PubAg

Main content area

Total Synthesis of Isomalabaricane Triterpenoids

Author:
Boyko, Yaroslav D., Huck, Christopher J., Sarlah, David
Source:
Journal of the American Chemical Society 2019 v.141 no.36 pp. 14131-14135
ISSN:
1520-5126
Subject:
cross-coupling reactions, cytotoxicity, triterpenoids
Abstract:
The first total syntheses of (±)-rhabdastrellic acid A and (±)-stelletin E, highly cytotoxic isomalabaricane triterpenoids, have been accomplished in a linear sequence of 14 steps from commercial geranylacetone. The exceptionally strained trans-syn-trans-perhydrobenz[e]indene core characteristic of the isomalabaricanes is efficiently accessed in a selective manner through a rapid, complexity-generating sequence. This process features a reductive radical polyene cyclization, an unprecedented oxidative Rautenstrauch cycloisomerization, and umpolung α-substitution of a p-toluenesulfonylhydrazone with in situ reductive transposition. A late-stage cross-coupling in concert with a modular approach to polyunsaturated side chains renders this a general strategy for the synthesis of numerous family members of these synthetically challenging and hitherto inaccessible marine triterpenoids.
Agid:
6656861