Total synthesis of tubulysin U and V.
Explore the source record for details and available documents.
Molecular Conformation↗
Biomedical subjects
Alexander Dömling
Publications and source records attributed to Alexander Dömling.
Desosamine in multicomponent reactions.
Desosamine occurring ubiquitously in natural products is introduced into isocyanide based multicomponent reaction chemistry. Corresponding products are of potential interest for the design of novel antibiotics.
Amino Sugars↗
Towards erythropoietin mimicking small molecules.
Small molecules potentially mimicking the hormone erythropoietin have been discovered by screening of a library of rationally designed multicomponent reaction molecules in a functional cell-based assay.
Animals↗
Biological evaluation of tubulysin A: a potential anticancer and antiangiogenic natural product.
Tubulysin A (tubA) is a natural product isolated from a strain of myxobacteria that has been shown to depolymerize microtubules and induce mitotic arrest. The potential of tubA as an anticancer and antiangiogenic agent is explored in the present study. tubA shows potent antiproliferative activity in a panel of human cancer cell lines irrespective of their multidrug resistance properties. It induces apoptosis in cancer cells but not in normal cells and shows significant potential antiangiogenic properties in several in vitro assays. It is efficacious in initial animal studies using a hollow fibre assay with 12 different human tumour cell lines. This study suggests that both in vitro and preclinical profiles of tubA may translate into clinically useful anticancer properties.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Design and modular parallel synthesis of a MCR derived alpha-helix mimetic protein-protein interaction inhibitor scaffold.
A terphenyl alpha-helix mimetic scaffold recognized to be capable of disrupting protein-protein interactions was structurally morphed into an easily amenable and versatile multicomponent reaction (MCR) backbone. The design, modular in-parallel library synthesis, initial cell based biological data, and preliminary in vitro screening for the disruption of the Bcl-w/Bak protein-protein interaction by representatives of the MCR derived scaffold are presented.
Apoptosis↗
Recent developments in isocyanide based multicomponent reactions in applied chemistry.
Explore the source record for details and available documents.
Chemistry, Pharmaceutical↗
Myxobacterial epothilones and tubulysins as promising anticancer agents.
Tubulin-binding agents play a pivotal role in current cancer therapy and there are many efforts in pre-clinical and clinical development of known and novel cytotoxic agents ongoing. In this article a known class, epothilones, as well as a novel class, tubulysins, are presented.
Antineoplastic Agents↗
Novel nonpeptidic inhibitors of HIV-1 protease obtained via a new multicomponent chemistry strategy.
Using a newly developed multicomponent chemistry strategy in combination with structure based drug design, a new class of HIV-1 protease inhibitors has been obtained.
Binding Sites↗
Highly substituted pyrrolidinones and pyridones by 4-CR/2-CR sequence.
[reaction: see text] By combining a Ugi four-component reaction of isocyanides, phosphonoacetic acids, primary amines, and glyoxals or alternatively 3-keto aldehydes with a subsequent Wittig ring-closing reaction (using the Horner/Wadsworth/Emmons variant (HWE)), highly substituted 5-oxo-2,5-dihydro-1H-pyrrole-2-carboxylic acid amides and 6-oxo-1,2,3,6-tetrahydro-pyridine-2-carboxylic acid amides can be assembled, respectively. The corresponding tandem of a Passerini reaction on 3-keto aldehydes and subsequent Wittig ring closure does not afford the expected six-membered 6-oxo-3,6-dihydro-2H-pyran-2-carboxylic acid amides but instead leads to the formation of 4-oxo-pent-2-enoic acid amides via an elimination route.
Journal Article↗
Massive parallel catalyst screening: toward asymmetric MCRs.
[reaction: see text]. Hundreds of Lewis acid/ligand combinations have been screened for stereochemical induction in the Passerini multicomponent reaction. The combination of titan tetraisopropylate and (4S,5S)-4,5-bis(diphenylhydroxymethyl)-2,2-dimethyldioxolane was found to give enantiomeric excesses between 32% and 42% in several examples. The absolute stereo induction of one example was determined chemically and by means of X-ray crystallography. This comprises the first asymmetric Passerini reaction and the first example of a stereochemical induction in an isocyanide based multicomponent reaction by a chiral Lewis acid.
Journal Article↗
Short and diverse route toward complex natural product-like macrocycles.
[reaction: see text] A general strategy toward macrocyclic compounds using multicomponent reaction (MCR) chemistry, e.g., Passerini and Ugi variants, and ring-closing metathesis (RCM) is introduced. The corresponding bifunctional isocyanides carboxylic acids bearing a terminal olefin are easy to prepare from the corresponding commercially available starting materials. Advantageously, this strategy allows fast access to a diverse conformational space of natural product-like macrocycles and could thus be of interest in the discovery of novel bioactive agents.
Alkenes↗
New MCRs: the first 4-component reaction leading to 2,4-disubstituted thiazoles.
New organic reactions allow chemical transformations which were previously not possible. Therefore, new reactions are important contributions to the progress in the field of organic synthesis. In this series we describe the design, scope, and limitations of newly-discovered multi-component reactions (MCRs). Herein, a first example of a MCR is introduced which allows general access to the class of 2,4-di- and 2,4,5-trisubstituted thiazoles.
Combinatorial Chemistry Techniques↗
Recent advances in isocyanide-based multicomponent chemistry.
Multicomponent reactions (MCRs) provide a powerful tool towards the one-pot synthesis of diverse and complex compounds on the one hand and small and 'drug-like' heterocycles on the other hand. No other single synthesis technology enables chemists to search such large chemical spaces as provided by MCRs. MCRs that involve isocyanides are by far the most versatile reactions in terms of scaffolds and number of accessible compounds.
Combinatorial Chemistry Techniques↗
Parallel synthesis of arrays of amino-acid-derived isocyanoamides useful as starting materials in IMCR.
Arrays of amino-acid-derived isocyanoamides are conveniently produced on a multigram scale in one step by the solventless aminolysis of the corresponding methyl esters with primary or secondary aliphatic amines. Most of the corresponding isocyanides precipitate during the reaction and can be filtered to yield highly pure, colorless, and odorless solids. They are potentially useful in the combinatorial chemistry of multicomponent reactions.
Amides↗