Esterification of N-(benzyloxycarbonyl)-L-aspartic acid beta-tert-butyl ester (I) by means of diazomethane provided the alpha-methyl ester (II), which was subsequently sulfenylated using (2,4-dinitrophenyl)-(4-methoxybenzyl)disulfide (III) in the presence of n-BuLi to furnish the (2R,3R)-sulfide (IV) as the major isomer. Reduction of the methyl ester group of (IV) with DIBAL, followed by Wittig-Horner reaction of a postulated aldehyde aluminoxyacetal intermediate with neopentyl diethoxyphosphoryl methanesulfonate produced the alpha,beta-unsaturated sulfonate ester (V). Reduction of the double bond of (V) employing [(PPh3)CuH]6 in neutral medium afforded the saturated ester (VI) with only a small epimerization at the C2 position. The tert-butyl ester of (VI) was then deprotected with trifluoroacetic acid yielding the free acid (VII).
The resulting free acid (VII) was coupled with the protected dipeptide (VIII) to give tripeptide (IX). Finally, acidic removal of all protecting groups of (IX) provided the title compound.