合成路线1

1) The cyclization of meso-2,6-bis(benzyloxycarbonylamino)heptanedioic acid (I) with PCl5 gives the corresponding bis oxazolidinedione (II), which is treated with tert-butyl carbazate (III) yielding the bis hydrazide (IV). Enzymatic hydrolysis of (IV) with Streptomyces sapporonensis affords the (S)-monoacid (V), which is selectively protected with benzyl chloroformate and copper chelate (VI). A second protection reaction of (VI) with tert-butoxycarbonyl anhydride gives the amino protected acid (VII) , which is condensed with D-alanine benzyl ester (VIII) by means of isobutyl chloroformate to afford the acylated D-alanine (IX). Elimination of the benzyloxycarbonyl groups of (IX) by hydrogenolysis yields compound (X) with a free amino group, which is condensed with N-heptanoyl-D-glutamic acid 1-benzyl monoester (XI) to give the protected FK-565 precursor (XII). Finally, this compound is deprotected with trifluoroacetic acid and sodium periodate.