合成路线1

The N-protection of 1-aminocyclopentane-1-carboxylic acid (I) with PhCH2-OCOCl and NaOH in tert-butyl methyl ether gives the carbamate (VII), which is condensed with L-tyrosine ethyl ester (VIII) by means isobutyl chloroformate and triethylamine in THF yielding the protected dipeptide (IX). The methylation of (IX) with dimethyl sulfate and K2CO3 in ethyl acetate affords the protected 4-O-methyl dipeptide (X). The deprotection of (X) with HCO2H and Pd/C in ethyl acetate affords the previously reported free dipeptide (V), which is condensed with 2(R)-bromo-3-methylbutyryl chloride (XI) by means of NMM in toluene giving the acylated dipeptide (XII). Finally, this compound is treated with thioacetic acid and K2CO3 in ethyl acetate. The intermediate 2(R)-bromo-3-methylbutyryl chloride (XI) has been obtained by reaction of D-valine (XIII) with NaNO2 and HBr giving the 2(R)-bromo-3-methylbutyric acid (XIV), which is then treated with SOCl2 and DMF to afford the target intermediate (XI).