合成路线1

Alkylation of N-acetyl-D-cysteine (I) with 1-fluoro-5-methyl-2-nitrobenzene (II) gave adduct (III). After hydrolysis of the acetamido group of (III) with aqueous sulfuric acid, the resulting amine (IV) was protected as the benzyl carbamate (V). Reduction of the nitro group of (V) provided amino acid (VI), which was cyclized to the benzothiazepinone (VII) using EDC. Subsequent alkylation of (VII) with ethyl bromoacetate under phase-transfer conditions yielded (VIII) (1). Cleavage of both N-Cbz group and ethyl ester by HBr in AcOH, followed by introduction of the N-Boc group afforded intermediate (X) (2). Optionally, hydrogenolysis of the N-Cbz group of (VIII) provided amino lactam (XI). This was coupled with N-Boc-O-benzylserine (XII) to give amide (XIII). Then, basic hydrolysis of the ethyl ester produced carboxylic acid (XIV).