合成路线1

Addition of phenylmagnesium bromide to cyclohexene oxide (XXI) in the presence of CuCl gave trans-2-phenylcyclohexanol (XXII), which was further esterified with chloroacetyl chloride to afford 2-phenylcyclohexyl chloroacetate (XXIII). Enantioselective hydrolysis of the racemic ester (XXIII) by means of Pseudomonas fluorescens lipase provided pure (1R,2S)-2-phenylcyclohexanol (XXIV), which was again esterified with chloroacetyl chloride, yielding the chiral ester (XXVI). Darzen's condensation of chloro ester (XXVI) with anisaldehyde (X) led to the chiral glycidic ester (XXVII). Epoxide ring opening in (XXVII) with 2-aminothiophenol (VII) furnished amino ester (XXVIII). Intermediate thiazepinone (VIII) was then obtained by cyclization of (XXVIII) using p-toluenesulfonic acid in refluxing xylene. Alternatively, amino ester (XXVIII) was first hydrolyzed to amino acid (XXIX), which was subsequently cyclized with p-toluenesulfonic acid as above (11). The final cyclization of amino acid (XXIX) to the intermediate thiazepinone (VIII) has also been carried out in the presence of trichloroacetic acid