Recently Published

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

L. Hemmersbach, Y. Schreiner, X. Zhang, F. Dicke, L. Hünemeyer, J.-M. Neudörfl, T. Fleming, B. Yard, H.-G. Schmalz Chem. Eur. J. 2022, early view, e202201670, 10.1002/chem.202201670

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 μM (MTT assay), Mito-CORMs 2/3-A’ caused significant toxicity at concentrations above 50 μM. 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 TNFα-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.

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, Advance Article, 10.1039/D2MD00144F

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%.

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, e202200372, 10.1002/cbic.202200372

During viral cell entry, the spike protein of SARS-CoV-2 binds to the α1-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 α-helicity in short peptide sequences inspired by the ACE2 α1-helix. Starting with Ac-QAKTFLDKFNHEAEDLFYQ-NH₂ as a relevant section of α1, a series of peptides, N-capped with either Ac-βHAsp-[ProM-5] or Ac-βHAsp-PP, were prepared and their α-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 α-helical content and, noteworthy, led to the identification of an Ac-βHAsp-PP-capped peptide displaying a very strong binding affinity (K_D=62 nM).

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, (12), e202200188, 10.1002/ejoc.202200188

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 (≥95 % 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 outstanding levels of diastereocontrol (d.r. ≥99 : 1) and negligible matched/mismatched differences.

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

Christian E. Schumacher, M. Rausch, T. Greven, J.-M. Neudörfl, T. Schneider, H.-G. Schmalz, Eur. J. Org. Chem. 2022, e202200058, 10.1002/ejoc.202200058

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 μg/ml), but also against Gram-negative bacterial strains (E. coli K12; E. coli I-11276b; MIC=8 to 32 μg/ml). This clearly supported the underlying working hypothesis.

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. Hilken née 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(3), 2591, 10.1021/acsomega.1c04659

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 β-tubulin at the interface to the α-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.

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(12), 2747, 10.1021/acs.oprd.1c00364

We report a greatly improved, operationally simple, and scalable three-step synthesis of the nonionic and water-soluble singlet oxygen (¹O₂) carrier molecule N,N′-bis(2,3-dihydroxypropyl)-1,4-naphthalenedipropanamide-1,4-endoperoxide (DHPNO₂). Starting from 1,4-dibromonaphthalene, the developed sequence involves (1) a ligand-free Pd-catalyzed double Heck reaction with methyl acrylate, (2) Pd/C-catalyzed hydrogenation, and (3) amide formation by simple methyl ester aminolysis using 3-amino-1,2-propanediol to give N,N′-bis(2,3-dihydroxypropyl)-1,4-naphthalenedipropanamide (DHPN) in 70% overall yield (three steps). A solution of the corresponding endoperoxide DHPNO₂ in D₂O (storable at −20 °C), obtained by sensitized photo-oxidation of DHPN at 4 °C, is a valuable research tool allowing a controlled release of singlet oxygen (¹O₂) in aqueous biological systems at physiological temperatures.

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, 10.1039/D1MD00163A

Endogenous itaconate as well as the gasotransmitter CO have recently been described as powerful anti-inflammatory and immunomodulating agents. However, each of the two agents comes along with a major drawback: Whereas itaconates only exert beneficial effects at high concentrations above 100 μM, the uncontrolled application of CO has strong toxic effects. To solve these problems, we designed hybrid prodrugs, i.e. itaconates that are conjugated with an esterase-triggered CO-releasing acyloxycyclohexadiene–Fe(CO)₃ unit (ItaCORMs). Here, we describe the synthesis of different ItaCORMs and demonstrate their anti-inflammatory potency in cellular assays of primary murine immune cells in the low μmolar range (<10 μM). Thus, ItaCORMs represent a promising new class of hybrid compounds with high clinical potential as anti-inflammatory agents.

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

Y. Li, L. Hemmersbach, B. Krause, N. Sitnikov, A. Schlundt née Göderz, D. O. P. Maldonado, H.-G. Schmalz, B. Yard, ChemBioChem 2021, 23(1), e202100452, 10.1002/cbic.202100452

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-α-stimulated human umbilical vein endothelial cells (HUVEC) was evaluated.

ET-CORM Mediated Vasorelaxation of Small Mesenteric Arteries: Involvement of Kv7 Potassium Channels

D. Zhang, B. M. Krause, H.-G. Schmalz, P. Wohlfart, B. A. Yard, R. Schubert, Front. Pharmacol. 2021, 12, 702392, 10.3389/fphar.2021.702392

Although the vasoactive properties of carbon monoxide (CO) have been extensively studied, the mechanism by which CO mediates vasodilation is not completely understood. Through-out published studies on CO mediated vasodilation there is inconsistency on the type of K+ -channels that are activated by CO releasing molecules (CORMs). Since the vasorelaxation properties of enzyme triggered CORMs (ET-CORMs) have not been studied thus far, we first assessed if ET-CORMs can mediate vasodilation of small mesenteric arteries and subsequently addressed the role of soluble guanylate cyclase (sGC) and that of K-channels herein. To this end, 3 different types of ETCORMs that either contain acetate (rac-1 and rac-4) or pivalate (rac-8) as ester functionality, were tested ex vivo on methoxamine pre-contracted small rat mesenteric arteries in a myograph setting. Pre-contracted mesenteric arteries strongly dilated upon treatment with both types of acetate containing ET-CORMs (rac-1 and rac-4), while treatment with the pivalate containing ET-CORM (rac-8) resulted in no vasodilation. Pretreatment of mesenteric arteries with the sGC inhibitor ODQ abolished rac-4 mediated vasodilation, similar as for the known sGC activator SNP. Likewise, rac-4 mediated vasodilation did not occur in KCL pretreated mesenteric arteries. Although mesenteric arteries abundantly expressed a variety of K+ -channels only Kv7 channels were found to be of functional relevance for rac-4 mediated vasodilation. In conclusion the current results identified Kv7 channels as the main channel by which rac-4 mediates vasodilation. In keeping with the central role of Kv7 in the control of vascular tone and peripheral resistance these promising ex-vivo data warrant further in vivo studies, particularly in models of primary hypertension or cardiac diseases, to assess the potential use of ET-CORMs in these diseases.

Some Surprising Transformations of Colchicone and Other Colchicine-Derived Tropolones

A. Stein, P. Hilken née Thomopoulou,T. Schulte, J.-M. Neudörfl, M. Breugst, H.-G. Schmalz, Eur. J. Org. Chem. 2021, early view, 10.1002/ejoc.202100999

The alkaloid colchicine represents a prominent lead structure for the development of tubulin-binding chemotherapeutics. In the course of explorative research into semi-synthetic colchicinoids we stumbled upon a number of unexpected and mechanistically surprising transformations which reflect the very particular reactivity of the tropolone ether unit and its interplay with adjacent functional groups. Examples are the selective C-8-methylation of colchicone upon reaction with the Wittig reagent triphenylphosphonium methylide, the AlMe₃-mediated isomerization of colchicone to a tetracyclic lactone, and the cyanide-induced reaction of the colchicol-derived mesylate to a rearranged and ring B-defunctionalized cyano-allo-colchicinoid. Finally, the fragmenting rearrangement of a tetracyclic colchicinoid with BF₃^.OEt₂ in the presence of vinyl-MgBr afforded a tropolonyl difluoroborate under concomitant transfer of an O-methyl group from ring C to ring A.

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(16), 2909, 10.1021/acs.organomet.1c00354

In the course of an attempt to synthesize 2-acyloxycyclohexa-1,3-diene-Fe(CO)₃ complexes in nonracemic form, we reinvestigated the “fully diastereoselective” Fe(CO)₃ complexation of (S,S)-2-ketopinoyloxy-1,3-cyclohexadiene, which had been described by Yeh and co-workers (Organometallics 2001, 20, 289−295). However, after cleaving off the chiral auxiliary unit, we only obtained racemic complexes, also for a related substrate. For this reason, we performed control experiments to exclude possible racemization mechanisms and confirmed the configurational integrity of the dienol-Fe(CO)₃ intermediates using stereochemically defined dihydrocarvone-derived complexes. We finally could show that the complexation described by Yeh actually proceeds without any detectable diastereoselectivity. At the end, the virtually inseparable diastereomers of the chiral complexation products could be distinguished by careful NMR and chiral HPLC analyses.

