A formal synthesis of (+)-lactacystin from 4-hydroxyproline

A formal synthesis of (+)-lactacystin has been completed from trans-4-hydroxyproline, using a diastereoselective enolate acylation reaction as a key step. Diastereoselectivity was seen to vary as a function of the steric bulk of the C4-O-protecting group, and contrary to expectations, the best diast...

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Bibliographic Details
Published in:Tetrahedron letters 2013-01, Vol.54 (1), p.55-57
Main Authors: Mycock, David K., Glossop, Paul A., Lewis, William, Hayes, Christopher J.
Format: Article
Language:English
Subjects:
(+)-Lactacystin
Acylation
Carbonates
Dehydration
Diastereoselective
Enolate acylation
Hydrogenation
Oxidation
Quaternary stereogenic centre
Synthesis (chemistry)
Tetrahedrons
trans-Hydroxyproline
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Summary:A formal synthesis of (+)-lactacystin has been completed from trans-4-hydroxyproline, using a diastereoselective enolate acylation reaction as a key step. Diastereoselectivity was seen to vary as a function of the steric bulk of the C4-O-protecting group, and contrary to expectations, the best diastereoselectivities were obtained when the small methyl carbonate protecting group was used. The formal synthesis was then completed by intercepting Shibasaki’s route via methyl carbonate deprotection, dehydration, 3-pyrroline to 3-pyrrolinone oxidation, hydrogenation and N-CO2Me deprotection.
ISSN:0040-4039
DOI:10.1016/j.tetlet.2012.10.076