10.1016/j.jconrel.2016.08.030

[64] Synthesis of Nonracemic Pyrrolo-allocolchicinoids Exhibiting Potent Cytotoxic Activity, E. S. Shchegravina, D. I. Knyazev, I. P. Beletskaya, E. V. Svirshchevskaya, H. G. Schmalz, A. Y. Fedorov, Eur. J. Org. Chem. 2016, 2016, 5620-5623. DOI: https://www.doi.org/10.1002/ejoc.201601069

[65] CHEMISTRY A molecular shuttle for hydrogen cyanide, H. G. Schmalz, Science 2016, 351, 817-817. DOI: https://www.doi.org/10.1126/science.aaf2215

[66] Low-Pressure Cobalt-Catalyzed Enantioselective Hydrovinylation of Vinylarenes, S. Movahhed, J. Westphal, M. Dindaroglu, A. Falk, H. G. Schmalz, Chem.-Eur. J. 2016, 22, 7381-7384. DOI: https://www.doi.org/10.1002/chem.201601283

[67] Total Synthesis of the Antiviral Natural Product Houttuynoid B, T. Kerl, F. Berger, H. G. Schmalz, Chem.-Eur. J. 2016, 22, 2935-2938. DOI: https://www.doi.org/10.1002/chem.201505118

[68] A fast and simple LC-MS-based characterization of the flavonoid biosynthesis pathway for few seed(ling)s, B. Jaegle, M. K. Uroic, X. Holtkotte, C. Lucas, A. O. Termath, H. G. Schmalz, M. Bucher, U. Hoecker, M. Hülskamp, A. Schrader, BMC Plant Biol. 2016, 16, 15. DOI: https://www.doi.org/10.1186/s12870-016-0880-7

[69] Synthesis of New Sulfur-Containing Derivatives of Furanoallocolchicinoids, Y. A. Gracheva, H. G. Schmalz, E. V. Svirshchevskaya, A. Y. Fedorov, Russ. J. Organ. Chem. 2016, 52, 1137-1142. DOI: https://www.doi.org/10.1134/s1070428016080078

[70] Synthesis of Diverse 6-Oxa-allocolchicinoids by a Suzuki-Miyaura Coupling, Acid-Catalyzed Intramolecular Transacetalization Strategy, D. B. Yadav, L. Taleli, A. E. van der Westhuyzen, M. A. Fernandes, M. Dragoun, A. Prokop, H. G. Schmalz, C. B. de Koning, W. A. L. van Otterlo, Eur. J. Org. Chem. 2015, 2015, 5167-5182. DOI: https://www.doi.org/10.1002/ejoc.201500573

[71] Synthesis and Biological Evaluation of Furanoallocolchicinoids, Y. V. Voitovich, E. S. Shegravina, N. S. Sitnikov, V. I. Faerman, V. V. Fokin, H. G. Schmalz, S. Combes, D. Allegro, P. Barbier, I. P. Beletskaya, E. V. Svirshchevskaya, A. Y. Fedorov, J. Med. Chem. 2015, 58, 692-704. DOI: https://www.doi.org/10.1021/jm501678w

[72] Synthesis of indole-derived allocolchicine congeners exhibiting pronounced anti-proliferative and apoptosis-inducing properties, N. S. Sitnikov, A. V. Sinzov, D. Allegro, P. Barbier, S. Combes, L. A. Onambele, A. Prokop, H. G. Schmalz, A. Y. Fedorov, MedChemComm 2015, 6, 2158-2162. DOI: https://www.doi.org/10.1039/c5md00320b

[73] Synthesis and antitumor activity of 7-(triazol-1-yl)pyrroloallocolchicine derivatives, N. S. Sitnikov, A. V. Sintsov, E. S. Shchegravina, A. Prokop, H. G. Schmalz, V. V. Fokin, A. Y. Fedorov, Russ. Chem. Bull. 2015, 64, 1362-1368. DOI: https://www.doi.org/10.1007/s11172-015-1018-z

[74] Design, Synthesis, and Functional Evaluation of CO-Releasing Molecules Triggered by Penicillin G Amidase as a Model Protease, N. S. Sitnikov, Y. C. Li, D. F. Zhang, B. Yard, H. G. Schmalz, Angew. Chem.-Int. Edit. 2015, 54, 12314-12318. DOI: https://www.doi.org/10.1002/anie.201502445

[75] Design and Stereoselective Synthesis of ProM-2: A Spirocyclic Diproline Mimetic with Polyproline Type II (PPII) Helix Conformation, C. Reuter, R. Opitz, A. Soicke, S. Dohmen, M. Barone, S. Chiha, M. T. Klein, J. M. Neudörfl, R. Kühne, H. G. Schmalz, Chem.-Eur. J. 2015, 21, 8464-8470. DOI: https://www.doi.org/10.1002/chem.201406493

[76] Organometallic nucleosides induce non-classical leukemic cell death that is mitochondrial-ROS dependent and facilitated by TCL1-oncogene burden, C. Prinz, E. Vasyutina, G. Lohmann, A. Schrader, S. Romanski, C. Hirschhäuser, P. Mayer, C. Frias, C. D. Herling, M. Hallek, H. G. Schmalz, A. Prokop, D. Mougiakakos, M. Herling, Mol. Cancer 2015, 14, 18. DOI: https://www.doi.org/10.1186/s12943-015-0378-1

[77] A modular toolkit to inhibit proline-rich motif-mediated protein-protein interactions, R. Opitz, M. Müller, C. Reuter, M. Barone, A. Soicke, Y. Roske, K. Piotukh, P. Huy, M. Beerbaum, B. Wiesner, M. Beyermann, P. Schmieder, C. Freund, R. Volkmer, H. Oschkinat, H. G. Schmalz, R. Kühne, Proc. Natl. Acad. Sci. U. S. A. 2015, 112, 5011-5016. DOI: https://www.doi.org/10.1073/pnas.1422054112

[78] Synthesis of Chlorin-(Arylamino)quinazoline Hybrids as Models for Multifunctional Drug Development, A. V. Nyuchev, V. F. Otvagin, A. E. Gavryushin, Y. I. Romanenko, O. I. Koifman, D. V. Belykh, H. G. Schmalz, A. Y. Fedorov, Synthesis 2015, 47, 3717-3726. DOI: https://www.doi.org/10.1055/s-0034-1378876

[79] Individual steps of the Mizoroki-Heck reaction and intrinsic reactivity of intermediate organopalladium complexes studied in the gas phase, L. Fiebig, J. Held, H. G. Schmalz, M. Schäfer, Eur. J. Mass Spectrom. 2015, 21, 623-633. DOI: https://www.doi.org/10.1255/ejms.1310

[80] Enantioselective Nickel-Catalyzed Hydrocyanation using Chiral Phosphine-Phosphite Ligands: Recent Improvements and Insights, A. Falk, A. Cavalieri, G. S. Nichol, D. Vogt, H. G. Schmalz, Adv. Synth. Catal. 2015, 357, 3317-3320. DOI: https://www.doi.org/10.1002/adsc.201500644

[81] Biomimetic Synthesis of Isoindolinones Related to the Marilines, D. Augner, H. G. Schmalz, Synlett 2015, 26, 1395-1397. DOI: https://www.doi.org/10.1055/s-0034-1380700

[82] Total Synthesis of (2RS)-alpha-Tocopherol through Ni-Catalyzed 1,4-Addition to a Chromenone Intermediate, A. O. Termath, J. Velder, R. T. Stemmler, T. Netscher, W. Bonrath, H. G. Schmalz, Eur. J. Org. Chem. 2014, 2014, 3337-3340. DOI: https://www.doi.org/10.1002/ejoc.201402240

[83] Total Synthesis of (R, R, R)-alpha-Tocopherol Through Asymmetric Cu-Catalyzed 1,4-Addition, A. O. Termath, H. Sebode, W. Schlundt, R. T. Stemmler, T. Netscher, W. Bonrath, H. G. Schmalz, Chem.-Eur. J. 2014, 20, 12051-12055. DOI: https://www.doi.org/10.1002/chem.201404379

[84] Different design of enzyme-triggered CO-releasing molecules (ET-CORMs) reveals quantitative differences in biological activities in terms of toxicity and inflammation, E. Stamellou, D. Storz, S. Botov, E. Ntasis, J. Wedel, S. Sollazzo, B. K. Krämer, W. van Son, M. Seelen, H. G. Schmalz, A. Schmidt, M. Hafner, B. A. Yard, Redox Biol. 2014, 2, 739-748. DOI: https://www.doi.org/10.1016/j.redox.2014.06.002

[85] Stereoselective Synthesis of Tricyclic Diproline Analogues that Mimic a PPII Helix: Structural Consequences of Ring-Size Variation, A. Soicke, C. Reuter, M. Winter, J. M. Neudörfl, N. Schlörer, R. Kühne, H. G. Schmalz, Eur. J. Org. Chem. 2014, 2014, 6467-6480. DOI: https://www.doi.org/10.1002/ejoc.201402737

[86] Synthesis of Indole-Derived Allocolchicine Congeners through Pd-Catalyzed Intramolecular C-H Arylation Reaction, N. S. Sitnikov, A. S. Kokisheva, G. K. Fukin, J. M. Neudörfl, H. Sutorius, A. Prokop, V. V. Fokin, H. G. Schmalz, A. Y. Fedorov, Eur. J. Org. Chem. 2014, 2014, 6481-6492. DOI: https://www.doi.org/10.1002/ejoc.201402850

[87] Enzyme-triggered CO-releasing molecules (ET-CORMs), H. G. Schmalz, J. Biol. Inorg. Chem. 2014, 19, S719-S719.

