Janus All-Cis 2,3,4,5,6-Pentafluorocyclohexyl Building Blocks Applied to Medicinal Chemistry and Bioactives Discovery Chemistry.
Janus All-Cis 2,3,4,5,6-Pentafluorocyclohexyl Building Blocks Applied to Medicinal Chemistry and Bioactives Discovery Chemistry.
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DOI：
10.1002/chem.202102819
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发表时间：
2021-11-17
影响因子：
4.3
通讯作者：
O'Hagan, David
中科院分区：
文献类型：
--
作者：
Clark, Joshua L.;Neyyappadath, Rifahath M.;Yu, Cihang;Slawin, Alexandra M. Z.;Cordes, David B.;O'Hagan, David
异常极性的全顺式 2,3,4,5,6-五氟环己基（Janus 面）基序的单烷基化衍生物是从 2,3,4,5,6-五氟苯乙酸甲酯 15 的芳基氢化开始制备的。该方法在氢化中使用 Zeng 的 Rh(CAAC) 卡宾催化剂 4，遵循 Glorius 开发的方案。通过官能团操作，所得的 Janus 五氟环己基乙酸甲酯 16 转化为相应的醇 18、醛 13、溴化物 29 和叠氮化物 14，其中一些结构单元用于 Ugi 多组分和 Cu 催化的点击反应。 NBoc 保护的五氟芳基苯丙氨酸甲酯 35 也经过芳基氢化，然后脱保护生成 Janus 面 β-五氟环己基丙氨酸氨基酸 15，该氨基酸被纳入新兴一类候选抗病毒化合物的代表成员中。 Log P 测量表明全顺式 2,3,4,5,6-五氟环己基环系统比苯环具有更强的极性。概述中，本文介绍了包含 Janus 环的新构建模块，并展示了它们向生物活性发现计划中通常使用的分子的进展。 Janus全顺2,3,4,5,6-五氟环己基结构单元已被纳入药物化学类型产品中。这些环己烷具有极化面，代表了药物化学的独特主题。该论文介绍了一系列新的可访问的构建模块，这些构建模块可以被精心制作成多种药物类型结构，展示了它们在生物活性发现化学探索中的更广泛用途。
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. Janus all‐cis 2,3,4,5,6‐pentafluorocyclohexyl building blocks have been incorporated into medicinal chemistry type products. These cyclohexanes have polarized faces and represent a unique motif for medicinal chemistry. The paper introduces a range of new accessible building blocks which can be elaborated into a diversity of drug type structures demonstrating their wider utility for exploration in bioactives discovery chemistry.
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影响因子：
2.7
作者：
Bykova T;Al-Maharik N;Slawin AMZ;O'Hagan D
通讯作者：
O'Hagan D
影响因子：
56.9
作者：
Anand, K;Ziebuhr, J;Hilgenfeld, R
通讯作者：
Hilgenfeld, R
DOI：
10.1002/anie.197508011
发表时间：
1975-01-01
期刊：
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION IN ENGLISH
影响因子：
--
作者：
APPEL, R
通讯作者：
APPEL, R
影响因子：
2.2
作者：
Bouchy, A;Rinaldi, D;Rivail, JL
通讯作者：
Rivail, JL
影响因子：
4.3
作者：
Bykova, Tetiana;Al-Maharik, Nawaf;O'Hagan, David
通讯作者：
O'Hagan, David