Biocatalytic Asymmetric Synthesis of (S)- and (R)-Timolol

Giovanni Tosi; Federica Zironi; Emilia Caselli; Arrigo Forni; Fabio Prati

doi:10.1055/s-2004-822395

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Biocatalytic Asymmetric Synthesis of (S)- and (R)-Timolol

Giovanni Tosi, Federica Zironi, Emilia Caselli, Arrigo Forni, Fabio Prati*
Dipartimento di Chimica, Università di Modena e Reggio Emilia, Via G. Campi 183, 41100 Modena, Italy
Fax: +39(59)373543; e-Mail: prati.fabio@unimore.it;

Abstract

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Abstract

A new biocatalytic route for the synthesis of both enantiomers of Timolol (1) is described. Starting from 3,4-dichloro-1,2,5-thiadiazole (2), (R)- and (S)-Timolol (87% ee) were obtained in 35% and 30% overall yield, respectively. Asymmetric reduction of the intermediate haloketone 5 with baker’s yeast afforded the corresponding halohydrin 6 in the optically active form (87% ee), which gave the R enantiomer (distomer) of Timolol. The S enantiomer (eutomer) was obtained via inversion of configuration of the halohydrin following the Mitsunobu procedure.

Key words

asymmetric synthesis - Mitsunobu reaction - enzymes - reductions - epoxides

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