[88] Stereoselective Synthesis of Proline- Derived Dipeptide Scaffolds ( ProM-3 and ProM-7) Rigidified in a PPII Helix Conformation, C. Reuter, M. Kleczka, S. de Mazancourt, J. M. Neudörfl, R. Kühne, H. G. Schmalz, Eur. J. Org. Chem. 2014, 2014, 2664-2667. DOI: https://www.doi.org/10.1002/ejoc.201301875

[89] New modular manganese(I) tricarbonyl complexes as PhotoCORMs: in vitro detection of photoinduced carbon monoxide release using COP-1 as a fluorogenic switch-on probe, S. Pai, M. Hafftlang, G. Atongo, C. Nagel, J. Niesel, S. Botov, H. G. Schmalz, B. Yard, U. Schatzschneider, Dalton Trans. 2014, 43, 8664-8678. DOI: https://www.doi.org/10.1039/c4dt00254g

[90] Asymmetric catalytic arylation of ethyl glyoxylate using organoboron reagents and Rh(I)-phosphane and phosphane-phosphite catalysts, C. S. Marques, M. Dindaroglu, H. G. Schmalz, A. J. Burke, RSC Adv. 2014, 4, 6035-6041. DOI: https://www.doi.org/10.1039/c3ra47000h

[91] Aryl-Phenyl Scrambling in Intermediate Organopalladium Complexes: A Gas-Phase Study of the Mizoroki-Heck Reaction, L. Fiebig, N. Schlörer, H. G. Schmalz, M. Schäfer, Chem.-Eur. J. 2014, 20, 4906-4910. DOI: https://www.doi.org/10.1002/chem.201400115

[92] Synthesis of C2-Symmetric Bisphosphine Ligands from Tartaric Acid, and Their Performance in the Pd-Catalyzed AsymmetricO-Allylation of a Phenol, M. Dindaroglu, A. Dinçer, H. G. Schmalz, Eur. J. Org. Chem. 2014, 2014, 4315-4326. DOI: https://www.doi.org/10.1002/ejoc.201402326

[93] Structure-Activity Relationships of Novel 2-Benzyl-3-Phenylisoindolinones as Inhibitors of Cholesterol Esterase, M. Steinkrüger, D. Augner, T. Mielke, M. Gütschow, S. Herzig, H. G. Schmalz, M. Pietsch, Naunyn-Schmiedebergs Arch. Pharmacol. 2013, 386, S80-S80.

[94] ENZYME-TRIGGERED CO-RELEASING MOLECULES (ET-CORMS): EVALUATION OF BIOLOGICAL ACTIVITY IN RELATION TO THEIR STRUCTURE, E. Stamellou, S. Romanski, S. Amslinger, M. Hafner, B. Krämer, H. G. Schmalz, B. A. Yard, Transpl. Int. 2013, 26, 56-56.

[95] Identification and Kinetic Characterization of Novel Inhibitors of Human Cholesterol Esterase as Anti-Atherosclerotic Agents, M. Sheikh, M. Steinkrüger, D. Augner, M. Gütschow, S. Herzig, H. G. Schmalz, M. Pietsch, Naunyn-Schmiedebergs Arch. Pharmacol. 2013, 386, S78-S78.

[96] Enzyme-triggered CO-releasing molecules (ET-CORMs): Evaluation of biological activity in relation to their structure, S. Romanski, E. Stamellou, J. T. Jaraba, D. Storz, B. K. Krämer, M. Hafner, S. Amslinger, H. G. Schmalz, B. A. Yard, Free Radic. Biol. Med. 2013, 65, 78-88. DOI: https://www.doi.org/10.1016/j.freeradbiomed.2013.06.014

[97] Lipophilic prodrugs of a triazole-containing colchicine analogue in liposomes: Biological effects on human tumor cells, N. R. Kuznetsova, E. V. Svirshchevskaya, N. S. Sitnikov, L. Abodo, H. Sutorius, J. Zapke, J. Velder, P. Thomopoulou, H. Oschkinat, A. Prokop, H. G. Schmalz, A. Y. Fedorov, E. L. Vodovozova, Russ. J. Bioorg. Chem. 2013, 39, 543-552. DOI: https://www.doi.org/10.1134/s1068162013050105

[98] Nucleoside Analogues with a 1,3-Diene-Fe(CO)3 Substructure: Stereoselective Synthesis, Configurational Assignment, and Apoptosis-Inducing Activity, C. Hirschhäuser, J. Velcicky, D. Schlawe, E. Hessler, A. Majdalani, J. M. Neudörfl, A. Prokop, T. Wieder, H. G. Schmalz, Chem.-Eur. J. 2013, 19, 13017-13029. DOI: https://www.doi.org/10.1002/chem.201301672

[99] Efficient -Helix Induction in a Linear Peptide Chain by N-Capping with a ridged-tricyclic Diproline Analogue, V. Hack, C. Reuter, R. Opitz, P. Schmieder, M. Beyermann, J. M. Neudörfl, R. Kühne, H. G. Schmalz, Angew. Chem.-Int. Edit. 2013, 52, 9539-9543. DOI: https://www.doi.org/10.1002/anie.201302014

[100] Cobalt Catalysis in the Gas Phase: Experimental Characterization of Cobalt(I) Complexes as Intermediates in Regioselective Diels-Alder Reactions, L. Fiebig, J. Kuttner, G. Hilt, M. C. Schwarzer, G. Frenking, H. G. Schmalz, M. Schäfer, J. Org. Chem. 2013, 78, 10485-10493. DOI: https://www.doi.org/10.1021/jo402001g

[101] Enantioselective Nickel-Catalyzed Hydrocyanation of Vinylarenes Using Chiral Phosphine-Phosphite Ligands and TMS-CN as a Source of HCN, A. Falk, A. L. Göderz, H. G. Schmalz, Angew. Chem.-Int. Edit. 2013, 52, 1576-1580. DOI: https://www.doi.org/10.1002/anie.201208082

[102] A Scalable Synthesis of Chiral Modular Phosphine-Phosphite Ligands, M. Dindaroglu, A. Falk, H. G. Schmalz, Synthesis 2013, 45, 527-535. DOI: https://www.doi.org/10.1055/s-0032-1316847

[103] TARTROL-derived chiral phosphine-phosphite ligands and their performance in enantioselective Cu-catalyzed 1,4-addition reactions, M. Dindaroglu, S. Akyol, H. Simsir, J. M. Neudörfl, A. Burke, H. G. Schmalz, Tetrahedron-Asymmetry 2013, 24, 657-662. DOI: https://www.doi.org/10.1016/j.tetasy.2013.04.008

[104] Synthesis and Performance of Acyloxy-diene-Fe(CO)3 Complexes with Variable Chain Lengths as Enzyme-Triggered Carbon Monoxide-Releasing Molecules, S. Botov, E. Stamellou, S. Romanski, M. Guttentag, R. Alberto, J. M. Neudörfl, B. Yard, H. G. Schmalz, Organometallics 2013, 32, 3587-3594. DOI: https://www.doi.org/10.1021/om301233h

[105] On the Antibiotic and Antifungal Activity of Pestalone, Pestalachloride A, and Structurally Related Compounds, D. Augner, O. Krut, N. Slavov, D. C. Gerbino, H. G. Sahl, J. Benting, C. F. Nising, S. Hillebrand, M. Krönke, H. G. Schmalz, J. Nat. Prod. 2013, 76, 1519-1522. DOI: https://www.doi.org/10.1021/np400301d

[106] Synthesis of Oxa-B-Ring Analogs of Colchicine through Rh-Catalyzed Intramolecular 5+2 Cycloaddition, A. O. Termath, S. Ritter, M. König, D. P. Kranz, J. M. Neudörfl, A. Prokop, H. G. Schmalz, Eur. J. Org. Chem. 2012, 2012, 4501-4507. DOI: https://www.doi.org/10.1002/ejoc.201200677

[107] Enzyme-Triggered CO-Releasing Molecules (ET-CORMs): Structural Entities that Mediate Restricted Cell Specificity for CO Release, E. Stamellou, S. Romanski, S. Amslinger, M. Hafner, B. K. Kraemer, H. G. Schmalz, B. A. Yard, Transplantation 2012, 94, 1134-1134. DOI: https://www.doi.org/10.1097/00007890-201211271-02252

[108] Total Synthesis of Indole-Derived Allocolchicine Analogues Exhibiting Strong Apoptosis-Inducing Activity, N. Sitnikov, J. Velder, L. Abodo, N. Cuvelier, J. Neudörfl, A. Prokop, G. Krause, A. Y. Fedorov, H. G. Schmalz, Chem.-Eur. J. 2012, 18, 12096-12102. DOI: https://www.doi.org/10.1002/chem.201200083

