On the total synthesis and preliminary biological evaluations of 15(R) and 15(S) aza-dEpoB: a Mitsunobu inversion at C15 in pre-epothilone fragments.
[reaction-see text] The syntheses of two epothilone analogues, 15(S)-aza-12,13-desoxyepothilone B and the epimeric 15(R)-aza-12,13-desoxyepothilone B, are described. A Mitsunobu inversion was utilized for elaboration of pre-epothilone fragments to the corresponding macrolactam. Tubulin binding and cytotoxicity profiles of these analogues are presented.
Stachel
S J
SJ
Laboratories for Bioorganic Chemistryand Biochemical Pharmacology, Sloan-Kettering Institute for Cancer Research, New York, NY 10021, USA.
Chappell
M D
MD
Lee
C B
CB
Danishefsky
S J
SJ
Chou
T C
TC
He
L
L
Horwitz
S B
SB
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D034261:Epothilones; D004852:Epoxy Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014404:Tubulin / Q000378:metabolism; D014407:Tumor Cells, Cultured
C410207:15-aza-12,13-desoxyepothilone B; D000970:Antineoplastic Agents; D001372:Aza Compounds; D034261:Epothilones; D004852:Epoxy Compounds; D007783:Lactones; D013844:Thiazoles; D014404:Tubulin; C114026:desoxyepothilone B; C093788:epothilone B