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Total Synthesis of (+)‐Lactacystin
Author(s) -
Panek James S.,
Masse Craig E.
Publication year - 1999
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/(sici)1521-3773(19990419)38:8<1093::aid-anie1093>3.0.co;2-u
Subject(s) - synthon , lactacystin , enantioselective synthesis , aldehyde , metabolite , chemistry , stereochemistry , total synthesis , combinatorial chemistry , catalysis , organic chemistry , biochemistry , ubiquitin , gene
A double stereodifferentiating crotylation between aldehyde 1 and silane ( S )‐ 2 to afford homoallylic alcohol 3 is the key diastereoselective step ( anti : syn >30:1) in an efficient asymmetric synthesis of (+)‐lactacystin. This compound is a metabolite isolated from Streptomyces sp . OM‐6519 that exhibits significant neurotrophic activity. An additional important step in the synthesis is a catalytic asymmetric aminohydroxylation used as the key step in the synthesis of the (2 R ,3 S )‐hydroxyleucine synthon.