[109] Hydrophenalene-Cr(CO)(3) complexes as anti-inflammatory agents based on specific inhibition of NOD2 signalling: a SAR study, A. Saiai, H. Bielig, J. Velder, J. M. Neudörfl, M. Menning, T. A. Kufer, H. G. Schmalz, MedChemComm 2012, 3, 1377-1385. DOI: https://www.doi.org/10.1039/c2md20221b

[110] Iron Dienylphosphate Tricarbonyl Complexes as Water-Soluble Enzyme-Triggered CO-Releasing Molecules (ET-CORMs), S. Romanski, H. Rücker, E. Stamellou, M. Guttentag, J. M. Neudörfl, R. Alberto, S. Amslinger, B. Yard, H. G. Schmalz, Organometallics 2012, 31, 5800-5809. DOI: https://www.doi.org/10.1021/om300359a

[111] Acyloxybutadiene tricarbonyl iron complexes as enzyme-triggered CO-releasing molecules (ET-CORMs): a structure-activity relationship study, S. Romanski, B. Kraus, M. Guttentag, W. Schlundt, H. Rücker, A. Adler, J. M. Neudörfl, R. Alberto, S. Amslinger, H. G. Schmalz, Dalton Trans. 2012, 41, 13862-13875. DOI: https://www.doi.org/10.1039/c2dt30662j

[112] Cu-Catalyzed Enantioselective 1,4-Additions of Aryl-Grignard Reagents to Cyclohexenone in the Presence of TADDOL-Derived Phosphane-Phosphite Ligands, Q. Naeemi, M. Dindaroglu, D. P. Kranz, J. Velder, H. G. Schmalz, Eur. J. Org. Chem. 2012, 2012, 1179-1185. DOI: https://www.doi.org/10.1002/ejoc.201101258

[113] An Enantioselective Total Synthesis of Helioporins C and E, W. Lölsberg, S. Werle, J. M. Neudörfl, H. G. Schmalz, Org. Lett. 2012, 14, 5996-5999. DOI: https://www.doi.org/10.1021/ol302898h

[114] Molecular Oxygen as a Redox Catalyst in Intramolecular Photocycloadditions of Coumarins, D. P. Kranz, A. G. Griesbeck, R. Alle, R. Perez-Ruiz, J. M. Neudörfl, K. Meerholz, H. G. Schmalz, Angew. Chem.-Int. Edit. 2012, 51, 6000-6004. DOI: https://www.doi.org/10.1002/anie.201201222

[115] Synthesis of B-Ring-Modified Steroids through BF3-Promoted Rearrangement/Substitution of 6β-Hydroxy-5,19-cyclosteroids, D. P. Kranz, S. Chiha, A. M. Z. Greffen, J. M. Neudörfl, H. G. Schmalz, Org. Lett. 2012, 14, 3692-3695. DOI: https://www.doi.org/10.1021/ol301532w

[116] A novel conjugate of a cell-penetrating peptide and a ferrocenyl amino acid: a potential electrochemical sensor for living cells?, J. Hoyer, A. Hunold, H. G. Schmalz, I. Neundorf, Dalton Trans. 2012, 41, 6396-6398. DOI: https://www.doi.org/10.1039/c2dt12211a

[117] Nucleophile- or Light-Induced Synthesis of 3-Substituted Phthalides from 2-Formylarylketones, D. C. Gerbino, D. Augner, N. Slavov, H. G. Schmalz, Org. Lett. 2012, 14, 2338-2341. DOI: https://www.doi.org/10.1021/ol300757m

[118] TADDOL-Based Phosphane-Phosphite Ligands in Enantioselective Cu-Catalyzed Grignard 1,4-Additions Followed by Mannich-Type Alkylations, M. Drusan, W. Lölsberg, A. Skvorcová, H. G. Schmalz, R. Sebesta, Eur. J. Org. Chem. 2012, 2012, 6285-6290. DOI: https://www.doi.org/10.1002/ejoc.201200729

[119] Ligand Control of the Cobalt-Catalysed 1,4-Hydrovinylation Reaction, M. Arndt, M. Dindaroglu, H. G. Schmalz, G. Hilt, Synthesis 2012, 44, 3534-3542. DOI: https://www.doi.org/10.1055/s-0032-1316796

[120] Palladium-Catalyzed Cyanomethylation of Aryl Halides through Domino Suzuki Coupling-Isoxazole Fragmentation, J. Velcicky, A. Soicke, R. Steiner, H. G. Schmalz, J. Am. Chem. Soc. 2011, 133, 6948-6951. DOI: https://www.doi.org/10.1021/ja201743j

[121] Metal-Free Intramolecular Carbonyl-Olefin Metathesis of ortho-Prenylaryl Ketones, A. Soicke, N. Slavov, J. M. Neudörfl, H. G. Schmalz, Synlett 2011, 2487-2490. DOI: https://www.doi.org/10.1055/s-0030-1260320

[122] Enantioselective Access to 3-Methylene-1H-indanol through Asymmetric Domino Allylstannylation-Heck Reaction, J. Schütte, S. T. Ye, H. G. Schmalz, Synlett 2011, 2725-2729. DOI: https://www.doi.org/10.1055/s-0031-1289539

[123] (RS)-Tricarbonyl (η(4)-1,3-diacetoxy-5,5-dimethylcyclohex a-1,3-diene) iron(0), S. Romanski, J. M. Neudörfl, H. G. Schmalz, Acta Crystallogr. Sect. E.-Crystallogr. Commun. 2011, 67, M1530-+. DOI: https://www.doi.org/10.1107/s1600536811041298

[124] Acyloxybutadiene-Iron Tricarbonyl Complexes as Enzyme-Triggered CO-Releasing Molecules (ET-CORMs) (vol 50, pg 2392, 2011), S. Romanski, B. Kraus, U. Schatzschneider, J. M. Neudörfl, S. Amslinger, H. G. Schmalz, Angew. Chem.-Int. Edit. 2011, 50, 1.

[125] Acyloxybutadiene Iron Tricarbonyl Complexes as Enzyme-Triggered CO-Releasing Molecules (ET-CORMs), S. Romanski, B. Kraus, U. Schatzschneider, J. M. Neudörfl, S. Amslinger, H. G. Schmalz, Angew. Chem.-Int. Edit. 2011, 50, 2392-2396. DOI: https://www.doi.org/10.1002/anie.201006598

[126] Exercises in Pyrrolidine Chemistry: Gram Scale Synthesis of a Pro-Pro Dipeptide Mimetic with a Polyproline Type II Helix Conformation, C. Reuter, P. Huy, J. M. Neudörfl, R. Kühne, H. G. Schmalz, Chem.-Eur. J. 2011, 17, 12037-12044. DOI: https://www.doi.org/10.1002/chem.201101704

[127] A CONVENIENT ENTRY TO NEW C-7-MODIFIED COLCHICINOIDS THROUGH AZIDE ALKYNE 3+2 CYCLOADDITION: APPLICATION OF RING-CONTRACTIVE REARRANGEMENTS, N. Nicolaus, J. Reball, N. Sitnikov, J. Velder, A. Termath, A. Y. Fedorov, H. G. Schmalz, Heterocycles 2011, 82, 1585-+. DOI: https://www.doi.org/10.3987/com-10-s(e)117

[128] Total Synthesis of cyclo-Mumbaistatin Analogues through Anionic Homo-Fries Rearrangement, S. Neufeind, N. Hülsken, J. M. Neudörfl, N. Schlörer, H. G. Schmalz, Chem.-Eur. J. 2011, 17, 2633-2641. DOI: https://www.doi.org/10.1002/chem.201003166

[129] Chiral phosphine-phosphite ligands in the enantioselective 1,4-addition of Grignard reagents to α,β-unsaturated carbonyl compounds, Q. Naeemi, T. Robert, D. P. Kranz, J. Velder, H. G. Schmalz, Tetrahedron-Asymmetry 2011, 22, 887-892. DOI: https://www.doi.org/10.1016/j.tetasy.2011.04.018

[130] Sn(OTf)(2) as an Effective Lewis Acid in Reactions of Cyclopropyl Ketones with Acetic Anhydride: Application in the Synthesis of a 19-Nor-B-homo Steroid, D. P. Kranz, A. M. Z. Greffen, S. El Sheikh, J. M. Neudörfl, H. G. Schmalz, Eur. J. Org. Chem. 2011, 2011, 2860-2866. DOI: https://www.doi.org/10.1002/ejoc.201100020

[131] Stereoselective Synthesis and Biological Evaluation of Ferrocene-Containing 5-Hydroxyeicosatetraenoic Acid Analogues, N. Kausch-Busies, J. M. Neudörfl, P. Wefelmeier, A. Prokop, H. Kühn, H. G. Schmalz, Eur. J. Org. Chem. 2011, 2011, 4634-4644. DOI: https://www.doi.org/10.1002/ejoc.201100003

[132] Synthesis and First Biological Evaluation of an Iron-Containing HETE Analogue, N. Kausch-Busies, B. Kater, J. M. Neudörfl, A. Prokop, H. G. Schmalz, Eur. J. Org. Chem. 2011, 2011, 1133-1139. DOI: https://www.doi.org/10.1002/ejoc.201001445

