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Title: Reagent-controlled regiodivergent ring expansions of steroids

Abstract

Ring expansion provides a powerful way of introducing a heteroatom substituent into a carbocyclic framework. Yet, 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.

Authors:
 [1]; ORCiD logo [2]
  1. Univ. of Kansas, Lawrence, KS (United States)
  2. Univ. of North Carolina, Chapel Hill, NC (United States)
Publication Date:
Research Org.:
Univ. of North Carolina, Chapel Hill, NC (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
OSTI Identifier:
1529315
Grant/Contract Number:  
SC0001011
Resource Type:
Accepted Manuscript
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 9; Journal Issue: 1; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English

Citation Formats

Charaschanya, Manwika, and Aubé, Jeffrey. Reagent-controlled regiodivergent ring expansions of steroids. United States: N. p., 2018. Web. doi:10.1038/s41467-018-03248-2.
Charaschanya, Manwika, & Aubé, Jeffrey. Reagent-controlled regiodivergent ring expansions of steroids. United States. doi:10.1038/s41467-018-03248-2.
Charaschanya, Manwika, and Aubé, Jeffrey. Mon . "Reagent-controlled regiodivergent ring expansions of steroids". United States. doi:10.1038/s41467-018-03248-2. https://www.osti.gov/servlets/purl/1529315.
@article{osti_1529315,
title = {Reagent-controlled regiodivergent ring expansions of steroids},
author = {Charaschanya, Manwika and Aubé, Jeffrey},
abstractNote = {Ring expansion provides a powerful way of introducing a heteroatom substituent into a carbocyclic framework. Yet, 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.},
doi = {10.1038/s41467-018-03248-2},
journal = {Nature Communications},
number = 1,
volume = 9,
place = {United States},
year = {2018},
month = {3}
}

Journal Article:
Free Publicly Available Full Text
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Cited by: 3 works
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