Aryl (β,β′,β″-Trifluoro)-tert-butyl: A Candidate Motif for the Discovery of Bioactives

[Image: see text] The (β,β′,β″-trifluoro)-tert-butyl (TFTB) group has received very little attention in the literature. This work presents a direct synthesis of this group and explores its properties. The TFTB group arises when the methyl groups of a tert-butyl moiety are exchanged for fluoromethyl...

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Autores principales: Dobson, Luca S., Zhang, Qingzhi, McKay, Benjamin A., Oke, Oluwayinka, Isanbor, Chukwuemeka, Khan, Mohd Faheem, Piscelli, Bruno A., Cordes, David B., Cormanich, Rodrigo A., Murphy, Cormac D., O’Hagan, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10521027/
https://www.ncbi.nlm.nih.gov/pubmed/37682007
http://dx.doi.org/10.1021/acs.orglett.3c02236
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author Dobson, Luca S.
Zhang, Qingzhi
McKay, Benjamin A.
Oke, Oluwayinka
Isanbor, Chukwuemeka
Khan, Mohd Faheem
Piscelli, Bruno A.
Cordes, David B.
Cormanich, Rodrigo A.
Murphy, Cormac D.
O’Hagan, David
author_facet Dobson, Luca S.
Zhang, Qingzhi
McKay, Benjamin A.
Oke, Oluwayinka
Isanbor, Chukwuemeka
Khan, Mohd Faheem
Piscelli, Bruno A.
Cordes, David B.
Cormanich, Rodrigo A.
Murphy, Cormac D.
O’Hagan, David
author_sort Dobson, Luca S.
collection PubMed
description [Image: see text] The (β,β′,β″-trifluoro)-tert-butyl (TFTB) group has received very little attention in the literature. This work presents a direct synthesis of this group and explores its properties. The TFTB group arises when the methyl groups of a tert-butyl moiety are exchanged for fluoromethyl groups. Sequential fluoromethylations result in a decrease of Log P (increasing hydrophilicity), ultimately by 1.7 Log P units in the TFTB group relative to that of tert-butyl benzene itself. A focus is placed on synthetic transformations, conformational analysis, and metabolism of the TFTB group in the context of presenting a favorable profile as a motif for the discovery of bioactives.
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spelling pubmed-105210272023-09-27 Aryl (β,β′,β″-Trifluoro)-tert-butyl: A Candidate Motif for the Discovery of Bioactives Dobson, Luca S. Zhang, Qingzhi McKay, Benjamin A. Oke, Oluwayinka Isanbor, Chukwuemeka Khan, Mohd Faheem Piscelli, Bruno A. Cordes, David B. Cormanich, Rodrigo A. Murphy, Cormac D. O’Hagan, David Org Lett [Image: see text] The (β,β′,β″-trifluoro)-tert-butyl (TFTB) group has received very little attention in the literature. This work presents a direct synthesis of this group and explores its properties. The TFTB group arises when the methyl groups of a tert-butyl moiety are exchanged for fluoromethyl groups. Sequential fluoromethylations result in a decrease of Log P (increasing hydrophilicity), ultimately by 1.7 Log P units in the TFTB group relative to that of tert-butyl benzene itself. A focus is placed on synthetic transformations, conformational analysis, and metabolism of the TFTB group in the context of presenting a favorable profile as a motif for the discovery of bioactives. American Chemical Society 2023-09-08 /pmc/articles/PMC10521027/ /pubmed/37682007 http://dx.doi.org/10.1021/acs.orglett.3c02236 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Dobson, Luca S.
Zhang, Qingzhi
McKay, Benjamin A.
Oke, Oluwayinka
Isanbor, Chukwuemeka
Khan, Mohd Faheem
Piscelli, Bruno A.
Cordes, David B.
Cormanich, Rodrigo A.
Murphy, Cormac D.
O’Hagan, David
Aryl (β,β′,β″-Trifluoro)-tert-butyl: A Candidate Motif for the Discovery of Bioactives
title Aryl (β,β′,β″-Trifluoro)-tert-butyl: A Candidate Motif for the Discovery of Bioactives
title_full Aryl (β,β′,β″-Trifluoro)-tert-butyl: A Candidate Motif for the Discovery of Bioactives
title_fullStr Aryl (β,β′,β″-Trifluoro)-tert-butyl: A Candidate Motif for the Discovery of Bioactives
title_full_unstemmed Aryl (β,β′,β″-Trifluoro)-tert-butyl: A Candidate Motif for the Discovery of Bioactives
title_short Aryl (β,β′,β″-Trifluoro)-tert-butyl: A Candidate Motif for the Discovery of Bioactives
title_sort aryl (β,β′,β″-trifluoro)-tert-butyl: a candidate motif for the discovery of bioactives
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10521027/
https://www.ncbi.nlm.nih.gov/pubmed/37682007
http://dx.doi.org/10.1021/acs.orglett.3c02236
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