[133] Iron containing anti-tumoral agents: unexpected apoptosis-inducing activity of a ferrocene amino acid derivative, B. Kater, A. Hunold, H. G. Schmalz, L. Kater, B. Bonitzki, P. Jesse, A. Prokop, J. Cancer Res. Clin. Oncol. 2011, 137, 639-649. DOI: https://www.doi.org/10.1007/s00432-010-0924-6

[134] Practical One-Pot Double Functionalizations of Proline, P. Huy, H. G. Schmalz, Synthesis 2011, 954-960. DOI: https://www.doi.org/10.1055/s-0030-1258428

[135] A Practical Synthesis of Trans-3-Substituted Proline Derivatives through 1,4-Addition, P. Huy, J. M. Neudörfl, H. G. Schmalz, Org. Lett. 2011, 13, 216-219. DOI: https://www.doi.org/10.1021/ol102613z

[136] Heck coupling in the gas phase: Examination of the reaction mechanism by ion/molecule reactions and mass spectrometry, L. Fiebig, H. G. Schmalz, M. Schäfer, Int. J. Mass Spectrom. 2011, 308, 307-310. DOI: https://www.doi.org/10.1016/j.ijms.2011.07.013

[137] Rhodium-Catalyzed Enantioselective Intramolecular 4+2 Cycloaddition using a Chiral Phosphine-Phosphite Ligand: Importance of Microwave-Assisted Catalyst Conditioning, A. Falk, L. Fiebig, J. M. Neudörfl, A. Adler, H. G. Schmalz, Adv. Synth. Catal. 2011, 353, 3357-3362. DOI: https://www.doi.org/10.1002/adsc.201100658

[138] Paraoxonase-1 is a major determinant of clopidogrel efficacy, H. J. Bouman, E. Schömig, J. W. van Werkum, J. Velder, C. M. Hackeng, C. Hirschhäuser, C. Waldmann, H. G. Schmalz, J. M. ten Berg, D. Taubert, Nat. Med. 2011, 17, 110-U287. DOI: https://www.doi.org/10.1038/nm.2281

[139] Paraoxonase-1 is a major determinant of clopidogrel efficacy (vol 17, pg 110, 2011), H. J. Bouman, E. Schömig, J. W. van Werkum, J. Velder, C. M. Hackeng, C. Hirschhäuser, C. Waldmann, H. G. Schmalz, J. M. ten Berg, D. Taubert, Nat. Med. 2011, 17, 1153-1153. DOI: https://www.doi.org/10.1038/nm0911-1153c

[140] Paraoxonase-1 and clopidogrel efficacy reply, H. J. Bouman, E. Schömig, J. W. van Werkum, J. Velder, C. M. Hackeng, C. Hirschhäuser, C. Waldmann, H. G. Schmalz, J. M. ten Berg, D. Taubert, Nat. Med. 2011, 17, 1042-1044. DOI: https://www.doi.org/10.1038/nm.2469

[141] Cobalt-Catalyzed 1,4-Hydrobutadienylation of 1-Aryl-1,3-dienes with 2,3-Dimethyl-1,3-butadiene, M. A. Bohn, A. Schmidt, G. Hilt, M. Dindaroglu, H. G. Schmalz, Angew. Chem.-Int. Edit. 2011, 50, 9689-9693. DOI: https://www.doi.org/10.1002/anie.201103613

[142] N-Capping of Primary Amines with 2-Acyl-benzaldehydes To Give Isoindolinones, D. Augner, D. C. Gerbino, N. Slavov, J. M. Neudörfl, H. G. Schmalz, Org. Lett. 2011, 13, 5374-5377. DOI: https://www.doi.org/10.1021/ol202271k

[143] Gaining Absolute Control of the Regiochemistry in the Cobalt-Catalyzed 1,4-Hydrovinylation Reaction, M. Arndt, M. Dindaroglu, H. G. Schmalz, G. Hilt, Org. Lett. 2011, 13, 6236-6239. DOI: https://www.doi.org/10.1021/ol202696n

[144] Addressing Protein-Protein Interactions with Small Molecules: A Pro-Pro Dipeptide Mimic with a PPII Helix Conformation as a Module for the Synthesis of PRD-Binding Ligands, J. Zaminer, C. Brockmann, P. Huy, R. Opitz, C. Reuter, M. Beyermann, C. Freund, M. Müller, H. Oschkinat, R. Kühne, H. G. Schmalz, Angew. Chem.-Int. Edit. 2010, 49, 7111-7115. DOI: https://www.doi.org/10.1002/anie.201001739

[145] A Scalable Synthesis of (±)-2-Oxoclopidogrel, J. Velder, C. Hirschhäuser, C. Waldmann, D. Taubert, H. J. Bouman, H. G. Schmalz, Synlett 2010, 467-469. DOI: https://www.doi.org/10.1055/s-0029-1219177

[146] Total Synthesis of the Marine Antibiotic Pestalone and its Surprisingly Facile Conversion into Pestalalactone and Pestalachloride A, N. Slavov, J. Cvengros, J. M. Neudörfl, H. G. Schmalz, Angew. Chem.-Int. Edit. 2010, 49, 7588-7591. DOI: https://www.doi.org/10.1002/anie.201003755

[147] Asymmetric Hydroformylation Using Taddol-Based Chiral Phosphine-Phosphite Ligands, T. Robert, Z. Abiri, J. Wassenaar, A. J. Sandee, S. Romanski, J. M. Neudörfl, H. G. Schmalz, J. N. H. Reek, Organometallics 2010, 29, 478-483. DOI: https://www.doi.org/10.1021/om9009735

[148] Phenol-derived chiral phosphine-phosphite ligands in the rhodium-catalyzed enantioselective hydrogenation of functionalized olefins, T. Robert, Z. Abiri, A. J. Sandee, H. G. Schmalz, J. N. H. Reek, Tetrahedron-Asymmetry 2010, 21, 2671-2674. DOI: https://www.doi.org/10.1016/j.tetasy.2010.10.026

[149] Potassium (1-methoxycarbonyl-2-methylprop-2-en-2-ylidene)azinate, C. Reuter, J. M. Neudörfl, H. G. Schmalz, Acta Crystallogr. Sect. E.-Crystallogr. Commun. 2010, 66, M461-U1150. DOI: https://www.doi.org/10.1107/s1600536810010159

[150] Azides Derived from Colchicine and their Use in Library Synthesis: a Practical Entry to New Bioactive Derivatives of an Old Natural Drug, N. Nicolaus, J. Zapke, P. Riesterer, J. M. Neudörfl, A. Prokop, H. Oschkinat, H. G. Schmalz, ChemMedChem 2010, 5, 661-665. DOI: https://www.doi.org/10.1002/cmdc.201000063

[151] Synthesis of Novel Allocolchicine Analogues with a Pyridine C-Ring through Intermolecular Vollhardt Diyne-Nitrile Cyclotrimerization, N. Nicolaus, H. G. Schmalz, Synlett 2010, 2071-2074. DOI: https://www.doi.org/10.1055/s-0030-1258512

[152] Enantioselective Copper-Catalysed Allylic Alkylation of Cinnamyl Chlorides by Grignard Reagents using Chiral Phosphine-Phosphite Ligands, W. Loelsberg, S. Ye, H. G. Schmalz, Adv. Synth. Catal. 2010, 352, 2023-2031. DOI: https://www.doi.org/10.1002/adsc.201000213

[153] Stereospecificity of the Au(I)-catalyzed reaction of 1-alkynyl-bicyclo 4.1.0 -heptan-2-ones with nucleophiles, S. Labsch, S. Ye, A. Adler, J. M. Neudörfl, H. G. Schmalz, Tetrahedron-Asymmetry 2010, 21, 1745-1751. DOI: https://www.doi.org/10.1016/j.tetasy.2010.05.019

[154] New caspase-independent but ROS-dependent apoptosis pathways are targeted in melanoma cells by an iron-containing cytosine analogue, J. C. Franke, M. Plötz, A. Prokop, C. C. Geilen, H. G. Schmalz, J. Eberle, Biochem. Pharmacol. 2010, 79, 575-586. DOI: https://www.doi.org/10.1016/j.bcp.2009.09.022

[155] Induction of apoptosis in Melanoma cells a new caspase-independent but ROS-dependent signaling pathways, J. Eberle, J. C. Franke, M. Plötz, A. Prokop, C. C. Geilen, H. G. Schmalz, Onkologie 2010, 33, 145-145.

