Synthesis of 12-aza analogs of epothilones and (E)-9,10-dehydroepothilones

Autor:	Bernhard Pfeiffer, Fabian Feyen, Kurt Hauenstein, Andrea Jantsch, Karl-Heinz Altmann
Rok vydání:	2008
Předmět:	chemistry.chemical_classification Ketone Diene Stereochemistry Carboxylic acid Organic Chemistry Diastereomer Biochemistry Combinatorial chemistry Aldehyde chemistry.chemical_compound Aldol reaction chemistry Drug Discovery Stereoselectivity Selectivity
Zdroj:	Tetrahedron. 64:7920-7928
ISSN:	0040-4020
Popis:	N-Boc-12-aza-epothilone analog (azathilone) 1 is a potent inhibitor of human cancer cell growth and represents a structurally new class of natural product-derived microtubule-stabilizing agents. Compound 1 has been prepared employing a convergent strategy that is based on the consecutive assembly of building blocks 3, 4, and 19 into diene 20 and subsequent RCM-mediated macrocycle formation. The aldol reaction between aldehyde 3 and ketone 4 delivered the required 6R,7S diastereoisomer 5 with good selectivity and provided a reliable entry into the stereoselective synthesis of carboxylic acid 12. RCM with diene 20 was highly E-selective, thus giving efficient access to (E)-9,10-dehydro-1 (2). The latter is a key analog in SAR studies with 1.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::3b73111d31f77cfaa42724becc727e54 https://doi.org/10.1016/j.tet.2008.06.017 Zobrazit plný text záznamu Full Text from ScienceDirect