Synthesis and biological activity of novel epothilone aziridines.
[reaction: see text]. A series of 12alpha,13alpha-aziridinyl epothilone derivatives were synthesized in an efficient manner from epothilone A. The final semisynthetic route involves a formal double-inversion of stereochemistry at both the C12 and C13 positions. All aziridine analogues were tested for effects on tubulin binding polymerization and cytotoxicity. The results indicate that the aziridine moiety is a viable isosteric replacement for the epoxide in the case of epothilones.
Regueiro-Ren
A
A
Division of Discovery Chemistry, The Bristol-Myers Squibb Pharmaceutical Research Institute, P.O. Box 4000, Princeton, New Jersey 08543-4000, USA. alicia.regueiroren@bms.com
Borzilleri
R M
RM
Zheng
X
X
Kim
S H
SH
Johnson
J A
JA
Fairchild
C R
CR
Lee
F Y
FY
Long
B H
BH
Vite
G D
GD
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001388:Aziridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000737:chemistry*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D001388:Aziridines; D004852:Epoxy Compounds