[156] Anti-inflammatory Arene-Chromium Complexes Acting as Specific Inhibitors of NOD2 Signalling, H. Bielig, J. Velder, A. Saiai, M. Menning, S. Meemboor, W. Kalka-Moll, M. Krönke, H. G. Schmalz, T. A. Kufer, ChemMedChem 2010, 5, 2065-2071. DOI: https://www.doi.org/10.1002/cmdc.201000320

[157] trans-1,2-Bis(3,5-dimethoxyphenyl)ethene, S. Ritter, J. M. Neudörfl, J. Velder, H. G. Schmalz, Acta Crystallogr. Sect. E.-Crystallogr. Commun. 2009, 65, O2150-U1997. DOI: https://www.doi.org/10.1107/s160053680903116x

[158] trans-Ethylenedi-p-phenylene diacetate, S. Ritter, J. M. Neudörfl, J. Velder, H. G. Schmalz, Acta Crystallogr. Sect. E.-Crystallogr. Commun. 2009, 65, O2229-U2693. DOI: https://www.doi.org/10.1107/s1600536809032620

[159] A 2+2+2 -Cycloaddition Approach toward 6-Oxa-allocolchicinoids with Apoptosis-inducing Activity, N. Nicolaus, S. Strauss, J. M. Neudörfl, A. Prokop, H. G. Schmalz, Org. Lett. 2009, 11, 341-344. DOI: https://www.doi.org/10.1021/ol802542c

[160] Stereoselective Synthesis of New Ferrocene-Derived Amino Acid Building Blocks, A. Hunold, I. Neundorf, P. James, J. Neudörfl, H. G. Schmalz, Eur. J. Org. Chem. 2009, 2009, 4429-4440. DOI: https://www.doi.org/10.1002/ejoc.200900552

[161] Introduction of Allyl and Prenyl Side-Chains into Aromatic Systems by Suzuki Cross-Coupling Reactions, D. C. Gerbino, S. D. Mandolesi, H. G. Schmalz, J. C. Podestá, Eur. J. Org. Chem. 2009, 2009, 3964-3972. DOI: https://www.doi.org/10.1002/ejoc.200900234

[162] Electrophilic Activation of Benzaldehydes through ortho Palladation: One-Pot Synthesis of 3-Methylene-indan-1-ols through a Domino Allylstannylation/Heck Reaction under Neutral Conditions, J. Cvengros, J. Schütte, N. Schlörer, J. Neudörfl, H. G. Schmalz, Angew. Chem.-Int. Edit. 2009, 48, 6148-6151. DOI: https://www.doi.org/10.1002/anie.200901837

[163] Modular synthesis of chiral phosphine-phosphite-ligands from phenolic precursors:: A new approach to bidentate chelate ligands exploiting a P-O to P-C migration rearrangement, J. Velder, T. Robert, I. Weidner, J. M. Neudörfl, J. Lex, H. G. Schmalz, Adv. Synth. Catal. 2008, 350, 1309-1315. DOI: https://www.doi.org/10.1002/adsc.200800146

[164] Enantioselective Cu-catalyzed 1,4-addition of Grignard reagents to cyclohexenone using Taddol-derived phosphine-phosphite ligands and 2-methyl-THF as a solvent, T. Robert, J. Velder, H. G. Schmalz, Angew. Chem.-Int. Edit. 2008, 47, 7718-7721. DOI: https://www.doi.org/10.1002/anie.200803247

[165] Butyllithium-mediated coupling of aryl bromides with ketones under in-situ-quench (ISQ) conditions:: An efficient one-step protocol applicable to microreactor technology, S. Goto, J. Velder, S. El Sheikh, Y. Sakamoto, M. Mitani, S. Elmas, A. Adler, A. Becker, J. M. Neudörfl, J. Lex, H. G. Schmalz, Synlett 2008, 1361-1365. DOI: https://www.doi.org/10.1055/s-2008-1072771

[166] Microwave-assisted cleavage of aryl methyl ethers with lithium thioethoxide (LiSEt), J. Cvengros, S. Neufeind, A. Becker, H. G. Schmalz, Synlett 2008, 1993-1998. DOI: https://www.doi.org/10.1055/s-2008-1077949

[167] Enantioselective Synthesis of a trans-7,8-Dimethoxycalamenene, S. Werle, T. Fey, J. M. Neudorfl, H. G. Schmalz, Org. Lett. 2007, 9, 3555-3558. DOI: https://www.doi.org/10.1021/ol071228v

[168] Synthesis of a mumbaistatin analogue through cross-coupling, D. Sucunza, D. Dembkowski, S. Neufeind, J. Velder, J. Lex, H. G. Schmalz, Synlett 2007, 2569-2573. DOI: https://www.doi.org/10.1055/s-2007-986652

[169] Synthesis of 4-benzyliden-2-oxazolidinone derivatives via gold-catalyzed intramolecular hydroamination, S. Ritter, K. Hackelöer, H. G. Schmalz, Heterocycles 2007, 74, 731-742.

[170] Stereospecific side chain activation in Cyclobutadiene-Fe(CO)3 chemistry:: A theoretical and experimental study on the structure and configurational stability of cationic, radical and anionic intermediates, A. Pfletschinger, U. Schneider, J. Lex, H. G. Schmalz, Eur. J. Org. Chem. 2007, 2007, 3991-3998. DOI: https://www.doi.org/10.1002/ejoc.200700342

[171] Stereoselective syntheses of the 2-isopropenyl-2,3-dihydrobenzofuran nucleus: Potential chiral building blocks for the syntheses of tremetone, hydroxytremetone, and rotenone, S. C. Pelly, S. Govender, M. A. Fernandes, H. G. Schmalz, C. B. de Koning, J. Org. Chem. 2007, 72, 2857-2864. DOI: https://www.doi.org/10.1021/jo062447h

[172] Synthesis of the core structure of the cyclocitrinols via SmI2-mediated fragmentation of a cyclopropane precursor, S. El Sheikh, A. M. Z. Greffen, J. Lex, J. M. Neudörfl, H. G. Schmalz, Synlett 2007, 1881-1884. DOI: https://www.doi.org/10.1055/s-2007-984521

[173] Gold(I)-catalyzed reaction of 1-(1-alkynyl)-cyclopropyl ketones with nucleophiles: A modular entry to highly substituted furans, J. L. Zhang, H. G. Schmalz, Angew. Chem.-Int. Edit. 2006, 45, 6704-6707. DOI: https://www.doi.org/10.1002/anie.200601252

[174] A simple access to biologically important trans-stilbenes via Ru-catalyzed cross metathesis, J. Velder, S. Ritter, J. Lex, H. G. Schmalz, Synthesis 2006, 273-278. DOI: https://www.doi.org/10.1055/s-2005-918506

[175] Gram-scale synthesis of pinusolide and evaluation of its antileukemic potential, E. E. Shults, J. Velder, H. G. Schmalz, S. V. Chernov, T. V. Rubalova, Y. V. Gatilov, G. Henze, G. A. Tolstikov, A. Prokop, Bioorg. Med. Chem. Lett. 2006, 16, 4228-4232. DOI: https://www.doi.org/10.1016/j.bmcl.2006.05.077

[176] Gold-catalyzed cyclization of O-propargyl carbamates under mild conditions:: A convenient access to 4-alkylidene-2-oxazolidinones, S. Ritter, Y. Horino, J. Lex, H. G. Schmalz, Synlett 2006, 3309-3313. DOI: https://www.doi.org/10.1055/s-2006-951555

[177] Ferrocenyl nucleoside analogs, a new class of cytostatic drugs, overcome multiple drug resistance in acute lymphoplastic leukemia ex vivo, A. Prokop, M. Eissmann, P. Jesse, G. Henze, P. James, J. Neudoerfl, H. G. Schmalz, H. Lode, Blood 2006, 108, 179B-179B. DOI: https://www.doi.org/10.1182/blood.V108.11.4404.4404

[178] New pinostilbene analogues overcome anthracycline resistance in acute lymphoplastic leukemia ex vivo, B. Katik, A. Selig, J. Velder, E. E. Shults, T. Wieder, G. Henze, H. G. Schmalz, A. Prokop, H. Lode, Blood 2006, 108, 178B-179B. DOI: https://www.doi.org/10.1182/blood.V108.11.4403.4403

[179] Enantioselective synthesis of ferrocenyl nucleoside analogues with apoptosis-inducing activity, P. James, J. Neudörfl, M. Eissmann, P. Jesse, A. Prokop, H. G. Schmalz, Org. Lett. 2006, 8, 2763-2766. DOI: https://www.doi.org/10.1021/ol060868f

[180] Enantioselective synthesis of bicyclo 4.4.1 undecane-2,7-dione via samarium(II)-mediated fragmentation of a cyclopropane precursor, S. El Sheikh, N. Kausch, J. Lex, J. M. Neudörfl, H. G. Schmalz, Synlett 2006, 1527-1530. DOI: https://www.doi.org/10.1055/s-2006-941599

[181] Microwave-assisted amination of a chloropurine derivative in the synthesis of acyclic nucleoside analogues, A. Lanver, H. G. Schmalz, Molecules 2005, 10, 508-515. DOI: https://www.doi.org/10.3390/10020508

[182] A Pauson-Khand approach to new carbocyclic nucleoside analogs, A. Lanver, H. G. Schmalz, Eur. J. Org. Chem. 2005, 2005, 1444-1458. DOI: https://www.doi.org/10.1002/ejoc.200400886

[183] Enantioselective organocatalysis in ionic liquids: Addition of aliphatic aldehydes and ketones to diethyl azodicarboxylate, P. Kotrusz, S. Alemayehu, T. Toma, H. G. Schmalz, A. Adler, Eur. J. Org. Chem. 2005, 2005, 4904-4911. DOI: https://www.doi.org/10.1002/ejoc.200500481

