Diversity Oriented Clicking (DOC): Divergent Synthesis of SuFExable Pharmacophores from 2-Substituted-Alkynyl-1-Sulfonyl Fluoride (SASF) Hubs.
SuFEx click chemistry
cycloadditions
diversity oriented clicking
heterocycles
sulfonyl fluorides
Journal
Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543
Informations de publication
Date de publication:
20 07 2020
20 07 2020
Historique:
received:
02
03
2020
pubmed:
18
4
2020
medline:
30
3
2021
entrez:
18
4
2020
Statut:
ppublish
Résumé
Diversity Oriented Clicking (DOC) is a unified click-approach for the modular synthesis of lead-like structures through application of the wide family of click transformations. DOC evolved from the concept of achieving "diversity with ease", by combining classic C-C π-bond click chemistry with recent developments in connective SuFEx-technologies. We showcase 2-Substituted-Alkynyl-1-Sulfonyl Fluorides (SASFs) as a new class of connective hub in concert with a diverse selection of click-cycloaddition processes. Through the selective DOC of SASFs with a range of dipoles and cyclic dienes, we report a diverse click-library of 173 unique functional molecules in minimal synthetic steps. The SuFExable library comprises 10 discrete heterocyclic core structures derived from 1,3- and 1,5-dipoles; while reaction with cyclic dienes yields several three-dimensional bicyclic Diels-Alder adducts. Growing the library to 278 discrete compounds through late-stage modification was made possible through SuFEx click derivatization of the pendant sulfonyl fluoride group in 96 well-plates-demonstrating the versatility of the DOC approach for the rapid synthesis of diverse functional structures. Screening for function against MRSA (USA300) revealed several lead hits with improved activity over methicillin.
Identifiants
pubmed: 32301265
doi: 10.1002/anie.202003219
pmc: PMC7572632
mid: NIHMS1613906
doi:
Substances chimiques
Sulfinic Acids
0
sulfuryl fluoride
64B59K7U6Q
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
12460-12469Subventions
Organisme : NCI NIH HHS
ID : P30 CA045508
Pays : United States
Organisme : NIGMS NIH HHS
ID : P50 GM103368
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM117145
Pays : United States
Organisme : NIAID NIH HHS
ID : U54 AI150472
Pays : United States
Informations de copyright
© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
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