合成路线1

The addition of thiophenol (II) to N-(benzyloxycarbonyl)-L-serine beta-lactone (I) by means of NaH in THF gives N-(benzyloxycarbonyl)-(S-phenyl)-L-cysteine (III), which is treated with isobutyl chloroformate, diazomethane and N-nitro-N-nitrosoguanidine in ethyl acetate/ethyl ether to yield the diazo intermediate (IV). The treatment of (IV) with dry HCl in ethyl ether affords the chloromethyl derivative (V), which is reduced with NaBH4 in THF giving the secondary alcohol (VI). The dehydrochlorination of (VI) with KOH in ethanol yields the corresponding epoxide (VII), which is submitted to ring opening with (3S,4aS,8aS)-N-(tert-butyl)decahydroisoquinoline-3-carboxamide (VIII) in hot isopropanol to afford the condensation product (IX). The deprotection of (IX) with 30% HBr in acetic acid gives compound (X) with a free amino group, which is finally acylated with 3-hydroxy-2-methylbenzoic acid (XI) by means of dicyclohexylcarbodiimide (DCC) and hydroxybenzotriazole (HOBT) in THF. The benzoic acid (XI) has been obtained by the following sequence: The condensation of 3-methoxybenzoyl chloride (XII) with aniline (XIII) gives the corresponding anilide (XIV), which is methylated with butyllithium and methyl iodide in THF yielding 2-methyl-3-methoxybenzanilide (XV). Finally, this compound is treated with 5N HCl and 30% HBr in refluxing acetic acid.