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, (29), 4237, 10.1002/ejoc.202100748

Abstract

A new class of chiral C₂-symmetric diphosphines (MediPhos) was recently shown to give superior results in the Pd-catalyzed asymmetric N-allylation of amino acid esters. We here describe a new, improved protocol for the preparation of such ligands through bidirectional S_N2-coupling of a tartrate-derived ditosylate with 6-alkyl-2-bromophenols followed by double lithiation/phosphanylation. This method opened access to a series of nine ligands with branched alkyl substituents, which were benchmarked in the enantioselective Pd-catalyzed N-allylation of tert-butyl glycinate with racemic (E)-2,8-dimethylnona-5-en-4-yl methyl carbonate (up to 95% ee). In addition, the analogous transformation of tert -butyl glycinate with methyl (E)-nona-5-en-4-yl carbonate was optimized. The obtained allylic amines were then used in the stereoselective synthesis of the conformationally restricted proline-derived dipeptide analogs ProM-17 and ProM-21 .

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 (45), 11574, 10.1002/chem.202101863

Abstract

Due to their pronounced bioactivity and limited availability from natural resources, metabolites of the soft coral Pseudopterogorgia elisabethae, such as erogorgiaene and the pseudopterosines, represent important target molecules for chemical synthesis. We have now developed a particularly short and efficient route towards these marine diterpenes exploiting an operationally convenient enantioselective cobalt-catalyzed hydrovinylation as the chirogenic step. Other noteworthy C−C bond forming transformations include diastereoselective Lewis acid-mediated cyclizations, a Suzuki coupling and a carbonyl ene reaction. Starting from 4-methyl-styrene the anti-tubercular agent (+)-erogorgiaene (>98 % ee) was prepared in only 7 steps with 46 % overall yield. In addition, the synthesis of the pseudopterosin A aglycone was achieved in 12 steps with 30 % overall yield and, surprisingly, was found to exhibit a similar anti-inflammatory activity (inhibition of LPS-induced NF-κB activation) as a natural mixture of pseudopterosins A−D or iso-pseudopterosin A, prepared by β-D-xylosylation of the synthetic aglycone.

Enantioselective Total Synthesis and Structural Revision of Dysiherbol A

J. Baars, I. Grimm, D. Blunk, J.-M. Neudörfl, H.-G. Schmalz, Angew. Chem. Int. Ed. 2021, 60 (27), 14915, 10.1002/anie.202105733

Abstract

A 12-step total synthesis of the natural product dysiherbol A, a strongly anti-inflammatory and anti-tumor avarane meroterpene isolated from the marine sponge Dysidea sp., was elaborated. As key steps, the synthesis features an enantioselective Cu-catalyzed 1,4-addition/enolate-trapping opening move, an Au-catalyzed double cyclization to build up the tetracyclic core-carbon skeleton, and a late installation of the C5-bridgehead methyl group via proton-induced cyclopropane opening associated with spontaneous cyclic ether formation. The obtained pentacyclic compound (corresponding to an anhydride of the originally suggested structure for dysiherbol A) showed identical spectroscopic data as the natural product, but an opposite molecular rotation. CD-spectroscopic measurements finally confirmed that both the constitution and the absolute configuration of the originally proposed structure of (+)-dysiherbol A need to be revised.

A Concise Synthesis of 24,25-Dihydro-6-epi-Monanchosterol A

Ö. Taspinar, V. K. Stojadinovic, J.-M. Neudörfl, H.-G. Schmalz, Synlett 2021, 32 (11), 1085, 10.1055/a-1480-5225

Abstract

We report the first synthetic entry to a steroid with an unusual bicyclo[4.3.1]dec-3-en-10-one A/B ring substructure as a close structural analogue of the anti-inflammatory monanchosterols. Under optimized conditions, regioselective cis-dihydroxylation of the Δ⁵-double bond of 7-dehydrocholesterol and subsequent Criegee oxidation yields the corresponding 5,6-seco-steroid as a pure Z-isomer which upon treatment with K₂CO₃ in MeOH diastereoselectively affords 24,25-dihydro-6-epi-monanchosterol A through intramolecular aldol addition (cyclization). The developed three-step sequence proceeds in 17% overall yield without the need of any protecting group. The title compound was characterized by X-ray crystallography.

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 (11), 1089, 10.1055/a-1493-9078

Abstract

A General Stereocontrolled Synthesis of Opines via Asymmetric Pd‐Catalyzed N‐Allylation of Amino Acid Esters

D. Albat, J.-M. Neudörfl, H.-G. Schmalz, Eur. J. Org. Chem. 2021, (14), 2099, 10.1002/ejoc.202100259

Abstract

A stereo‐divergent synthesis of natural and unnatural opines in stereochemically pure form is based on the direct palladium‐catalyzed N ‐allylation of a‐amino acid esters (up to 97% e.e. or 99:1 d.r.) using methyl (E)‐2‐penten‐4‐yl carbonate in the presence of only 1 mol% of a catalyst prepared in‐situ from the C 2 ‐symmetric diphosphine i Pr‐MediPhos and [Pd(allyl)Cl] 2 . Selected target compounds (incl. a derivative of the drug enalapril) were efficiently obtained from the N ‐allylated intermediates by oxidative cleavage (ozonolysis) of the allylic C=C bond under temporary N ‐Boc‐protection.

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(14), 4640, 10.1002/chem.202004843

Abstract

The Ir‐catalyzed conversion of prochiral tert‐cyclobutanols to β‐methyl‐substituted ketones proceeds under comparably mild conditions in toluene (45–110 °C) and is particularly suited for the enantioselective desymmetrization of β‐oxy‐substituted substrates to give products with a quaternary chirality center with up to 95 % ee using DTBM‐SegPhos as a chiral ligand. Deuteration experiments and kinetic isotope effect measurements revealed major mechanistic differences to related Rh^I‐catalyzed transformations. Supported by DFT calculations we propose the initial formation of an Ir^III hydride intermediate, which then undergoes a β‐C elimination (C−C bond activation) prior to reductive C−H elimination. The computational model also allows the prediction of the stereochemical outcome. The Ir‐catalyzed cyclobutanol cleavage is broadly applicable but fails for substrates bearing strongly coordinating groups. The method is of particular value for the stereo‐controlled synthesis of substituted chromanes related to the tocopherols and other natural products.

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, PNAS 2020, 117(47), 29684, 10.1073/pnas.2007213117

Abstract

Battling metastasis through inhibition of cell motility is considered a promising approach to support cancer therapies. In this context, Ena/VASP-depending signaling pathways, in particular interactions with their EVH1 domains, are promising targets for pharmaceutical intervention. However, protein–protein interactions involving proline-rich segments are notoriously difficult to address by small molecules. Hence, structure-based design efforts in combination with the chemical synthesis of additional molecular entities are required. Building on a previously developed nonpeptidic micromolar inhibitor, we determined 22 crystal structures of ENAH EVH1 in complex with inhibitors and rationally extended our library of conformationally defined proline-derived modules (ProMs) to succeed in developing a nanomolar inhibitor (Kd=120 nM, MW=734). In contrast to the previous inhibitor, the optimized compounds reduced extravasation of invasive breast cancer cells in a zebrafish model. This study represents an example of successful, structure-guided development of low molecular weight inhibitors specifically and selectively addressing a proline-rich sequence-recognizing domain that is characterized by a shallow epitope lacking defined binding pockets. The evolved high-affinity inhibitor may now serve as a tool in validating the basic therapeutic concept, i.e., the suppression of cancer metastasis by inhibiting a crucial protein–protein interaction involved in actin filament processing and cell migration.

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(19), 10618, 10.1021/acs.jmedchem.0c00222

Abstract

Colchicine, the main alkaloid of Colchicum autumnale, is one of the most famous natural molecules. Although colchicine belongs to the oldest drugs (in use since 1500 BC), its pharmacological potential as a lead structure is not yet fully exploited. This review is devoted to the synthesis and structure–activity relationships (SAR) of colchicine alkaloids and their analogues with modified A, B, and C rings, as well as hybrid compounds derived from colchicinoids including prodrugs, conjugates, and delivery systems. The systematization of a vast amount of information presented to date will create a paradigm for future studies of colchicinoids for neoplastic and various other diseases.

