合成路线1

Synthesis of dysinosin A: The reaction of the commercially available D-mannitol derivative (XXVII) with NaH and MeI in DMF gives the dimethoxy compound (XXVIII), which is hydrogenated with H2 over Pd/C in EtOH/EtOAc to yield the dimethoxy-D-mannitol (XXIX). The selective silylation of the primary OH groups of (XXIX) with Tbdps-Cl and imidazole affords the bis silyl ether (XXX), which is submitted to an oxidative cleavage of its vicinal diol group by means of Pb(OAc)4 to provide 2(R)-methoxy-3-(Tbdps-O)propanal (XXXI) (3). The oxidation of (XXXI) with NaClO2 gives the corresponding carboxylic acid (XXXII), which is condensed with D-leucine benzyl ester (XXXIII) by means of EDC and HOBt in dichloromethane to yield adduct (XXXIV). The reductive cleavage of the benzyl group of (XXXIV) with H2 over Pd/C in methanol affords the substituted leucine (XXXV), which is condensed with the perhydroindole intermediate (XIII) by means of Bop-Cl and DIEA in acetonitrile to provide the amide (XXXVI). The hydrolysis of the methyl ester group of (XXXVI) with LiOH in THF/MeOH gives the carboxylic acid (XXXVII), which is condensed with the aminoethyl-3-pyrroline intermediate (XXVI) by means of EDC and HOBt in dichloromethane to yield the amide intermediate (XXXVIII). The cleavage of the silyl ether group of (XXXVIII) by means of TBAF in THF affords the primary alcohol (XXXIX), which is treated with Pyr/SO3 and Bu2SnO to provide the sulfate ester (XL). Finally, this compound is fully deprotected by means of TFA in dichloromethane and purified by means of preparative HPLC to obtain the target dysinosin A (2).