Photomediated ring contraction of saturated heterocycles.


Journal

Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511

Informations de publication

Date de publication:
27 08 2021
Historique:
received: 25 03 2021
accepted: 23 07 2021
pubmed: 14 8 2021
medline: 14 8 2021
entrez: 13 8 2021
Statut: ppublish

Résumé

Saturated heterocycles are found in numerous therapeutics and bioactive natural products and are abundant in many medicinal and agrochemical compound libraries. To access new chemical space and function, many methods for functionalization on the periphery of these structures have been developed. Comparatively fewer methods are known for restructuring their core framework. Herein, we describe a visible light-mediated ring contraction of α-acylated saturated heterocycles. This unconventional transformation is orthogonal to traditional ring contractions, challenging the paradigm for diversification of heterocycles including piperidine, morpholine, thiane, tetrahydropyran, and tetrahydroisoquinoline derivatives. The success of this Norrish type II variant rests on reactivity differences between photoreactive ketone groups in specific chemical environments. This strategy was applied to late-stage remodeling of pharmaceutical derivatives, peptides, and sugars.

Identifiants

pubmed: 34385352
pii: science.abi7183
doi: 10.1126/science.abi7183
pmc: PMC8627180
mid: NIHMS1758490
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1004-1012

Subventions

Organisme : NIGMS NIH HHS
ID : R35 GM130345
Pays : United States

Informations de copyright

Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

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Auteurs

Justin Jurczyk (J)

Department of Chemistry, University of California, Berkeley, CA 94720, USA.

Michaelyn C Lux (MC)

Discovery Chemistry, Merck & Co., Inc., Boston, MA 02115, USA.

Donovon Adpressa (D)

Analytical Research and Development, Merck & Co. Inc., Boston, MA 02115, USA.

Sojung F Kim (SF)

Department of Chemistry, University of California, Berkeley, CA 94720, USA.

Yu-Hong Lam (YH)

Computational and Structural Chemistry, Merck & Co. Inc., Rahway, NJ 07065, USA. yu.hong.lam@merck.com charles.yeung@merck.com rsarpong@berkeley.edu.

Charles S Yeung (CS)

Discovery Chemistry, Merck & Co., Inc., Boston, MA 02115, USA. yu.hong.lam@merck.com charles.yeung@merck.com rsarpong@berkeley.edu.

Richmond Sarpong (R)

Department of Chemistry, University of California, Berkeley, CA 94720, USA. yu.hong.lam@merck.com charles.yeung@merck.com rsarpong@berkeley.edu.

Classifications MeSH