Premium
Total Synthesis of (−)‐Salinosporamide A
Author(s) -
Kaiya Yuji,
Hasegawa Junichi,
Momose Takayuki,
Sato Takaaki,
Chida Noritaka
Publication year - 2011
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.201000602
Subject(s) - stereocenter , pyranose , steric effects , stereoselectivity , chemistry , total synthesis , stereochemistry , natural product , lactam , lewis acids and bases , combinatorial chemistry , enantioselective synthesis , organic chemistry , catalysis
A detailed description of our second‐generation total synthesis of salinosporamide A is presented. Three contiguous stereocenters in the γ‐lactam structure seen in the natural product were established by stereoselective functionalization of a D ‐arabinose scaffold, including an Overman rearrangement to generate a highly congested tetrasubstituted carbon center. One of the definitive reactions in the synthesis was a Lewis acid mediated skeletal rearrangement of a pyranose structure, which enabled the practical conversion of the carbohydrate scaffold to the γ‐lactam structure embedded in salinosporamide A. The use of a benzyl ester as a protective group for a sterically hindered carboxylic acid led to a one‐pot global deprotection at the end of the synthesis.