Stereocontrolled Synthesis of Tetrafluoropentanols: Multivicinal Fluorinated Alkane Units for Drug Discovery

被引：21

作者：

Bentler, Patrick ^{[1
]}

Erdeljac, Nathalie ^{[1
]}

Bussmann, Kathrin ^{[1
]}

Ahlqyist, Marie ^{[2
]}

Knerr, Laurent ^{[3
]}

Bergander, Klaus ^{[1
]}

Daniliuc, Constantin G. ^{[1
]}

Gilmour, Ryan ^{[1
]}

机构：

[1] Westfalische Wilhelms Univ Munster, Organ Chem Inst, Corrensstr 40, D-48149 Munster, Germany

[2] Astrazeneca, BioPharmaceut R&D, Drug Metab & Pharmacokinet, SE-43189 Gothenburg, Sweden

[3] Astrazeneca, BioPharmaceut R&D, Med Chem Res & Early Dev Cardiovasc Renal & Metab, SE-43189 Gothenburg, Sweden

来源：

ORGANIC LETTERS | 2019年 / 21卷 / 19期

关键词：

ORGANOFLUORINE CHEMISTRY; CONFORMATION; DIFLUORINATION;

D O I：

10.1021/acs.orglett.9b02662

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A stereodivergent synthesis of four diastereomeric 2,3,4,5-tetrafluoropentanols is disclosed. X-ray crystallographic analysis reveals conformations that manifest sequential stereoelectronic gauche effects (sigma(C-H/C) -> sigma(C-F)*), thereby generating topological diversity via subtle C(sp(3))-H to C(sp(3))-F exchange. Two representative tetrafluoro arrays have been incorporated into truncated analogues of Gilenya for the management of relapsing remitting multiple sclerosis. These closely similar multivicinal fluoroalkanes have notably different physicochemical profiles and were found to be stable in the presence of human microsomes.

引用

页码：7741 / 7745

页数：5

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