合成路线1

A synthesis of (+)-(R)-flesinoxan has been described: The nitration of pyrocatechol (I) with nitric acid gives 3-nitrocatechol (II), which is cyclized with epichlorohydrin (III) and acylated with acetic anhydride, yielding 2-(acetoxymethyl)-5-nitro-1,4-benzodioxan (IV). The reduction of (IV) with H2 over Pd/C in ethanol affords the corresponding amine (V), which is cyclized with bis(2-chloroethyl)amine in refluxing chlorobenzene to afford the piperazine (VI). The reaction of (VI) with N-(4-fluorobenzoyl)aziridine (VII) by means of triethylamine in refluxing acetone gives racemic flesinoxan (VIII), which is then submitted to a carefully controlled enzymatic acetylation with Amano P-30 lipase, which acetylates the (R)-isomer selectively. After separation of the nonesterified compound, the acetate is hydrolyzed to give an enriched product, which is submitted to a new enzymatic esterification to improve the optical purity.