Total synthesis of TMC-95A and -B via a new reaction leading to Z-enamides. Some preliminary findings as to SAR Journal Article

   

Authors:	Lin, S.; Yang, Z. Q.; Kwok, B. H. B.; Koldobskiy, M.; Crews, C. M.; Danishefsky, S. J.
Article Title:	Total synthesis of TMC-95A and -B via a new reaction leading to Z-enamides. Some preliminary findings as to SAR
Abstract:	A full account of the total syntheses of proteasome inhibitors TMC-95A and -B is provided. A key feature of the syntheses involved installation of a cis-propenylamide moiety by a thermal rearrangement of an α-silylallyl amide. The scope and mechanism of the enamide-forming reaction are discussed. Also provided are some preliminary results from SAR studies. It was found that simplified analogues can retain the full potency of proteasome inhibition.
Keywords:	unclassified drug; animals; proteasome inhibitor; enzyme inhibition; proteasome endopeptidase complex; structure activity relation; structure-activity relationship; magnetic resonance spectroscopy; cattle; piperidines; multienzyme complexes; reaction analysis; chemical reaction; synthesis; synthesis (chemical); peptides, cyclic; erythrocytes; heat treatment; amides; amide; chemical activation; cysteine endopeptidases; thermal effects; article; enamels; porteasome; alpha silylallyl amide; enamide; enamine; propylamine; tmc 95a; tmc 95b
Journal Title:	Journal of the American Chemical Society
Volume:	126
Issue:	20
ISSN:	0002-7863
Publisher:	American Chemical Society
Date Published:	2004-05-26
Start Page:	6347
End Page:	6355
Language:	English
DOI:	10.1021/ja049821k
PROVIDER:	scopus
PMCID:	PMC2507741
PUBMED:	15149232
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-2442659012&partnerID=40&md5=079a2d58210edafc4f406cef66aefc42
Notes:	J. Am. Chem. Soc. -- Cited By (since 1996):79 -- Export Date: 16 June 2014 -- CODEN: JACSA -- Source: Scopus

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