[184] Total synthesis of (-)-colchicine via a Rh-triggered cycloaddition cascade, T. Graening, V. Bette, J. Neudörfl, J. Lex, H. G. Schmalz, Org. Lett. 2005, 7, 4317-4320. DOI: https://www.doi.org/10.1021/ol051316k

[185] Transition-metal-mediated synthesis of novel carbocyclic nucleoside analogues with antitumoral activity, J. Velcicky, A. Lanver, J. Lex, A. Prokop, T. Wieder, H. G. Schmalz, Chem.-Eur. J. 2004, 10, 5087-5110. DOI: https://www.doi.org/10.1002/chem.200400079

[186] Iron-containing nucleoside analogues with pronounced apoptosis-inducing activity, D. Schlawe, A. Majdalani, J. Velcicky, E. Hessler, T. Wieder, A. Prokop, H. G. Schmalz, Angew. Chem.-Int. Edit. 2004, 43, 1731-1734. DOI: https://www.doi.org/10.1002/anie.200353132

[187] Iron containing nucleosides as new cytostatic substances for cancer and leukemia therapy, especially for therapy of relapsed ALL in childhood, A. Prokop, T. Wieder, D. Schlawe, H. Lode, G. Henze, P. T. Daniel, H. G. Schmalz, Blood 2004, 104, 574A-574A. DOI: https://www.doi.org/10.1182/blood.V104.11.2085.2085

[188] Application of chromium-arene complexes in the organic synthesis. Efficient synthesis of stilbene phytoalexins, K. E. Polunin, H. G. Schmalz, Russ. J. Coord. Chem. 2004, 30, 252-261. DOI: https://www.doi.org/10.1023/B:RUCO.0000022800.70211.7d

[189] Michael additions of aldehydes and ketones to β-nitrostyrenes in an ionic liquid, P. Kotrusz, S. Toma, H. G. Schmalz, A. Adler, Eur. J. Org. Chem. 2004, 2004, 1577-1583. DOI: https://www.doi.org/10.1002/ejoc.200300648

[190] Total syntheses of colchicine in comparison: A journey through 50 years of synthetic organic chemistry, T. Graening, H. G. Schmalz, Angew. Chem.-Int. Edit. 2004, 43, 3230-3256. DOI: https://www.doi.org/10.1002/anie.200300615

[191] Halogen-lithium exchange reactions under in situ-quench conditions:: A powerful concept for organic synthesis, S. El Sheikh, H. G. Schmalz, Curr. Opin. Drug Discov. Dev. 2004, 7, 882-895.

[192] Pd-catalyzed cross-coupling of haloarenes and chloroarene-Cr(CO)3 complexes with stabilized vinyl- and allylaluminium reagents, H. Schumann, J. Kaufmann, H. G. Schmalz, A. Böttcher, B. Gotov, Synlett 2003, 1783-1788. DOI: https://www.doi.org/10.1055/s-2003-41492

[193] An enantioselective approach to cytotoxic norcalamenenes via electron-transfer-driven benzylic umpolung of an arene tricarbonyl chromium complex, H. G. Schmalz, O. Kiehl, U. Korell, J. Lex, Synthesis 2003, 1851-1855. DOI: https://www.doi.org/10.1055/s-2003-41030

[194] Studies towards the total synthesis of mumbaistatin: synthesis of highly substituted benzophenone and anthraquinone building blocks, F. Kaiser, L. Schwink, J. Velder, H. G. Schmalz, Tetrahedron 2003, 59, 3201-3217. DOI: https://www.doi.org/10.1016/s0040-4020(03)00427-7

[195] Synthetic analogues of the antibiotic pestalone, F. Kaiser, H. G. Schmalz, Tetrahedron 2003, 59, 7345-7355. DOI: https://www.doi.org/10.1016/s0040-4020(03)01136-0

[196] Pd-catalyzed enantioselective allylic substitution: New strategic options for the total synthesis of natural products, T. Graening, H. G. Schmalz, Angew. Chem.-Int. Edit. 2003, 42, 2580-2584. DOI: https://www.doi.org/10.1002/anie.200301644

[197] Catalytic-enantioselective methoxycarbonylation of 1,3-dichloroarene-tricarbonyl-chromium(0) complexes:: A desymmetrization approach to planar chirality, A. Böttcher, H. G. Schmalz, Synlett 2003, 1595-1598. DOI: https://www.doi.org/10.1055/s-2003-41417

[198] Benzylic endo-alkylation of phthalan-Cr(CO)(3) complexes via temporary silylation: An entry to trans-1,3-disubstituted dihydroisobenzofurans, S. Zemolka, J. Lex, H. G. Schmalz, Angew. Chem.-Int. Edit. 2002, 41, 2525-+. DOI: https://www.doi.org/10.1002/1521-3773(20020715)41:14<2525::Aid-anie2525>3.0.Co;2-o

[199] An efficient organometallic approach to new carbocyclic nucleoside analogues, J. Velcicky, J. Lex, H. G. Schmalz, Org. Lett. 2002, 4, 565-568. DOI: https://www.doi.org/10.1021/ol017181+

[200] Gram-scale synthesis of suspension-polymerized styrene-divinylbenzene-based resins using an oscillatory baffled reactor, D. C. Sherrington, A. Lanver, H. G. Schmalz, B. Wilson, X. W. Ni, S. G. Yuan, Angew. Chem.-Int. Edit. 2002, 41, 3656-3659. DOI: https://www.doi.org/10.1002/1521-3773(20021004)41:19<3656::Aid-anie3656>3.0.Co;2-7

[201] Synthesis and biological evaluation of new antimalarial isonitriles related to marine diterpenoids, O. Schwarz, R. Brun, J. W. Bats, H. G. Schmalz, Tetrahedron Lett. 2002, 43, 1009-1013. DOI: https://www.doi.org/10.1016/s0040-4039(01)02325-5

[202] Diallylaluminium-N,N-dimethylaminoethanolate, the first stable allyl-alane suitable for additions to aldehydes, ketones and imines, H. Schumann, J. Kaufmann, S. Dechert, H. G. Schmalz, Tetrahedron Lett. 2002, 43, 3507-3511. DOI: https://www.doi.org/10.1016/s0040-4039(02)00571-3

[203] Electron transfer driven transformations of transition metal π-complexes:: Samarium(II) iodide mediated coupling of fluoroarene-Cr(CO)3 complexes with ketones, H. G. Schmalz, O. Kiehl, B. Gotov, Synlett 2002, 1253-1256. DOI: https://www.doi.org/10.1055/s-2002-32969

[204] Chromium arene complexes in synthesis of trans-resveratrol, K. E. Polunin, H. G. Schmalz, L. A. Polunina, Russ. Chem. Bull. 2002, 51, 1319-1324. DOI: https://www.doi.org/10.1023/a:1020921101384

[205] η(6)-Arene-tricarbonylchromium complexes in the syntheses of trans-resveratrol and pinostilbene, K. E. Polunin, I. A. Polunina, H. G. Schmalz, Mendeleev Commun. 2002, 178-180. DOI: https://www.doi.org/10.1070/MC2002v012n05ABEH001616

[206] Studies toward the total synthesis of mumbaistatin, a highly potent glucose-6-phosphate translocase inhibitor. Synthesis of a mumbaistatin analogue, F. Kaiser, L. Schwink, J. Velder, H. G. Schmalz, J. Org. Chem. 2002, 67, 9248-9256. DOI: https://www.doi.org/10.1021/jo026232t

[207] Facile construction of the colchicine skeleton by a rhodium-catalyzed cyclization cycloaddition cascade, T. Graening, W. Friedrichsen, J. Lex, H. G. Schmalz, Angew. Chem.-Int. Edit. 2002, 41, 1524-1526. DOI: https://www.doi.org/10.1002/1521-3773(20020503)41:9<1524::Aid-anie1524>3.0.Co;2-9

[208] Pd-catalyzed cross-coupling of chloroarene-Cr(CO)3 complexes with stabilized organoindium (III) reagents under remarkably mild conditions, B. Gotov, J. Kaufmann, H. Schumann, H. G. Schmalz, Synlett 2002, 361-363.

[209] Pd-catalyzed carbonylative cross-coupling reactions of chloroarene-Cr(CO)3 complexes, B. Gotov, J. Kaufmann, H. Schumann, H. G. Schmalz, Synlett 2002, 1161-1163.

