Dyotropic rearrangement facilitated proximal functionalization and oxidative removal of angular methyl groups: efficient syntheses of 23'-deoxy cephalostatin 1 analogues.
Oxidative functionalization (or removal) of a steroidal C18 methyl group is possible using a previously unknown dyotropic rearrangement of a seven-membered fused C-ring lactone to a 6-ring spiro lactone. Spiroketal equilibration led to the 23-deoxy South analogue of cephalostatin 1 (1) in only 12 steps (23% overall yield) from hecogenin acetate 4, and to strained diene South 1 analogue 30 in 11 steps (28% overall). Total synthesis of 23'-deoxy cephalostatin 1 (3) was accomplished in 16 operations from 4 (9% overall; average 86% yield per operation), and that of 16',17'-dehydro-23'-deoxy cephalostatin 1 (36) in 15 operations from 4 (8% overall; av 84%/op).
Li
Wei
W
Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA.
LaCour
Thomas G
TG
Fuchs
P L
PL
D010084:Oxidation-Reduction; D010619:Phenazines / Q000138:chemical synthesis* / Q000737:chemistry; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013148:Spironolactone / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D013237:Stereoisomerism; D013256:Steroids
D010619:Phenazines; D013141:Spiro Compounds; D013256:Steroids; C454806:cephalostatin I; D013148:Spironolactone