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

被引：1

作者：

Dobson, Luca S. ^{[1
]}

Zhang, Qingzhi ^{[1
]}

Mckay, Benjamin A. ^{[1
]}

Oke, Oluwayinka ^{[1
,2
]}

Isanbor, Chukwuemeka ^{[2
]}

Khan, Mohd Faheem ^{[3
]}

Piscelli, Bruno A. ^{[4
]}

Cordes, David B. ^{[1
]}

Cormanich, Rodrigo A. ^{[4
]}

Murphy, Cormac D. ^{[3
]}

O'Hagan, David ^{[1
]}

机构：

[1] Univ St Andrews, Sch Chem, St Andrews KY16 9ST, Fife, Scotland

[2] Univ Lagos, Chem Dept, Lagos 101245, Nigeria

[3] Univ Coll Dublin, Sch Biomol & Biomed Sci, Dublin 4, Ireland

[4] Univ Estadual Campinas, Chem Inst, BR-13083862 Campinas, SP, Brazil

来源：

ORGANIC LETTERS | 2023年 / 25卷 / 37期

基金：

巴西圣保罗研究基金会; 英国工程与自然科学研究理事会;

关键词：

FLUORINATION; METABOLISM;

D O I：

10.1021/acs.orglett.3c02236

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The (ss,ss ',ss ''-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.

引用

页码：6802 / 6807

页数：6

共 43 条

[1] Importance of Physicochemical Properties for the Design of New Pesticides [J].

Akamatsu, Miki .

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 2011, 59 (07) :2909-2917

[2] GFN2-xTB-An Accurate and Broadly Parametrized Self-Consistent Tight-Binding Quantum Chemical Method with Multipole Electrostatics and Density-Dependent Dispersion Contributions [J].

Bannwarth, Christoph ;

Ehlert, Sebastian ;

Grimme, Stefan .

JOURNAL OF CHEMICAL THEORY AND COMPUTATION, 2019, 15 (03) :1652-1671

[3] Metabolically Stable tert-Butyl Replacement [J].

Barnes-Seeman, David ;

Jain, Monish ;

Bell, Leslie ;

Ferreira, Suzie ;

Cohen, Scott ;

Chen, Xiao-Hui ;

Amin, Jakal ;

Snodgrass, Brad ;

Hatsis, Panos .

ACS MEDICINAL CHEMISTRY LETTERS, 2013, 4 (06) :514-516

[4] An overview on the green synthesis and removal methods of pyridaben [J].

Chen, Lingzhu ;

Pan, Mengyuan ;

Hu, Deyu .

FRONTIERS IN CHEMISTRY, 2022, 10

[5] Janus All-Cis 2,3,4,5,6-Pentafluorocyclohexyl Building Blocks Applied to Medicinal Chemistry and Bioactives Discovery Chemistry [J].

Clark, Joshua L. ;

Neyyappadath, Rifahath M. ;

Yu, Cihang ;

Slawin, Alexandra M. Z. ;

Cordes, David B. ;

O'Hagan, David .

CHEMISTRY-A EUROPEAN JOURNAL, 2021, 27 (64) :16000-16005

[6] Ventolin: a market icon [J].

Cova, Bernard .

CONSUMPTION MARKETS & CULTURE, 2022, 25 (02) :195-205

[7] Synthesis and Antifungal Activity of Some 6-tert-butyl-8-chloro-2, 3-dimethylquinolin-4-ol Derivatives against Pyricularia oryae [J].

Fang, Yue-Ming ;

Zhang, Rui-Rui ;

Shen, Zhong-Hua ;

Tan, Cheng-Xia ;

Weng, Jian-Quan ;

Xu, Tian-Ming ;

Liu, Xing-Hai ;

Huang, Hong-Ying ;

Wu, Hong-Ke .

LETTERS IN DRUG DESIGN & DISCOVERY, 2018, 15 (12) :1314-1318

[8] The 25th Anniversary of the Buchwald-Hartwig Amination: Development, Applications, and Outlook [J].

Forero-Cortes, Paola A. ;

Haydl, Alexander M. .

ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2019, 23 (08) :1478-1483

[9] Applications of Fluorine in Medicinal Chemistry [J].

Gillis, Eric P. ;

Eastman, Kyle J. ;

Hill, Matthew D. ;

Donnelly, David J. ;

Meanwell, Nicholas A. .

JOURNAL OF MEDICINAL CHEMISTRY, 2015, 58 (21) :8315-8359

[10] Generation of a set of simple, interpretable ADMET rules of thumb [J].

Gleeson, M. Paul .

JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (04) :817-834

← 1 2 3 4 5 →