[210] An approach to serrulatane diterpenes via endo-selective conjugate nucleophilic addition to arene-Cr(CO)3 complexes, F. Dehmel, J. Lex, H. G. Schmalz, Org. Lett. 2002, 4, 3915-3918. DOI: https://www.doi.org/10.1021/ol026827a

[211] Identification of suitable ligands for a transition metal-catalyzed reaction: Screening of a modular ligand library in the enantioselective hydroboration of styrene, F. Blume, S. Zemolka, T. Fey, R. Kranich, H. G. Schmalz, Adv. Synth. Catal. 2002, 344, 868-883. DOI: https://www.doi.org/10.1002/1615-4169(200209)344:8<868::Aid-adsc868>3.0.Co;2-m

[212] Piceatannol, a hydroxylated analog of the chemopreventive agent resveratrol, is a potent inducer of apoptosis in the lymphoma cell line BJAB and in primary, leukemic lymphoblasts, T. Wieder, A. Prokop, B. Bagci, F. Essmann, D. Bernicke, K. Schulze-Osthoff, B. Dörken, H. G. Schmalz, P. T. Daniel, G. Henze, Leukemia 2001, 15, 1735-1742. DOI: https://www.doi.org/10.1038/sj.leu.2402284

[213] (CH2=CH)(2)Al(mu-OCH2CH2NMe2) (2): a vinylalane reagent suitable for conjugate additions to alpha,beta-unsaturated ketones, H. Schumann, J. Kaufmann, S. Dechert, H. G. Schmalz, J. Velder, Tetrahedron Lett. 2001, 42, 5405-5408. DOI: https://www.doi.org/10.1016/s0040-4039(01)01026-7

[214] Piceatannol, a hydroxylated analog of the chemopreventive agent resveratrol, is a potent inducer of apoptosis in the lymphoma cell line BJAB and in primary, leukemic lymphoblasts, A. Prokop, T. Wieder, B. Bagci, F. Essmann, D. Bernicke, K. Schulze-Osthoff, B. Dörken, H. G. Schmalz, G. Henze, P. T. Daniel, Blood 2001, 98, 220B-220B.

[215] On the regioselectivity of nucleophilic additions to anisole-Cr(CO)3 and related complexes:: a density functional study, A. Pfletschinger, W. Koch, H. G. Schmalz, New J. Chem. 2001, 25, 446-450. DOI: https://www.doi.org/10.1039/b002898n

[216] Density functional investigation of reactive intermediates derived from alkyne-CO2(CO)6 complexes, A. Pfletschinger, W. Koch, H. G. Schmalz, Chem.-Eur. J. 2001, 7, 5325-5332. DOI: https://www.doi.org/10.1002/1521-3765(20011217)7:24<5325::Aid-chem5325>3.0.Co;2-s

[217] On the antioxidative activity of several dihydropyridine derivatives, W. Gutwirth, M. Beer, T. Naumann, B. Lauven, K. Güttler, H. G. Schmalz, W. Klaus, Naunyn-Schmiedebergs Arch. Pharmacol. 2001, 363, R70-R70.

[218] A catalytic-enantioselective entry to planar chiral π-complexes: Enantioselective methoxycarbonylation of 1,2-dichlorobenzene-Cr(CO)3, B. Gotov, H. G. Schmalz, Org. Lett. 2001, 3, 1753-1756. DOI: https://www.doi.org/10.1021/ol0159468

[219] Unexpected endo selectivity of conjugate nucleophilic addition to an arene-Cr(CO)3 complex:: Enantioselective synthesis of the diterpene 11-epi-helioporin B, F. Dehmel, H. G. Schmalz, Org. Lett. 2001, 3, 3579-3582. DOI: https://www.doi.org/10.1021/ol016699a

[220] A modular approach to structurally diverse bidentate chelate ligands for transition metal catalysis, R. Kranich, K. Eis, O. Geis, S. Mühle, J. W. Bats, H. G. Schmalz, Chem.-Eur. J. 2000, 6, 2874-2894. DOI: https://www.doi.org/10.1002/1521-3765(20000804)6:15<2874::Aid-chem2874>3.0.Co;2-1

[221] Kinetic investigation of the reduction of pinacolone by borane catalyzed by oxazaborolidines in THF. Hydride shift as rate determining step, H. Jockel, R. Schmidt, H. Jope, H. G. Schmalz, J. Chem. Soc.-Perkin Trans. 2 2000, 69-76. DOI: https://www.doi.org/10.1039/a906935f

[222] Memory of chirality in electron transfer mediated benzylic umpolung reactions of arene-Cr(CO)3 complexes, H. G. Schmalz, C. B. de Koning, D. Bernicke, S. Siegel, A. Pfletschinger, Angew. Chem.-Int. Edit. 1999, 38, 1620-1623. DOI: https://www.doi.org/10.1002/(sici)1521-3773(19990601)38:11<1620::Aid-anie1620>3.0.Co;2-1

[223] Structural and energetical characterization of the methylbutadiene-Fe(CO)3 isomers and related reactive intermediates with quantum chemical methods, A. Pfletschinger, H. G. Schmalz, W. Koch, Eur. J. Inorg. Chem. 1999, 1869-1880.

[224] Structural and energetical characterization of reactive intermediates derived from toluene-Cr(CO)3, A. Pfletschinger, T. K. Dargel, J. W. Bats, H. G. Schmalz, W. Koch, Chem.-Eur. J. 1999, 5, 537-545. DOI: https://www.doi.org/10.1002/(sici)1521-3765(19990201)5:2<537::Aid-chem537>3.0.Co;2-i

[225] Synthesis of an analog of the cytotoxic marine diterpene helioporin C exploiting arene-Cr(CO)3 chemistry, D. Hörstermann, H. G. Schmalz, G. Kociok-Köhn, Tetrahedron 1999, 55, 6905-6916. DOI: https://www.doi.org/10.1016/s0040-4020(99)00346-4

[226] 2-aminobenzimidazolium nitrate at 152 K, a triclinic crystal structure with pronounced local pseudo-symmetry, J. W. Bats, D. Gördes, H. G. Schmalz, Acta Crystallogr. Sect. C-Cryst. Struct. Commun. 1999, 55, 1325-1328. DOI: https://www.doi.org/10.1107/s0108270199004710

[227] Highly regioselective benzylic deprotonation of some (η6-tetralin)- and (η6-trans-octahydroanthracene)Cr(CO)3 derivatives:: Is the regioselectivity stereoelectronically controlled?", T. Volk, D. Bernicke, J. W. Bats, H. G. Schmalz, Eur. J. Inorg. Chem. 1998, 1883-1905.

[228] Electron transfer driven reactions of transition metal π-complexes:: Hydrogenation of styrene-Cr(CO)3 derivatives by samarium(II)iodide in the presence of water, H. G. Schmalz, S. Siegel, D. Bernicke, Tetrahedron Lett. 1998, 39, 6683-6686. DOI: https://www.doi.org/10.1016/s0040-4039(98)01436-1

[229] On the oxazaborolidine-catalyzed borane reduction of 1-tetralone-Cr(CO)3 complexes:: The control of the reagent over a strong substrate, H. G. Schmalz, H. Jope, Tetrahedron 1998, 54, 3457-3464. DOI: https://www.doi.org/10.1016/s0040-4020(98)00078-7

[230] Chiral η6-arene-Cr(CO)(3) complexes as synthetic building blocks: A short enantioselective total synthesis of (+)-ptilocaulin, K. Schellhaas, H. G. Schmalz, J. W. Bats, Chem.-Eur. J. 1998, 4, 57-66. DOI: https://www.doi.org/10.1002/(sici)1521-3765(199801)4:1<57::Aid-chem57>3.0.Co;2-h

[231] Electron transfer driven addition of ketimine derived radicals to arene-Cr(CO)3 complexes, O. Hoffmann, H. G. Schmalz, Synlett 1998, 1426-1428.

[232] Chiral arene-Cr(CO)3 complexes in organic synthesis: A short enantioselective total synthesis of putative helioporin D, T. Geller, H. G. Schmalz, J. W. Bats, Tetrahedron Lett. 1998, 39, 1537-1540. DOI: https://www.doi.org/10.1016/s0040-4039(98)00021-5

[233] Preparation of helioporin D from the seco-pseudopterosin aglycone: Revision of the stereostructure of helioporin D, T. Geller, J. Jakupovic, H. G. Schmalz, Tetrahedron Lett. 1998, 39, 1541-1544. DOI: https://www.doi.org/10.1016/s0040-4039(98)00020-3

[234] New developments in the Pauson-Khand reaction, O. Geis, H. G. Schmalz, Angew. Chem.-Int. Edit. 1998, 37, 911-914. DOI: https://www.doi.org/10.1002/(sici)1521-3773(19980420)37:7<911::Aid-anie911>3.0.Co;2-o

[235] Enantioselective synthesis of new C-2-symmetric ferrocenylalkylamines via sonochemical amination of 1-ferrocenylalkyl acetates, M. Woltersdorf, R. Kranich, H. G. Schmalz, Tetrahedron 1997, 53, 7219-7230. DOI: https://www.doi.org/10.1016/s0040-4020(97)00407-9

[236] Insertion of carbenoids into Cp-H bonds of ferrocenes: An enantioselective-catalytic entry to planar-chiral ferrocenes, S. Siegel, H. G. Schmalz, Angew. Chem.-Int. Edit. Engl. 1997, 36, 2456-2458. DOI: https://www.doi.org/10.1002/anie.199724561

[237] Kinetics of the borane reduction of pinacolone in THF catalyzed by two different oxazaboroles, R. Schmidt, H. Jockel, H. G. Schmalz, H. Jope, J. Chem. Soc.-Perkin Trans. 2 1997, 2725-2731. DOI: https://www.doi.org/10.1039/a703700g

[238] On the deprotonation of η(6)-1,3-dimethoxybenzene-Cr(CO)(3) derivatives: Influence of the reaction conditions on the regioselectivity, H. G. Schmalz, T. Volk, D. Bernicke, S. Huneck, Tetrahedron 1997, 53, 9219-9232. DOI: https://www.doi.org/10.1016/s0040-4020(97)00620-0

[239] Chiral η(6)-arene-Cr(CO)(3) complexes in organic synthesis: A short and highly selective synthesis of the 18-nor-seco-pseudopterosin aglycone, A. Majdalani, H. G. Schmalz, Tetrahedron Lett. 1997, 38, 4545-4548. DOI: https://www.doi.org/10.1016/s0040-4039(97)00995-7

[240] Enantioselective synthesis of the aglycones of pseudopterosin and seco-pseudopterosin via a common synthetic intermediate, A. Majdalani, H. G. Schmalz, Synlett 1997, 1303-&.

