Synthesis of Unit A of Cryptophycin via a [2,3]-Wittig Rearrangement.
The synthesis of unit A of the cryptophycins from (S)-trans-3-penten-2-ol and from (S)-trans-4-hexen-3-ol has been completed. The key stereodetermining step is a [2,3]-Wittig rearrangement of a propargyl ether. Elaboration of the rearrangement product was accomplished by means of a selective hydroboration-oxidation of a terminal alkyne, Horner-Emmons homologation of the derived aldehyde, followed by selective ozonolytic cleavage and Wittig olefination. This synthesis provides easy access to the series of cryptophycin analogues that incorporate a modified aromatic ring in unit A.
Liang
Jian
J
Chemical Process Research and Development, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, and Department of Chemistry, 2545 The Mall, University of Hawaii, Honolulu, Hawaii 96822.
Hoard
David W.
DW
Khau
Vien Van
VV
Martinelli
Michael J.
MJ
Moher
Eric D.
ED
Moore
Richard E.
RE
Tius
Marcus A.
MA