Synthesis of the 8,19-Epoxysteroid Eurysterol A

Ö. Taspinar, T. Wilczek, J. Erver, M. Breugst, J.-M. Neudoerfl, H.-G. Schmalz, Chem. Eur. J. 2020, 26(19), 4256, 10.1002/chem.202000585

Abstract

We report the first chem. synthesis of eurysterol A (I), a cytotoxic and antifungal marine steroidal sulfate with a unique C8- C19 oxy-bridged cholestane skeleton. After C19 hydroxy lation of cholesteryl acetate, used as an inexpensive com. starting material, the challenging oxidative functionalization of ring B was achieved by two different routes to set up a 5α- hydroxy-7-en-6-one moiety. As a key step, an intramol. oxa-Michael addition was exploited to close the oxy-bridge (8β,19-epoxy unit). DFT calculations show this reversible transformation being exergonic by about - 30 kJ mol . Along the optimized (scalable) synthetic sequence, the target natural product was obtained in only 11 steps in 5 % overall yield. In addition, an access to (isomeric) 7β,19-epoxy steroids with a previously unknown pentacyclic ring system was discovered.

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. Neudoerfl, R. Kuehne, H.-G. Schmalz, Chem. Eur. J. 2020, 26(14), 3049, 10.1002/chem.202000307

Abstract

A general and powerful method for the stereo‐controlled Pd‐catalyzed N‐allylation of amino acid esters is reported, as a previously largely unsolved synthetic challenge. Employing a new class of tartaric acid‐derived C₂‐symmetric chiral diphosphane ligands the developed asymmetric amination protocol allows the conversion of various amino acid esters to the N‐allylated products with highest levels of enantio‐ or diastereoselectivity in a fully catalyst‐controlled fashion and predictable configuration. Remarkably, the in situ generated catalysts also exhibit outstanding levels of activity (ligand acceleration). The usefulness of the method was demonstrated in the stereo‐divergent synthesis of a set of new conformationally defined dipeptide mimetics, which represent new modular building blocks for the development of peptide‐inspired bioactive compounds.

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. Ed. 2020, 59(14), 5747, 10.1002/anie.201914101

Abstract

Collagen model peptides (CMPs) serve as tools for understanding stability and function of the collagen triple helix and have a potential for biomedical applications. In the past, interstrand cross‐linking or conformational preconditioning of proline units through stereoelectronic effects have been utilized in the design of stabilized CMPs. To further study the effects determining collagen triple helix stability we investigated a series of CMPs containing synthetic diproline‐mimicking modules (ProMs), which were preorganized in a PPII‐helix‐type conformation by a functionalizable intrastrand C₂ bridge. Results of CD‐based denaturation studies were correlated with calculated (DFT) conformational preferences of the ProM units, revealing that the relative helix stability is mainly governed by an interplay of main‐chain preorganization, ring‐flip preference, adaptability, and steric effects. Triple helix integrity was proven by crystal structure analysis and binding to HSP47.

Publications

[1] 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 (40), 6830. 10.1002/ejoc.201901206

[2] 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 (7), 1611. 10.1055/s-0037-1610673

[3] The Science Forum in Aachen: Joyful Expectations, H. G. Schmalz, CHEMKON, 2019, 26 (5), 177. 10.1002/ckon.201900048

[4] Total Synthesis of alpha-Tocopherol through Enantioselective Iridium-Catalyzed Fragmentation of a Spiro-Cyclobutanol Intermediate, F. Ratsch, W. Schlundt, D. Albat, A. Zimmer, J. M. Neudorfl, T. Netscher, H. G. Schmalz, Chem. Eur. J., 2019, 25 (19), 4941. 10.1002/chem.201900564

[5] Regeneration of ergothioneine after reaction with singlet oxygen, M. Oumari, B. Goldfuss, C. Stoffels, H. G. Schmalz, D. Grundemann, Free Radical Biol. Med., 2019, 134, 508. 10.1016/j.freeradbiomed.2019.01.043

[6] 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. Buttner, H. T. Li, M. Sattler, K. Hadian, J. Gopalakrishnan, EMBO J., 2019, 38 (2). 10.15252/embj.201899876

[7] 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 (3), 943. 10.1039/c8sc90247j

[8] A Stereoselective Synthesis of the ACE Inhibitor Trandolapril, S. Chiha, M. Spilles, J. M. Neudorfl, H. G. Schmalz, Synlett, 2019, 30 (7), 813. 10.1055/s-0037-1612306

[9] 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. 10.1016/j.antiviral.2019.104644

[10] Hydrogen Peroxide Sensors Based on Fluorescence Quenching of the 2-Aminobenzimidazole Fluorophore, M. Atar, O. Taspinar, S. Hanft, B. Goldfuss, H. G. Schmalz, A. G. Griesbeck, J. Org. Chem., 2019, 84 (24), 15972. 10.1021/acs.joc.9b02262

[11] Synthetic Indolactam V Analogues as Inhibitors of PAR2-Induced Calcium Mobilization in Triple-Negative Breast Cancer Cells, J. Stein, S. Stahn, J. M. Neudorfl, J. Sperlich, H. G. Schmalz, N. Teusch, ChemMedChem, 2018, 13 (2), 147. 10.1002/cmdc.201700640

[12] A bit of Pride may be, H. G. Schmalz, CHEMKON, 2018, 25 (1), 5. 10.1002/ckon.201880131

[13] 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 (6), 785. 10.1055/s-0036-1591528

[14] 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. Neudorfl, H. G. Schmalz, Chem. Eur. J., 2018, 24 (10), 2379. 10.1002/chem.201800042

[15] 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. Muller, J. Bruns, R. Opitz, J. M. Neudorfl, R. Kuhne, H. G. Schmalz, Eur. J. Org. Chem., 2018, 2018 (4), 455. 10.1002/ejoc.201701584

[16] 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. Schafer, V. Wewer, S. Metzger, E. Schomig, D. Grundemann, Free Radical Biol. Med., 2017, 113, 385. 10.1016/j.freeradbiomed.2017.10.372

[17] 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. 10.1016/j.ejmech.2017.09.055

[18] Chemistry Teaching in the Post-Factual Age, H. G. Schmalz, CHEMKON, 2017, 24 (1), 5. 10.1002/ckon.201710292

[19] Tandem Hydroalumination/Cu-Catalyzed Asymmetric Vinyl Metalation as a New Access to Enantioenriched Vinylcyclopropane Derivatives, D. S. Muller, V. Werner, S. Akyol, H. G. Schmalz, I. Marek, Org. Lett., 2017, 19 (15), 3970. 10.1021/acs.orglett.7b01661

[20] 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. 10.1016/j.ejmech.2016.11.020

[21] Organocatalyzed Synthesis of Oleochemical Carbonates from CO2 and Renewables, H. Buttner, J. Steinbauer, C. Wulf, M. Dindaroglu, H. G. Schmalz, T. Werner, ChemSusChem, 2017, 10 (6), 1076. 10.1002/cssc.201601163

[22] Methyl Fumarate-Derived Iron Carbonyl Complexes (FumET-CORMs) as Powerful Anti-inflammatory Agents, B. Bauer, A. L. Goderz, H. Braumuller, J. M. Neudorfl, M. Rocken, T. Wieder, H. G. Schmalz, ChemMedChem, 2017, 12 (23), 1927. 10.1002/cmdc.201700488

[23] Immune modulatory effects of methyl fumarate-derived iron carbonyl complexes, B. Bauer, A. Goderz, H. Braumuller, M. Rocken, T. Wieder, H. Schmalz, Exp. Dermatol., 2017, 26 (3), E52.