[241] Synthesis of (E,E,E)-(1,2,3,4-C-13(4))-geranylgeraniol, K. Eis, H. G. Schmalz, Synthesis 1997, 202-+.

[242] Asymmetric induction in the nucleophile addition to eta(6)-arene-tricarbonyl-chromium(0) complexes, M. F. Semmelhack, H. G. Schmalz, Tetrahedron Lett. 1996, 37, 3089-3092. DOI: https://www.doi.org/10.1016/0040-4039(96)00572-2

[243] Radical cyclization of η(6)-arene-Cr(CO)(3) complexes: A regio- and stereoselective entry to functionalized pseudopterosin precursors, H. G. Schmalz, S. Siegel, A. Schwarz, Tetrahedron Lett. 1996, 37, 2947-2950. DOI: https://www.doi.org/10.1016/0040-4039(96)00486-8

[244] Controlling the course of nucleophilic additions to ortho-substituted (η(6)-anisole)tricarbonyl-chromium complexes: Dienol ether formation versus tele-substitution, H. G. Schmalz, K. Schellhaas, Angew. Chem.-Int. Edit. Engl. 1996, 35, 2146-2148. DOI: https://www.doi.org/10.1002/anie.199621461

[245] Radical Additions to (η6‐Arene)(tricarbonyl)‐chromium Complexes: Diastereoselective Synthesis of Hydrophenalene and Hydrobenzindene Derivatives by Samarium(II) Iodide Induced Cyclization, H. G. Schmalz, S. Siegel, J. W. Bats, Angew. Chem.-Int. Edit. Engl. 1995, 34, 2383-2385. DOI: https://www.doi.org/10.1002/anie.199523831

[246] On the enantioselective deprotonation/silylation of prochiral mono- and 1,2-dimethoxybenzene-Cr(CO)3 derivatives, H. G. Schmalz, K. Schellhaas, Tetrahedron Lett. 1995, 36, 5515-5518.

[247] tele-Substitution as the major pathway in intermolecular nucleophilic addition/protonation reactions of ortho-alkylated η6-anisole-Cr(CO)3 derivatives, H. G. Schmalz, K. Schellhaas, Tetrahedron Lett. 1995, 36, 5511-5514.

[248] Diastereoselective transformation of chiral η6-Arene-Cr(CO)3 complexes: Enantioselective synthesis of functionalized hydronaphthalene derivatives related to the seco-pseudopterosins, H. G. Schmalz, A. Majdalani, T. Geller, J. Hollander, J. W. Bats, Tetrahedron Lett. 1995, 36, 4777-4780.

[249] Catalytic Ring‐Closing Metathesis: A New, Powerful Technique for Carbon–Carbon Coupling in Organic Synthesis, H. G. Schmalz, Angew. Chem.-Int. Edit. Engl. 1995, 34, 1833-1836. DOI: https://www.doi.org/10.1002/anie.199518331

[250] Chemistry in Germany -: off the defensive, C. Bolm, B. Frauendorf, A. Griesbeck, U. Kliem, A. Kretschmer, H. C. Militzer, G. Müller, H. Perry, H. J. Rosenkranz, H. G. Schmalz, W. Schnick, A. D. Schlüter, R. Stadler, S. Waffenschmidt, Nachr. Chem. Tech. Lab. 1995, 43, 942-+.

[251] Chiral η6-arene-Cr(CO)3 complexes as synthetic building blocks: An enantio- and diastereoselective approach to substituted hydrophenalenes related to helioporin E and pseudopterosin G, H. G. Schmalz, A. Schwarz, G. Durner, Tetrahedron Lett. 1994, 35, 6861-6864. DOI: https://www.doi.org/10.1016/0040-4039(94)85024-0

[252] An approach to chiral η4-butadiene-Fe(CO)3 complexes via diastereoselective complexation of nonracemic 2-alkoxy-4-vinyl-2,5-dihydrofuran derivatives, H. G. Schmalz, E. Hessler, J. W. Bats, G. Durner, Tetrahedron Lett. 1994, 35, 4543-4546. DOI: https://www.doi.org/10.1016/s0040-4039(00)60723-2

[253] The Total Synthesis of cis‐7,8‐Dihydroxy‐11,12‐dehydrocalamenene by Regio‐ and Diastereo‐selective Alkylation of Chiral η6‐Arenetricarbonylchromium Complexes: An Unexpected Case of Nucleophilic Aromatic tele‐Substitution with Methoxide as a Leaving Group, H. G. Schmalz, M. Arnold, J. Hollander, J. W. Bats, Angew. Chem. Int. Ed., 199, H. G. Schmalz, M. Arnold, J. Hollander, J. W. Bats, Angew. Chem.-Int. Edit. Engl. 1994, 33, 109-111. DOI: https://www.doi.org/10.1002/anie.199401091

[254] Chromium Carbene Complexes in Organic Synthesis: Recent Developments and Perspectives, H. G. Schmalz, Angew. Chem.-Int. Edit. Engl. 1994, 33, 303-305. DOI: https://www.doi.org/10.1002/anie.199403031

[255] Enantioselektive Heck‐Reaktionen, H. G. Schmalz, Nachr. Chem. Tech. Lab. 1994, 42, 270-&.

[256] Pd‐katalysierte Synthesen Vitamin‐D‐aktiver Verbindungen, H. G. Schmalz, Nachr. Chem. Tech. Lab. 1994, 42, 394-+.

[257] Zr‐katalysierte Carbomagnesierungen von Alkenen, H. G. Schmalz, Nachr. Chem. Tech. Lab. 1994, 42, 724-729.

[258] Eisenvermittelte Totalsynthese von Ikarugamycin, H. G. Schmalz, Nachr. Chem. Tech. Lab. 1994, 42, 1016-&.

[259] Intramolekulare Alkoxypalladierungen, H. G. Schmalz, Nachr. Chem. Tech. Lab. 1994, 42, 1267-&.

[260] Chiral η4-butadiene-Fe(CO)3 complexes for organic synthesis: Reactions of (η4-2-alkoxy-4-vinyl-2,5-dihydrofuran)-Fe(CO)3 derivatives, E. Hessler, H. G. Schmalz, G. Durner, Tetrahedron Lett. 1994, 35, 4547-4550. DOI: https://www.doi.org/10.1016/s0040-4039(00)60724-4

[261] Total synthesis of (1S,4S)-7,8-dihydroxycalamenene via benzylic alkylation of η6-arene-Cr(CO)3 complexes, H. G. Schmalz, J. Hollander, M. Arnold, G. Durner, Tetrahedron Lett. 1993, 34, 6259-6262. DOI: https://www.doi.org/10.1016/s0040-4039(00)73725-7

[262] Diastereoselective Complexation of Temporarily Chirally Modified Ligands: Enantioselective Preparation and Configurational Assignment of Synthetically Valuable η6‐Tricarbonylchromium‐1‐tetralone Derivatives, H. G. Schmalz, B. Millies, J. W. Bats, G. Durner, Angew. Chem.-Int. Edit. Engl. 1992, 31, 631-633. DOI: https://www.doi.org/10.1002/anie.199206311

[263] Totalsynthese des Pseudoguaianolids (+)‐Confertin, G. Quinkert, H. G. Schmalz, E. Walzer, S. Gross, T. Kowalczykprzewloka, C. Schierloh, G. Durner, J. W. Bats, H. Kessler, Liebigs Annalen Der Chemie 1988, 283-315.

[264] Total Synthesis of the Pseudoguaianolide (+)‐Confertin, G. Quinkert, H. G. Schmalz, Egonwalzer, T. Kowalczykprzewloka, G. Durner, J. W. Bats, Angew. Chem.-Int. Edit. 1987, 26, 61-62. DOI: https://www.doi.org/10.1002/anie.198700611

[265] The Use of (+)‐8‐Phenylneomenthol in the Synthesis of Enantiomerically Pure (−)‐Jasmonate Methyl Ester, G. Quinkert, H. G. Schmalz, E. M. Dzierzynski, G. Durner, J. W. Bats, Angew. Chem.-Int. Edit. Engl. 1986, 25, 992-993. DOI: https://www.doi.org/10.1002/anie.198609921

[266] (R)‐2‐Isopropenylcyclopropane‐1,1‐dicarboxylic Acid: Absolute Configuration and Stereospecific Ring Expansion of Its Dimethyl Ester, G. Quinkert, H. G. Schmalz, Angew. Chem.-Int. Edit. Engl. 1986, 25, 732-734. DOI: https://www.doi.org/10.1002/anie.198607321