A Short, Stereocontrolled, and Practical Synthesis of α-Methylomuralide, a Potent Inhibitor of Proteasome Function

An efficient and practical synthesis of α-methylomuralide (3), a selective inhibitor of proteasomes, has been developed as outlined in Scheme . Among the advantages of this route of synthesis over previously described approaches are (1) ease of scale-up and (2) high yields (28% overall yield of α-me...

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Bibliographic Details
Published in:Journal of organic chemistry 2003-04, Vol.68 (7), p.2760-2764
Main Authors: Saravanan, P, Corey, E. J
Format: Article
Language:English
Subjects:
Catalysis
Chemistry
Combinatorial Chemistry Techniques
Cysteine Endopeptidases
Exact sciences and technology
Heterocyclic compounds
Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms
Indicators and Reagents
Lactams - chemistry
Lactones - analysis
Lactones - chemical synthesis
Lactones - pharmacology
Molecular Structure
Multienzyme Complexes - antagonists & inhibitors
Organic chemistry
Preparations and properties
Protease Inhibitors - analysis
Protease Inhibitors - chemical synthesis
Protease Inhibitors - pharmacology
Proteasome Endopeptidase Complex
Stereoisomerism
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Summary:An efficient and practical synthesis of α-methylomuralide (3), a selective inhibitor of proteasomes, has been developed as outlined in Scheme . Among the advantages of this route of synthesis over previously described approaches are (1) ease of scale-up and (2) high yields (28% overall yield of α-methylomuralide from 6) and stereocontrol (including high enantiocontrol). The synthesis is well suited to the production of 3 in the quantities needed for material-intensive in vivo investigations.
ISSN:0022-3263
1520-6904
DOI:10.1021/jo0268916