Application of ring-closing metathesis reactions in the synthesis of epothilones.
There is wide interest in the epothilones, which like the taxoids initiate cytotoxicity through microtubule stabilization. Briefly described is an application of a ring-closing metathesis reaction toward the synthesis of epothilones as carried out in our laboratory. This has led to the discovery of the (E)-9,10-dehydroepothilones as second-generation anticancer drug candidates.
Laboratory for Bioorganic Chemistry, Preclinical Pharmacology Core Facility and Analytical Pharmacology Core Facility, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, New York 10021, USA. s-danishefsky@ski.mskcc.org
Alexey
A
Rivkin
Young Shin
YS
Cho
Ana E
AE
Gabarda
Fumihiko
F
Yoshimura
Samuel J
SJ
Danishefsky
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D034261:Epothilones / Q000138:chemical synthesis* / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D043823:Taxoids
D000970:Antineoplastic Agents; D034261:Epothilones; D043823:Taxoids