[24] CO-releasing fumarate complexes show superior anti-inflammatory effects compared to dimethyl fumarate treatment, B. Bauer, A. Goderz, H. Braumuller, M. Rocken, W. Thomas, H. Schmalz, J. Invest. Dermatol., 2017, 137 (10), S262. 10.1016/j.jid.2017.07.607

[25] 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 (2), 188. 10.1021/acsmedchemlett.5b00418

[26] 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. Controlled Release, 2016, 239, 128. 10.1016/j.jconrel.2016.08.030

[27] 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 (34), 5620. 10.1002/ejoc.201601069

[28] CHEMISTRY A molecular shuttle for hydrogen cyanide, H. G. Schmalz, Science, 2016, 351 (6275), 817. 10.1126/science.aaf2215

[29] Chemistry Education as a Contribution and Opportunity to social Integration, H. G. Schmalz, CHEMKON, 2016, 23 (1), 5. 10.1002/ckon.201610268

[30] Low-Pressure Cobalt-Catalyzed Enantioselective Hydrovinylation of Vinylarenes, S. Movahhed, J. Westphal, M. Dindaroglu, A. Falk, H. G. Schmalz, Chem. Eur. J., 2016, 22 (22), 7381. 10.1002/chem.201601283

[31] Total Synthesis of the Antiviral Natural Product Houttuynoid B, T. Kerl, F. Berger, H. G. Schmalz, Chem. Eur. J., 2016, 22 (9), 2935. 10.1002/chem.201505118

[32] 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. Hulskamp, A. Schrader, BMC Plant Biol., 2016, 16. 10.1186/s12870-016-0880-7

[33] Synthesis of New Sulfur-Containing Derivatives of Furanoallocolchicinoids, Y. A. Gracheva, H. G. Schmalz, E. V. Svirshchevskaya, A. Y. Fedorov, Rus. J. Org. Chem., 2016, 52 (8), 1137. 10.1134/s1070428016080078

[34] 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 (23), 5167. 10.1002/ejoc.201500573

[35] 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 (2), 692. 10.1021/jm501678w

[36] 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 (12), 2158. 10.1039/c5md00320b

[37] 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, Rus. Chem. Bull., 2015, 64 (6), 1362. 10.1007/s11172-015-1018-z

[38] 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. Ed., 2015, 54 (42), 12314. 10.1002/anie.201502445

[39] 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. Neudorfl, R. Kuhne, H. G. Schmalz, Chem. Eur. J., 2015, 21 (23), 8464. 10.1002/chem.201406493

[40] 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. Hirschhauser, P. Mayer, C. Frias, C. D. Herling, M. Hallek, H. G. Schmalz, A. Prokop, D. Mougiakakos, M. Herling, Mol. Cancer, 2015, 14. 10.1186/s12943-015-0378-1

[41] A modular toolkit to inhibit proline-rich motif-mediated protein-protein interactions, R. Opitz, M. Muller, 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. Kuhne, PNAS, 2015, 112 (16), 5011. 10.1073/pnas.1422054112

[42] 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 (23), 3717. 10.1055/s-0034-1378876

[43] 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. Schafer, Eur. J. Mass Spectrom., 2015, 21 (3), 623. 10.1255/ejms.1310

[44] 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. Cat., 2015, 357 (14-15), 3317. 10.1002/adsc.201500644

[45] Biomimetic Synthesis of Isoindolinones Related to the Marilines, D. Augner, H. G. Schmalz, Synlett, 2015, 26 (10), 1395. 10.1055/s-0034-1380700

[46] 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 (16), 3337. 10.1002/ejoc.201402240

[47] 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 (38), 12051. 10.1002/chem.201404379

[48] 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. Kramer, W. van Son, M. Seelen, H. G. Schmalz, A. Schmidt, M. Hafner, B. A. Yard, Redox Biol., 2014, 2, 739. 10.1016/j.redox.2014.06.002

[49] 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. Neudorfl, N. Schlorer, R. Kuhne, H. G. Schmalz, Eur. J. Org. Chem., 2014, 2014 (29), 6467. 10.1002/ejoc.201402737

[50] 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. Neudorfl, H. Sutorius, A. Prokop, V. V. Fokin, H. G. Schmalz, A. Y. Fedorov, Eur. J. Org. Chem., 2014, 2014 (29), 6481. 10.1002/ejoc.201402850

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

[52] 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. Neudorfl, R. Kuhne, H. G. Schmalz, Eur. J. Org. Chem., 2014, 2014 (13), 2664. 10.1002/ejoc.201301875

[53] 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 (23), 8664. 10.1039/c4dt00254g

[54] 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 (12), 6035. 10.1039/c3ra47000h

[55] Aryl-Phenyl Scrambling in Intermediate Organopalladium Complexes: A Gas-Phase Study of the Mizoroki-Heck Reaction, L. Fiebig, N. Schlorer, H. G. Schmalz, M. Schafer, Chem. Eur. J., 2014, 20 (17), 4906. 10.1002/chem.201400115

[56] Synthesis of C-2-Symmetric Bisphosphine Ligands from Tartaric Acid, and Their Performance in the Pd-Catalyzed Asymmetric O-Allylation of a Phenol, M. Dindaroglu, A. Dincer, H. G. Schmalz, Eur. J. Org. Chem., 2014, 2014 (20), 4315. 10.1002/ejoc.201402326

[57] Structure-Activity Relationships of Novel 2-Benzyl-3-Phenylisoindolinones as Inhibitors of Cholesterol Esterase, M. Steinkruger, D. Augner, T. Mielke, M. Gutschow, S. Herzig, H. G. Schmalz, M. Pietsch, Naunyn-Schmiedeberg's Arch. Pharmacol., 2013, 386, S80.

[58] 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. Kramer, H. G. Schmalz, B. A. Yard, Transpl. Int., 2013, 26, 56.

[59] Identification and Kinetic Characterization of Novel Inhibitors of Human Cholesterol Esterase as Anti-Atherosclerotic Agents, M. Sheikh, M. Steinkruger, D. Augner, M. Gutschow, S. Herzig, H. G. Schmalz, M. Pietsch, Naunyn-Schmiedeberg's Arch. Pharmacol., 2013, 386, S78.

[60] 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. Kramer, M. Hafner, S. Amslinger, H. G. Schmalz, B. A. Yard, Free Radical Biol. Med., 2013, 65, 78. 10.1016/j.freeradbiomed.2013.06.014

[61] 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, Rus. J. Bioorg. Chem., 2013, 39 (5), 543. 10.1134/s1068162013050105

[62] Nucleoside Analogues with a 1,3-Diene-Fe(CO)(3) Substructure: Stereoselective Synthesis, Configurational Assignment, and Apoptosis-Inducing Activity, C. Hirschhauser, J. Velcicky, D. Schlawe, E. Hessler, A. Majdalani, J. M. Neudorfl, A. Prokop, T. Wieder, H. G. Schmalz, Chem. Eur. J., 2013, 19 (39), 13017. 10.1002/chem.201301672

[63] 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. Neudorfl, R. Kuhne, H. G. Schmalz, Angew. Chem. Int. Ed., 2013, 52 (36), 9539. 10.1002/anie.201302014

[64] 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. Schafer, J. Org. Chem., 2013, 78 (20), 10485. 10.1021/jo402001g

[65] Enantioselective Nickel-Catalyzed Hydrocyanation of Vinylarenes Using Chiral Phosphine-Phosphite Ligands and TMS-CN as a Source of HCN, A. Falk, A. L. Goderz, H. G. Schmalz, Angew. Chem. Int. Ed., 2013, 52 (5), 1576. 10.1002/anie.201208082

[66] A Scalable Synthesis of Chiral Modular Phosphine-Phosphite Ligands, M. Dindaroglu, A. Falk, H. G. Schmalz, Synthesis, 2013, 45 (4), 527. 10.1055/s-0032-1316847

[67] 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. Neudorfl, A. Burke, H. G. Schmalz, Tetrahedron: Asymmetry, 2013, 24 (11), 657. 10.1016/j.tetasy.2013.04.008

[68] 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. Neudorfl, B. Yard, H. G. Schmalz, Organometallics, 2013, 32 (13), 3587. 10.1021/om301233h

[69] 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. Kronke, H. G. Schmalz, J. Nat. Prod., 2013, 76 (8), 1519. 10.1021/np400301d

[70] Synthesis of Oxa-B-Ring Analogs of Colchicine through Rh-Catalyzed Intramolecular 5+2 Cycloaddition, A. O. Termath, S. Ritter, M. Konig, D. P. Kranz, J. M. Neudorfl, A. Prokop, H. G. Schmalz, Eur. J. Org. Chem., 2012, 2012 (24), 4501. 10.1002/ejoc.201200677

[71] 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 (10), 1134. 10.1097/00007890-201211271-02252

[72] Total Synthesis of Indole-Derived Allocolchicine Analogues Exhibiting Strong Apoptosis-Inducing Activity, N. Sitnikov, J. Velder, L. Abodo, N. Cuvelier, J. Neudorfl, A. Prokop, G. Krause, A. Y. Fedorov, H. G. Schmalz, Chem. Eur. J., 2012, 18 (38), 12096. 10.1002/chem.201200083

[73] 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. Neudorfl, M. Menning, T. A. Kufer, H. G. Schmalz, MedChemComm, 2012, 3 (11), 1377. 10.1039/c2md20221b

[74] Iron Dienylphosphate Tricarbonyl Complexes as Water-Soluble Enzyme-Triggered CO-Releasing Molecules (ET-CORMs), S. Romanski, H. Rucker, E. Stamellou, M. Guttentag, J. M. Neudorfl, R. Alberto, S. Amslinger, B. Yard, H. G. Schmalz, Organometallics, 2012, 31 (16), 5800. 10.1021/om300359a

