Reagent-controlled regiodivergent ring expansions of steroids.

Abstract:

:Ring expansion provides a powerful way of introducing a heteroatom substituent into a carbocyclic framework. However, such reactions are often limited by the tendency of a given substrate to afford only one of the two rearrangement products or fail to achieve high selectivity at all. These limitations are particularly acute when seeking to carry out late-stage functionalization of natural products as starting points in drug discovery. In this work, we present a stereoelectronically controlled ring expansion sequence towards selective and flexible access to complementary ring systems derived from common steroidal substrates. Chemical diversification of the reaction intermediate affords over 100 isomerically pure analogs with spatial and functional diversity. This regiodivergent rearrangement, and the concept of using chiral reagents to affect regiocontrol in chiral natural products, should be broadly applicable to late-stage natural product diversification programs.

journal_name

Nat Commun

journal_title

Nature communications

authors

Charaschanya M,Aubé J

doi

10.1038/s41467-018-03248-2

subject

Has Abstract

pub_date

2018-03-05 00:00:00

pages

934

issue

1

issn

2041-1723

pii

10.1038/s41467-018-03248-2

journal_volume

9

pub_type

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