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An Efficient Synthesis of Lactacystin β‐Lactone
Author(s) -
Donohoe Timothy J.,
Sintim Herman O.,
Sisangia Leena,
Harling John D.
Publication year - 2004
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.200453843
Subject(s) - lactacystin , stereoselectivity , aldol reaction , pyrrole , lactone , chemistry , yield (engineering) , selectivity , stereochemistry , combinatorial chemistry , proteasome , organic chemistry , proteasome inhibitor , biochemistry , catalysis , materials science , metallurgy
A key step in the synthesis of lactacystin β‐lactone ( 3 ), an inhibitor of the 20 S proteasome, was the ammonia‐free reductive aldol reaction of pyrrole 1 to form 2 with complete anti selectivity. This route to 3 takes just 13 steps (14 % overall yield) and allows the late‐stage stereoselective introduction of a methyl group at C4, which is crucial for the production of analogues. Boc= tert ‐butoxycarbonyl.
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