[75] 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. Rucker, A. Adler, J. M. Neudorfl, R. Alberto, S. Amslinger, H. G. Schmalz, Dalton Trans., 2012, 41 (45), 13862. 10.1039/c2dt30662j

[76] 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 (6), 1179. 10.1002/ejoc.201101258

[77] An Enantioselective Total Synthesis of Helioporins C and E, W. Lolsberg, S. Werle, J. M. Neudorfl, H. G. Schmalz, Org. Lett., 2012, 14 (23), 5996. 10.1021/ol302898h

[78] Molecular Oxygen as a Redox Catalyst in Intramolecular Photocycloadditions of Coumarins, D. P. Kranz, A. G. Griesbeck, R. Alle, R. Perez-Ruiz, J. M. Neudorfl, K. Meerholz, H. G. Schmalz, Angew. Chem. Int. Ed., 2012, 51 (24), 6000. 10.1002/anie.201201222

[79] Synthesis of B-Ring-Modified Steroids through BF3-Promoted Rearrangement/Substitution of 6 beta-Hydroxy-5,19-cyclosteroids, D. P. Kranz, S. Chiha, A. M. Z. Greffen, J. M. Neudorfl, H. G. Schmalz, Org. Lett., 2012, 14 (14), 3692. 10.1021/ol301532w

[80] 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 (21), 6396. 10.1039/c2dt12211a

[81] 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 (9), 2338. 10.1021/ol300757m

[82] TADDOL-Based Phosphane-Phosphite Ligands in Enantioselective Cu-Catalyzed Grignard 1,4-Additions Followed by Mannich-Type Alkylations, M. Drusan, W. Lolsberg, A. Skvorcova, H. G. Schmalz, R. Sebesta, Eur. J. Org. Chem., 2012, 2012 (31), 6285. 10.1002/ejoc.201200729

[83] Ligand Control of the Cobalt-Catalysed 1,4-Hydrovinylation Reaction, M. Arndt, M. Dindaroglu, H. G. Schmalz, G. Hilt, Synthesis, 2012, 44 (22), 3534. 10.1055/s-0032-1316796

[84] 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 (18), 6948. 10.1021/ja201743j

[85] Metal-Free Intramolecular Carbonyl-Olefin Metathesis of ortho-Prenylaryl Ketones, A. Soicke, N. Slavov, J. M. Neudorfl, H. G. Schmalz, Synlett, 2011, (17), 2487. 10.1055/s-0030-1260320

[86] Enantioselective Access to 3-Methylene-1H-indanol through Asymmetric Domino Allylstannylation-Heck Reaction, J. Schutte, S. T. Ye, H. G. Schmalz, Synlett, 2011, (18), 2725. 10.1055/s-0031-1289539

[87] (RS)-Tricarbonyl(eta(4)-1,3-diacetoxy-5,5-dimethylcyclohexa-1,3-diene) iron(0), S. Romanski, J. M. Neudorfl, H. G. Schmalz, Acta Crystallogr., Sect. E: Struct. Rep. Online, 2011, 67, M1530. 10.1107/s1600536811041298

[88] 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. Neudorfl, S. Amslinger, H. G. Schmalz, Angew. Chem. Int. Ed., 2011, 50 (18).

[89] Acyloxybutadiene Iron Tricarbonyl Complexes as Enzyme-Triggered CO-Releasing Molecules (ET-CORMs), S. Romanski, B. Kraus, U. Schatzschneider, J. M. Neudorfl, S. Amslinger, H. G. Schmalz, Angew. Chem. Int. Ed., 2011, 50 (10), 2392. 10.1002/anie.201006598

[90] 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. Neudorfl, R. Kuhne, H. G. Schmalz, Chem. Eur. J., 2011, 17 (43), 12037. 10.1002/chem.201101704

[91] 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 (2), 1585. 10.3987/com-10-s(e)117

[92] Total Synthesis of cyclo-Mumbaistatin Analogues through Anionic Homo-Fries Rearrangement, S. Neufeind, N. Hulsken, J. M. Neudorfl, N. Schlorer, H. G. Schmalz, Chem. Eur. J., 2011, 17 (9), 2633. 10.1002/chem.201003166

[93] Chiral phosphine-phosphite ligands in the enantioselective 1,4-addition of Grignard reagents to alpha,beta-unsaturated carbonyl compounds, Q. Naeemi, T. Robert, D. P. Kranz, J. Velder, H. G. Schmalz, Tetrahedron: Asymmetry, 2011, 22 (8), 887. 10.1016/j.tetasy.2011.04.018

[94] 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. Neudorfl, H. G. Schmalz, Eur. J. Org. Chem., 2011, 2011 (15), 2860. 10.1002/ejoc.201100020

[95] Stereoselective Synthesis and Biological Evaluation of Ferrocene-Containing 5-Hydroxyeicosatetraenoic Acid Analogues, N. Kausch-Busies, J. M. Neudorfl, P. Wefelmeier, A. Prokop, H. Kuhn, H. G. Schmalz, Eur. J. Org. Chem., 2011, 2011 (24), 4634. 10.1002/ejoc.201100003

[96] Synthesis and First Biological Evaluation of an Iron-Containing HETE Analogue, N. Kausch-Busies, B. Kater, J. M. Neudorfl, A. Prokop, H. G. Schmalz, Eur. J. Org. Chem., 2011, 2011 (6), 1133. 10.1002/ejoc.201001445

[97] 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 (4), 639. 10.1007/s00432-010-0924-6

[98] Practical One-Pot Double Functionalizations of Proline, P. Huy, H. G. Schmalz, Synthesis, 2011, (6), 954. 10.1055/s-0030-1258428

[99] A Practical Synthesis of Trans-3-Substituted Proline Derivatives through 1,4-Addition, P. Huy, J. M. Neudorfl, H. G. Schmalz, Org. Lett., 2011, 13 (2), 216. 10.1021/ol102613z

[100] Heck coupling in the gas phase: Examination of the reaction mechanism by ion/molecule reactions and mass spectrometry, L. Fiebig, H. G. Schmalz, M. Schafer, Int. J. Mass Spectrom., 2011, 308 (2-3), 307. 10.1016/j.ijms.2011.07.013

[101] 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. Neudorfl, A. Adler, H. G. Schmalz, Adv. Synth. Cat., 2011, 353 (18), 3357. 10.1002/adsc.201100658

[102] Paraoxonase-1 is a major determinant of clopidogrel efficacy, H. J. Bouman, E. Schomig, J. W. van Werkum, J. Velder, C. M. Hackeng, C. Hirschhauser, C. Waldmann, H. G. Schmalz, J. M. ten Berg, D. Taubert, Nat. Med., 2011, 17 (1), 110. 10.1038/nm.2281

[103] Paraoxonase-1 is a major determinant of clopidogrel efficacy (vol 17, pg 110, 2011), H. J. Bouman, E. Schomig, J. W. van Werkum, J. Velder, C. M. Hackeng, C. Hirschhauser, C. Waldmann, H. G. Schmalz, J. M. ten Berg, D. Taubert, Nat. Med., 2011, 17 (9), 1153.

