合成路线1

The synthesis of the acyl glucuronide of ML-3000 has been described: The cleavage of the lactone ring of D-glucuronic acid gamma-lactone (I) gives the bromide derivative (II), which is treated with silver oxide and benzyl alcohol to yield compound (III). The methanolysis of (III) with sodium methoxide in methanol, followed by treatment with tert-butyldimethylsilyl chloride (TBDMS-Cl) and imidazole affords silylated compound (IV). The hydrolysis of the ester group of (IV) with NaOH in THF/water, followed by reesterification with diethyl chlorophosphate, 2,2,2-trichloroehanol and DMAP gives the silylated trichloroethyl ester (V), which is debenzylated by hydrogenation with H2 over Pd/C in ethyl acetate yielding D-glucuronate (VI). The esterification of the acid group of ML-3000 (VII) with (VI) by means of triphenylphosphine and DIAD in THF affords the corresponding ester (VIII), which is finally deprotected first with Zn and KH2PO4 to eliminate the trichloroethyl group, and then with THF in acetonitrile to eliminate the silyl groups. The product wasisolated as a 1:2 mixture of the alpha- and beta-anomers.