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Janus all-cis 2,3,4,5,6-pentafluorocyclohexyl building blocks applied to medicinal chemistry and bioactives discovery chemistry

Research output: Contribution to journalArticlepeer-review

Author(s)

Joshua Clark, Rifahath M. Neyyappadath, Cihang Yu, Alexandra M. Z. Slawin, David B. Cordes, David O'Hagan

School/Research organisations

Abstract

Monoalkylated derivatives of the unusually polar all- cis 2,3,4,5,6- pentafluorocyclohexyl (Janus face) motif are prepared starting from an aryl hydrogenation of 2,3,4,5,6- pentafluorophenylacetate methyl ester 15 . The method used Zeng's Rh(CAAC) carbene catalyst 4 in the hydrogenation following the protocol developed by Glorius. The resultant Janus pentafluorocyclohexylacetate methyl ester 16 was converted to the corresponding alcohol 18 , aldehyde 13 , bromide 29 and azide 14 through functional group manipulations, and some of these building blocks were used in Ugi-multicomponent and Cu-catalysed click reactions. NBoc protected pentafluoroarylphenylalanine methyl ester 35 was also subject to an aryl hydrogenation, and then deprotection to generate the Janus face ß-pentafluorocyclohexyl-alanine amino acid 15 , which was incorporated into representative members of an emerging class of candidate antiviral compounds. Log P measurements demonstrate that the all- cis 2,3,4,5,6-pentafluorocyclohexyl ring system is more polar than a phenyl ring. In overview the paper introduces new building blocks containing this Janus ring and demonstrates their progression to molecules typically used in bioactives discovery programmes.
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Details

Original languageEnglish
Article number202102819
Number of pages7
JournalChemistry - A European Journal
VolumeEarly View
Early online date6 Oct 2021
DOIs
Publication statusE-pub ahead of print - 6 Oct 2021

    Research areas

  • Organofluorine chemistry, Janus motif, Aryl hydrogenation, Organic chemistry, Fluorocyclohexanes

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ID: 275759219

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