[104] Paraoxonase-1 and clopidogrel efficacy reply, H. J. Bouman, E. Schomig, J. W. van Werkum, J. Velder, C. M. Hackeng, C. Hirschhauser, C. Waldmann, H. G. Schmalz, J. M. ten Berg, D. Taubert, Nat. Med., 2011, 17 (9), 1042. 10.1038/nm.2469

[105] 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. Ed., 2011, 50 (41), 9689. 10.1002/anie.201103613

[106] N-Capping of Primary Amines with 2-Acyl-benzaldehydes To Give Isoindolinones, D. Augner, D. C. Gerbino, N. Slavov, J. M. Neudorfl, H. G. Schmalz, Org. Lett., 2011, 13 (19), 5374. 10.1021/ol202271k

[107] 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 (23), 6236. 10.1021/ol202696n

[108] 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. Muller, H. Oschkinat, R. Kuhne, H. G. Schmalz, Angew. Chem. Int. Ed., 2010, 49 (39), 7111. 10.1002/anie.201001739

[109] A Scalable Synthesis of (+/-)-2-Oxoclopidogrel, J. Velder, C. Hirschhauser, C. Waldmann, D. Taubert, H. J. Bouman, H. G. Schmalz, Synlett, 2010, (3), 467. 10.1055/s-0029-1219177

[110] Total Synthesis of the Marine Antibiotic Pestalone and its Surprisingly Facile Conversion into Pestalalactone and Pestalachloride A, N. Slavov, J. Cvengros, J. M. Neudorfl, H. G. Schmalz, Angew. Chem. Int. Ed., 2010, 49 (41), 7588. 10.1002/anie.201003755

[111] Asymmetric Hydroformylation Using Taddol-Based Chiral Phosphine-Phosphite Ligands, T. Robert, Z. Abiri, J. Wassenaar, A. J. Sandee, S. Romanski, J. M. Neudorfl, H. G. Schmalz, J. N. H. Reek, Organometallics, 2010, 29 (2), 478. 10.1021/om9009735

[112] 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 (21-22), 2671. 10.1016/j.tetasy.2010.10.026

[113] Potassium (1-methoxycarbonyl-2-methylprop-2-en-2-ylidene)azinate, C. Reuter, J. M. Neudorfl, H. G. Schmalz, Acta Crystallogr., Sect. E: Struct. Rep. Online, 2010, 66, M461. 10.1107/s1600536810010159

[114] 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. Neudorfl, A. Prokop, H. Oschkinat, H. G. Schmalz, ChemMedChem, 2010, 5 (5), 661. 10.1002/cmdc.201000063

[115] Synthesis of Novel Allocolchicine Analogues with a Pyridine C-Ring through Intermolecular Vollhardt Diyne-Nitrile Cyclotrimerization, N. Nicolaus, H. G. Schmalz, Synlett, 2010, (14), 2071. 10.1055/s-0030-1258512

[116] 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. Cat., 2010, 352 (11-12), 2023. 10.1002/adsc.201000213

[117] 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. Neudorfl, H. G. Schmalz, Tetrahedron: Asymmetry, 2010, 21 (13-14), 1745. 10.1016/j.tetasy.2010.05.019

[118] New caspase-independent but ROS-dependent apoptosis pathways are targeted in melanoma cells by an iron-containing cytosine analogue, J. C. Franke, M. Plotz, A. Prokop, C. C. Geilen, H. G. Schmalz, J. Eberle, Biochem. Pharmacol., 2010, 79 (4), 575. 10.1016/j.bcp.2009.09.022

[119] New caspase-independent but ROS-dependent apoptosis pathways are targeted in melanoma cells by an iron-containing cytosine analogue, J. C. Franke, M. Plotz, C. C. Geilen, H. Schmalz, A. Prokop, J. Eberle, Exp. Dermatol., 2010, 19 (2), 211.

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

[121] 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. Kronke, H. G. Schmalz, T. A. Kufer, ChemMedChem, 2010, 5 (12), 2065. 10.1002/cmdc.201000320

[122] trans-1,2-Bis(3,5-dimethoxyphenyl)ethene, S. Ritter, J. M. Neudorfl, J. Velder, H. G. Schmalz, Acta Crystallogr., Sect. E: Struct. Rep. Online, 2009, 65, O2150. 10.1107/s160053680903116x

[123] trans-Ethylenedi-p-phenylene diacetate, S. Ritter, J. M. Neudorfl, J. Velder, H. G. Schmalz, Acta Crystallogr., Sect. E: Struct. Rep. Online, 2009, 65, O2229. 10.1107/s1600536809032620

[124] A 2+2+2 -Cycloaddition Approach toward 6-Oxa-allocolchicinoids with Apoptosis-inducing Activity, N. Nicolaus, S. Strauss, J. M. Neudorfl, A. Prokop, H. G. Schmalz, Org. Lett., 2009, 11 (2), 341. 10.1021/ol802542c

[125] Stereoselective Synthesis of New Ferrocene-Derived Amino Acid Building Blocks, A. Hunold, I. Neundorf, P. James, J. Neudorfl, H. G. Schmalz, Eur. J. Org. Chem., 2009, 2009 (26), 4429. 10.1002/ejoc.200900552

[126] 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. Podesta, Eur. J. Org. Chem., 2009, 2009 (23), 3964. 10.1002/ejoc.200900234

[127] 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. Schutte, N. Schlorer, J. Neudorfl, H. G. Schmalz, Angew. Chem. Int. Ed., 2009, 48 (33), 6148. 10.1002/anie.200901837

[128] 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. Neudorfl, J. Lex, H. G. Schmalz, Adv. Synth. Cat., 2008, 350 (9), 1309. 10.1002/adsc.200800146

[129] 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. Ed., 2008, 47 (40), 7718. 10.1002/anie.200803247

[130] 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. Neudorfl, J. Lex, H. G. Schmalz, Synlett, 2008, (9), 1361. 10.1055/s-2008-1072771

[131] The iron-containing nucleoside analogue N69 efficiently induces apoptosis inhuman melanoma cells by activating new pathways enclosing lysosomalactivation, J. C. Franke, A. Prokop, D. Schlawe, H. Schmalz, J. Eberle, Exp. Dermatol., 2008, 17 (3), 278.

[132] Microwave-assisted cleavage of aryl methyl ethers with lithium thioethoxide (LiSEt), J. Cvengros, S. Neufeind, A. Becker, H. G. Schmalz, Synlett, 2008, (13), 1993. 10.1055/s-2008-1077949

[133] Enantioselective Synthesis of a trans-7,8-Dimethoxycalamenene, S. Werle, T. Fey, J. M. Neudorfl, H. G. Schmalz, Org. Lett., 2007, 9 (18), 3555. 10.1021/ol071228v

[134] Enantioselective synthesis of a trans-7,8-dimethoxycalamenene (vol 9, pg 3556, 2007), S. Werle, T. Fey, J. M. Neudorfl, H. G. Schmalz, Org. Lett., 2007, 9 (20), 4085. 10.1021/ol702069a

[135] Synthesis of a mumbaistatin analogue through cross-coupling, D. Sucunza, D. Dembkowski, S. Neufeind, J. Velder, J. Lex, H. G. Schmalz, Synlett, 2007, (16), 2569. 10.1055/s-2007-986652

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

[137] 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 (24), 3991. 10.1002/ejoc.200700342

[138] 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 (8), 2857. 10.1021/jo062447h

[139] Synthesis of the core structure of the cyclocitrinols via SmI(2)-mediated fragmentation of a cyclopropane precursor, S. El Sheikh, A. M. Z. Greffen, J. Lex, J. M. Neudorfl, H. G. Schmalz, Synlett, 2007, (12), 1881. 10.1055/s-2007-984521

[140] 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. Ed., 2006, 45 (40), 6704. 10.1002/anie.200601252

[141] A simple access to biologically important trans-stilbenes via Ru-catalyzed cross metathesis, J. Velder, S. Ritter, J. Lex, H. G. Schmalz, Synthesis, 2006, (2), 273. 10.1055/s-2005-918506

[142] 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 (16), 4228. 10.1016/j.bmcl.2006.05.077

[143] 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, (19), 3309. 10.1055/s-2006-951555

[144] 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 (11), 179B. 10.1182/blood.V108.11.4404.4404

[145] 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 (11), 178B. 10.1182/blood.V108.11.4403.4403

[146] Enantioselective synthesis of ferrocenyl nucleoside analogues with apoptosis-inducing activity, P. James, J. Neudorfl, M. Eissmann, P. Jesse, A. Prokop, H. G. Schmalz, Org. Lett., 2006, 8 (13), 2763. 10.1021/ol060868f

[147] 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. Neudorfl, H. G. Schmalz, Synlett, 2006, (10), 1527. 10.1055/s-2006-941599

[148] Microwave-assisted amination of a chloropurine derivative in the synthesis of acyclic nucleoside analogues, A. Lanver, H. G. Schmalz, Molecules, 2005, 10 (2), 508. 10.3390/10020508

[149] A Pauson-Khand approach to new carbocyclic nucleoside analogs, A. Lanver, H. G. Schmalz, Eur. J. Org. Chem., 2005, 2005 (7), 1444. 10.1002/ejoc.200400886

[150] 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 (22), 4904. 10.1002/ejoc.200500481

[151] Total synthesis of (-)-colchicine via a Rh-triggered cycloaddition cascade, T. Graening, V. Bette, J. Neudorfl, J. Lex, H. G. Schmalz, Org. Lett., 2005, 7 (20), 4317. 10.1021/ol051316k

[152] 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 (20), 5087. 10.1002/chem.200400079

[153] 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. Ed., 2004, 43 (13), 1731. 10.1002/anie.200353132

[154] 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 (11), 574A. 10.1182/blood.V104.11.2085.2085

[155] Application of chromium-arene complexes in the organic synthesis. Efficient synthesis of stilbene phytoalexins, K. E. Polunin, H. G. Schmalz, Rus. J. Coord. Chem., 2004, 30 (4), 252. 10.1023/B:RUCO.0000022800.70211.7d

[156] Michael additions of aldehydes and ketones to beta-nitrostyrenes in an ionic liquid, P. Kotrusz, S. Toma, H. G. Schmalz, A. Adler, Eur. J. Org. Chem., 2004, 2004 (7), 1577. 10.1002/ejoc.200300648

[157] Total syntheses of colchicine in comparison: A journey through 50 years of synthetic organic chemistry, T. Graening, H. G. Schmalz, Angew. Chem. Int. Ed., 2004, 43 (25), 3230. 10.1002/anie.200300615

[158] Halogen-lithium exchange reactions under in situ-quench conditions: A powerful concept for organic synthesis, S. El Sheikh, H. G. Schmalz, Curr. Opin. Drug Discovery Dev., 2004, 7 (6), 882.

