Asymmetric synthesis of a xanthine dehydrogenase inhibitor ( S)-(−)-BOF-4272: Utility of chiral alkoxysulfonium salts

A practical synthetic method for a xanthine dehydrogenase inhibitor, ( S)-(−)-BOF-4272, was established utilizing an asymmetric oxidation of diaryl sulfide BOF-4269. The oxidation of the sulfide with 1-chlorobenzotriazole carried out in the presence of 4-cyanopyridine and chiral 2-phenylcyclohexanol...

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Bibliographic Details
Published in:Tetrahedron: asymmetry 1995-12, Vol.6 (12), p.2991-3000
Main Authors: Matsugi, Masato, Hashimoto, Kinji, Inai, Masatoshi, Fukuda, Norio, Furuta, Takuya, Minamikawa, Jun-ichi, Otsuka, Sei
Format: Article
Language:English
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Summary:A practical synthetic method for a xanthine dehydrogenase inhibitor, ( S)-(−)-BOF-4272, was established utilizing an asymmetric oxidation of diaryl sulfide BOF-4269. The oxidation of the sulfide with 1-chlorobenzotriazole carried out in the presence of 4-cyanopyridine and chiral 2-phenylcyclohexanol gave a high enantiomeric excess (73% ee). The sulfoxides in each enantiomerically pure form could be obtained by treating with alkaline hydrolysis or thermolysis of one the diastereomeric intermediate sulfonium salts (>99% de). Thus the transformation into the sulfoxides occur with virtually perfect inversion (alkaline hydrolysis) or retention (thermolysis). It is therefore possible to obtain the target sulfoxide, ( S)-(−)-BOF-4272, from both the two diastereomeric sulfonium intermediates. Asymmetric synthesis of ( S)-(−)-BOF-4272
ISSN:0957-4166
1362-511X
DOI:10.1016/0957-4166(95)00395-9