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Conformational Analysis of Acyclic ?-Fluoro Sulfur Motifs.

ABSTRACT: Bioactive small molecules containing ?-fluoro sulfur motifs [RS(O)_n CH₂ F] are appearing with increasing frequency in the pharmaceutical and agrochemical sectors. Prominent examples include the anti-asthma drug Flovent^® and the phenylpyrazole insecticide pyrafluprole. Given the popularity of these structural units in bioactive small molecule design, together with the varying oxidation states of sulfur, a conformational analysis of ?-fluoro sulfides, sulfoxides, and sulfones, would be instructive in order to delineate the non-covalent interactions that manifest themselves in structure. A combined crystallographic and computational analysis demonstrates the importance of hyperconjugative donor-acceptor interactions in achieving acyclic conformational control. The conformational disparity in the syn- and anti-diastereoisomers of ?-fluorosulfoxides is particularly noteworthy.

SUBMITTER: Erdeljac N

PROVIDER: S-EPMC7702044 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Conformational Analysis of Acyclic α-Fluoro Sulfur Motifs.

Erdeljac Nathalie N Mück-Lichtenfeld Christian C Daniliuc Constantin G CG Gilmour Ryan R

Chemistry (Weinheim an der Bergstrasse, Germany) 20200928 60

Bioactive small molecules containing α-fluoro sulfur motifs [RS(O)n CH2 F] are appearing with increasing frequency in the pharmaceutical and agrochemical sectors. Prominent examples include the anti-asthma drug Flovent® and the phenylpyrazole insecticide pyrafluprole. Given the popularity of these structural units in bioactive small molecule design, together with the varying oxidation states of sulfur, a conformational analysis of α-fluoro sulfides, sulfoxides, a ...[more]

PMID: 32735052

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