Preparation of ( R)- and ( S)-6-hydroxybuspirone by enzymatic resolution or hydroxylation

6-Hydroxybuspirone is an active metabolite of the antianxiety drug buspirone. The ( R)- and ( S)-enantiomers of 6-hydroxybuspirone were prepared using an enzymatic resolution process. l-Amino acid acylase from Aspergillus melleus (Amano Acylase 30000) was used to hydrolyze racemic 6-acetoxybuspirone...

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Published inTetrahedron: asymmetry Vol. 16; no. 16; pp. 2711 - 2716
Main Authors Hanson, Ronald L., Parker, William L., Brzozowski, David B., Tully, Thomas P., Liu, Mark, Kotnis, Atul, Patel, Ramesh N.
Format Journal Article
LanguageEnglish
Published Elsevier Ltd 22.08.2005
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Summary:6-Hydroxybuspirone is an active metabolite of the antianxiety drug buspirone. The ( R)- and ( S)-enantiomers of 6-hydroxybuspirone were prepared using an enzymatic resolution process. l-Amino acid acylase from Aspergillus melleus (Amano Acylase 30000) was used to hydrolyze racemic 6-acetoxybuspirone to ( S)-6-hydroxybuspirone in 95% ee after 45% conversion. The remaining ( R)-6-acetoxybuspirone with 88% ee was converted to ( R)-6-hydroxybuspirone by acid hydrolysis. The ee of both enantiomers could be improved to 99% by crystallization as a metastable polymorph. ( S)-6-Hydroxybuspirone was also obtained in 88% ee and 14.5% yield by hydroxylation of buspirone using Streptomyces antibioticus ATCC 14890.
ISSN:0957-4166
1362-511X
DOI:10.1016/j.tetasy.2005.07.020