Janus All‐Cis2,3,4,5,6‐Pentafluorocyclohexyl Building Blocks Applied to Medicinal Chemistry and Bioactives Discovery Chemistry
Open Access
- 6 September 2021
- journal article
- research article
- Published by Wiley in Chemistry – A European Journal
- Vol. 27 (64), 16000-16005
- https://doi.org/10.1002/chem.202102819
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 β-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.Funding Information
- Engineering and Physical Sciences Research Council
This publication has 71 references indexed in Scilit:
- Incorporation of Fluorinated Phenylalanine Generates Highly Specific Inhibitor of Proteasome’s Chymotrypsin-like SitesJournal of Medicinal Chemistry, 2010
- Synthesis and Structure of Stereoisomeric Multivicinal HexafluoroalkanesAngewandte Chemie, 2009
- Synthesis and Structure of Stereoisomeric Multivicinal HexafluoroalkanesAngewandte Chemie, 2009
- Current State of the Art in HPLC Methodology for Lipophilicity Assessment of Basic Drugs. A ReviewJournal of Liquid Chromatography & Related Technologies, 2007
- Enantioselective Organocatalytic α-Fluorination of AldehydesJournal of the American Chemical Society, 2005
- Fluorine in Medicinal ChemistryChemBioChem, 2004
- Coronavirus Main Proteinase (3CL pro ) Structure: Basis for Design of Anti-SARS DrugsScience, 2003
- A Stepwise Huisgen Cycloaddition Process: Copper(I)-Catalyzed Regioselective “Ligation” of Azides and Terminal AlkynesAngewandte Chemie, 2002
- Tertiary Phosphane/Tetrachloromethane, a Versatile Reagent for Chlorination, Dehydration, and P-N LinkageAngewandte Chemie, 1975
- Tertiäres Phosphan/Tetrachlormethan, ein vielseitiges Reagens zur Chlorierung, Dehydratisierung und PN-VerknüpfungAngewandte Chemie, 1975