[159] 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. Bottcher, B. Gotov, Synlett, 2003, (12), 1783. 10.1055/s-2003-41492

[160] 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, (12), 1851. 10.1055/s-2003-41030

[161] 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 (18), 3201. 10.1016/s0040-4020(03)00427-7

[162] Synthetic analogues of the antibiotic pestalone, F. Kaiser, H. G. Schmalz, Tetrahedron, 2003, 59 (37), 7345. 10.1016/s0040-4020(03)01136-0

[163] Pd-catalyzed enantioselective allylic substitution: New strategic options for the total synthesis of natural products, T. Graening, H. G. Schmalz, Angew. Chem. Int. Ed., 2003, 42 (23), 2580. 10.1002/anie.200301644

[164] Catalytic-enantioselective methoxycarbonylation of 1,3-dichloroarene-tricarbonyl-chromium(0) complexes: A desymmetrization approach to planar chirality, A. Bottcher, H. G. Schmalz, Synlett, 2003, (11), 1595. 10.1055/s-2003-41417

[165] 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. Ed., 2002, 41 (14), 2525. 10.1002/1521-3773(20020715)41:14<2525::Aid-anie2525>3.0.Co;2-o

[166] An efficient organometallic approach to new carbocyclic nucleoside analogues, J. Velcicky, J. Lex, H. G. Schmalz, Org. Lett., 2002, 4 (4), 565. 10.1021/ol017181+

[167] 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. Ed., 2002, 41 (19), 3656. 10.1002/1521-3773(20021004)41:19<3656::Aid-anie3656>3.0.Co;2-7

[168] 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 (6), 1009. 10.1016/s0040-4039(01)02325-5

[169] 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 (19), 3507. 10.1016/s0040-4039(02)00571-3

[170] Electron transfer driven transformations of transition metal pi-complexes: Samarium(II) iodide mediated coupling of fluoroarene-Cr(CO)(3) complexes with ketones, H. G. Schmalz, O. Kiehl, B. Gotov, Synlett, 2002, (8), 1253. 10.1055/s-2002-32969

[171] Chromium arene complexes in synthesis of trans-resveratrol, K. E. Polunin, H. G. Schmalz, L. A. Polunina, Rus. Chem. Bull., 2002, 51 (7), 1319. 10.1023/a:1020921101384

[172] eta(6)-Arene-tricarbonylchromium complexes in the syntheses of trans-resveratrol and pinostilbene, K. E. Polunin, I. A. Polunina, H. G. Schmalz, Mendeleev Commun., 2002, (5), 178. 10.1070/MC2002v012n05ABEH001616

[173] 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 (26), 9248. 10.1021/jo026232t

[174] 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. Ed., 2002, 41 (9), 1524. 10.1002/1521-3773(20020503)41:9<1524::Aid-anie1524>3.0.Co;2-9

[175] 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, (2), 361.

[176] Pd-catalyzed carbonylative cross-coupling reactions of chloroarene-Cr(CO)(3) complexes, B. Gotov, J. Kaufmann, H. Schumann, H. G. Schmalz, Synlett, 2002, (7), 1161.

[177] 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 (22), 3915. 10.1021/ol026827a

[178] 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. Cat., 2002, 344 (8), 868. 10.1002/1615-4169(200209)344:8<868::Aid-adsc868>3.0.Co;2-m

[179] 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. Dorken, H. G. Schmalz, P. T. Daniel, G. Henze, Leukemia, 2001, 15 (11), 1735. 10.1038/sj.leu.2402284

[180] (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 (32), 5405. 10.1016/s0040-4039(01)01026-7

[181] 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. Dorken, H. G. Schmalz, G. Henze, P. T. Daniel, Blood, 2001, 98 (11), 220B.

[182] 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 (3), 446. 10.1039/b002898n

[183] 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 (24), 5325. 10.1002/1521-3765(20011217)7:24<5325::Aid-chem5325>3.0.Co;2-s

[184] On the antioxidative activity of several dihydropyridine derivatives, W. Gutwirth, M. Beer, T. Naumann, B. Lauven, K. Guttler, H. G. Schmalz, W. Klaus, Naunyn-Schmiedeberg's Arch. Pharmacol., 2001, 363 (4), R70.

[185] A catalytic-enantioselective entry to planar chiral pi-complexes: Enantioselective methoxycarbonylation of 1,2-dichlorobenzene-Cr(CO)(3), B. Gotov, H. G. Schmalz, Org. Lett., 2001, 3 (11), 1753. 10.1021/ol0159468

[186] 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 (22), 3579. 10.1021/ol016699a

[187] A modular approach to structurally diverse bidentate chelate ligands for transition metal catalysis, R. Kranich, K. Eis, O. Geis, S. Muhle, J. W. Bats, H. G. Schmalz, Chem. Eur. J., 2000, 6 (15), 2874. 10.1002/1521-3765(20000804)6:15<2874::Aid-chem2874>3.3.Co;2-t

[188] 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, (1), 69. 10.1039/a906935f

[189] 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. Ed., 1999, 38 (11), 1620. 10.1002/(sici)1521-3773(19990601)38:11<1620::Aid-anie1620>3.0.Co;2-1

[190] 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, (11), 1869.

[191] 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 (2), 537. 10.1002/(sici)1521-3765(19990201)5:2<537::Aid-chem537>3.0.Co;2-i

[192] Synthesis of an analog of the cytotoxic marine diterpene helioporin C exploiting arene-Cr(CO)(3) chemistry, D. Horstermann, H. G. Schmalz, G. Kociok-Kohn, Tetrahedron, 1999, 55 (22), 6905. 10.1016/s0040-4020(99)00346-4

[193] 2-aminobenzimidazolium nitrate at 152 K, a triclinic crystal structure with pronounced local pseudo-symmetry, J. W. Bats, D. Gordes, H. G. Schmalz, Acta Crystallogr., Sect. C: Cryst. Struct. Commun., 1999, 55, 1325. 10.1107/s0108270199004710

[194] 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, (12), 1883.

[195] Electron transfer driven reactions of transition metal pi-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 (37), 6683. 10.1016/s0040-4039(98)01436-1

[196] 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 (14), 3457. 10.1016/s0040-4020(98)00078-7

[197] 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 (1), 57. 10.1002/(sici)1521-3765(199801)4:1<57::Aid-chem57>3.0.Co;2-h

[198] Electron transfer driven addition of ketimine derived radicals to arene-Cr(CO)(3) complexes, O. Hoffmann, H. G. Schmalz, Synlett, 1998, (12), 1426.

[199] 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 (12), 1537. 10.1016/s0040-4039(98)00021-5

[200] 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 (12), 1541. 10.1016/s0040-4039(98)00020-3

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

[202] 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 (21), 7219. 10.1016/s0040-4020(97)00407-9

[203] 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. Ed., 1997, 36 (22), 2456. 10.1002/anie.199724561

[204] 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, (12), 2725. 10.1039/a703700g

[205] On the deprotonation of η6-1,3-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 (27), 9219. 10.1016/s0040-4020(97)00620-0

[206] Chiral η6-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 (26), 4545. 10.1016/s0040-4039(97)00995-7

[207] Enantioselective synthesis of the aglycones of pseudopterosin and seco-pseudopterosin via a common synthetic intermediate, A. Majdalani, H. G. Schmalz, Synlett, 1997, (11), 1303.

