A Unified Synthetic Approach to
Polyketides Having Both Skeletal and
Stereochemical Diversity
Shiying Shang,Hayato Iwadare,Daniel E. Macks,Lisa M. Ambrosini, and
Derek S. Tan*
Pharmacology Program, Weill Graduate School of Medical Sciences of Cornell
University, Molecular Pharmacology & Chemistry Program, and Tri-Institutional
Research Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue,
Box 422, New York, New York 10021
tand@mskcc.org
Received February 16, 2007
Abstract:
An efficient systematic approach to the diversity-oriented synthesis of polyketides has been developed to provide both skeletal and stereochemical
diversity. Each synthetic intermediate is also a desired polyketide fragment and no protecting group manipulations are required. A first-generation synthesis provides a 74-membered polyketide library comprising six different skeletal classes, each in one to five steps from
propargylic alcohol precursors. A study of epoxyol opening reactions revealed unusual reactivity trends based on epoxide configuration.