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

[209] Asymmetric induction in the nucleophile addition to η6-arene-tricarbonyl-chromium(0) complexes, M. F. Semmelhack, H. G. Schmalz, Tetrahedron Lett., 1996, 37 (18), 3089. 10.1016/0040-4039(96)00572-2

[210] Radical cyclization of η6-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 (17), 2947. 10.1016/0040-4039(96)00486-8

[211] Controlling the course of nucleophilic additions to ortho-substituted (η6-anisole)tricarbonyl-chromium complexes: Dienol ether formation versus tele-substitution, H. G. Schmalz, K. Schellhaas, Angew. Chem. Int. Ed., 1996, 35 (18), 2146. 10.1002/anie.199621461

[212] 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. Ed., 1995, 34 (21), 2383. 10.1002/anie.199523831

[213] 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 (31), 5515. 10.1016/0040-4039(95)01077-U

[214] 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 (31), 5511. 10.1016/0040-4039(95)01076-T

[215] 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 (27), 4777. 10.1016/0040-4039(95)00887-I

[216] Catalytic Ring‐Closing Metathesis: A New, Powerful Technique for Carbon–Carbon Coupling in Organic Synthesis, H. G. Schmalz, Angew. Chem. Int. Ed., 1995, 34 (17), 1833. 10.1002/anie.199518331

[217] Chemie in Deutschland ‐ Raus aus der Defensive, C. Bolm, B. Frauendorf, A. Griesbeck, U. Kliem, A. Kretschmer, H. C. Militzer, G. Muller, H. Perry, H. J. Rosenkranz, H. G. Schmalz, W. Schnick, A. D. Schluter, R. Stadler, S. Waffenschmidt, Nachr. Chem. Tech. Lab., 1995, 43 (9), 942. 10.1002/nadc.19950430909

[218] 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 (37), 6861. 10.1016/0040-4039(94)85024-0

[219] 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 (26), 4543. 10.1016/s0040-4039(00)60723-2

[220] 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., 1994, 33 (1), 109. 10.1002/anie.199401091

[221] Chromium Carbene Complexes in Organic Synthesis: Recent Developments and Perspectives, H. G. Schmalz, Angew. Chem. Int. Ed., 1994, 33 (3), 303. 10.1002/anie.199403031

[222] Enantioselektive Heck‐Reaktionen, H. G. Schmalz, Nachr. Chem. Tech. Lab., 1994, 42 (3), 270. 10.1002/nadc.19940420310

[223] Pd‐katalysierte Synthesen Vitamin‐D‐aktiver Verbindungen, H. G. Schmalz, Nachr. Chem. Tech. Lab., 1994, 42 (4), 394. 10.1002/nadc.19940420416

[224] Zr‐katalysierte Carbomagnesierungen von Alkenen, H. G. Schmalz, Nachr. Chem. Tech. Lab., 1994, 42 (7-8), 724. 10.1002/nadc.19940420715

[225] Eisenvermittelte Totalsynthese von Ikarugamycin, H. G. Schmalz, Nachr. Chem. Tech. Lab., 1994, 42 (10), 1016. 10.1002/nadc.19940421013

[226] Intramolekulare Alkoxypalladierungen, H. G. Schmalz, Nachr. Chem. Tech. Lab., 1994, 42 (12), 1267. 10.1002/nadc.19940421213

[227] 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 (26), 4547. 10.1016/s0040-4039(00)60724-4

[228] 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 (39), 6259. 10.1016/s0040-4039(00)73725-7

[229] 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. Ed., 1992, 31 (5), 631. 10.1002/anie.199206311

[230] 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 Ann. Chem., 1988, (4), 283. 10.1002/jlac.198819880402

[231] Total Synthesis of the Pseudoguaianolide (+)‐Confertin, G. Quinkert, H. G. Schmalz, Egonwalzer, T. Kowalczykprzewloka, G. Durner, J. W. Bats, Angew. Chem. Int. Ed., 1987, 26 (1), 61. 10.1002/anie.198700611

[232] 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. Ed., 1986, 25 (11), 992. 10.1002/anie.198609921

[233] (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. Ed., 1986, 25 (8), 732. 10.1002/anie.198607321

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UNIVERSITY OF COLOGNE

Faculty of Mathematics and Natural SciencesAG Schmalz

Recently Published

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

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

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

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

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

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

Scalable Synthesis of N,N′-Di(2,3-dihydroxy-propyl)-1,4-naphthalenedipropanamide and Its 1,4-Endoperoxide as a Singlet Oxygen-Releasing Molecule

ItaCORMs: conjugation with a CO-releasing unit greatly enhances the anti-inflammatory activity of itaconates

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

ET-CORM Mediated Vasorelaxation of Small Mesenteric Arteries: Involvement of Kv7 Potassium Channels

Some Surprising Transformations of Colchicone and Other Colchicine-Derived Tropolones

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

Improved Synthesis of MediPhos Ligands and their Use in the Pd-catalyzed Enantioselective N-Allylation of Glycine Esters

Abstract

Total Synthesis of (+)-Erogorgiaene and the Pseudopterosin A−F Aglycone via Enantioselective Cobalt-Catalyzed Hydrovinylation

Abstract

Enantioselective Total Synthesis and Structural Revision of Dysiherbol A

Abstract

A Concise Synthesis of 24,25-Dihydro-6-epi-Monanchosterol A

Abstract

A Short Enantioselective Synthesis of (S)-Levetiracetam through Direct Palladium-Catalyzed Asymmetric N-Allylation of Methyl 4-Aminobutyrate

Abstract

A General Stereocontrolled Synthesis of Opines via Asymmetric Pd‐Catalyzed N‐Allylation of Amino Acid Esters

Abstract

Enantioselective Cleavage of Cyclobutanols Through Ir‐Catalyzed C−C Bond Activation: Mechanistic and Synthetic Aspects

Abstract

Designed nanomolar small-molecule inhibitors of Ena/VASP EVH1 interaction impair invasion and extravasation of breast cancer cells

Abstract

Colchicine Alkaloids and Synthetic Analogues: Current Progress and Perspectives

Abstract

Synthesis of the 8,19-Epoxysteroid Eurysterol A

Abstract

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

Abstract

Triple‐Helix‐Stabilizing Effects in Collagen Model Peptides Containing PPII‐Helix‐Preorganized Diproline Modules

Abstract

Publications

Recently Published

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

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

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

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

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

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

Scalable Synthesis of N,N′-Di(2,3-dihydroxy-propyl)-1,4-naphthalenedipropanamide and Its 1,4-Endoperoxide as a Singlet Oxygen-Releasing Molecule

ItaCORMs: conjugation with a CO-releasing unit greatly enhances the anti-inflammatory activity of itaconates

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

ET-CORM Mediated Vasorelaxation of Small Mesenteric Arteries: Involvement of Kv7 Potassium Channels

Some Surprising Transformations of Colchicone and Other Colchicine-Derived Tropolones

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

Improved Synthesis of MediPhos Ligands and their Use in the Pd-catalyzed Enantioselective N-Allylation of Glycine Esters

Abstract

Total Synthesis of (+)-Erogorgiaene and the Pseudopterosin A−F Aglycone via Enantioselective Cobalt-Catalyzed Hydrovinylation

Abstract

Enantioselective Total Synthesis and Structural Revision of Dysiherbol A

Abstract

A Concise Synthesis of 24,25-Dihydro-6-epi-Monanchosterol A

Abstract

A Short Enantioselective Synthesis of (S)-Levetiracetam through Direct Palladium-Catalyzed Asymmetric N-Allylation of Methyl 4-Aminobutyrate

Abstract

A General Stereocontrolled Synthesis of Opines via Asymmetric Pd‐Catalyzed N‐Allylation of Amino Acid Esters

Abstract

Enantioselective Cleavage of Cyclobutanols Through Ir‐Catalyzed C−C Bond Activation: Mechanistic and Synthetic Aspects

Abstract

Designed nanomolar small-molecule inhibitors of Ena/VASP EVH1 interaction impair invasion and extravasation of breast cancer cells

Abstract

Colchicine Alkaloids and Synthetic Analogues: Current Progress and Perspectives

Abstract

Synthesis of the 8,19-Epoxysteroid Eurysterol A

Abstract

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

Abstract

Triple‐Helix‐Stabilizing Effects in Collagen Model Peptides Containing PPII‐Helix‐Preorganized Diproline Modules

Abstract

Publications

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