合成路线1

The reaction of D-tartaric acid (I) with refluxing acetone and sulfuric acid gives the isopropylidene ketal (II), which is reduced with LiAlH4 to yield 2,3-O-isopropylidene-D-threitol (III). The monosilylation of (III) with Tbdms-Cl and NaH affords the monosilyl ether (IV), which is submitted to a Swern oxidation to provide the aldehyde (V). The reaction of (V) with CBr4, PPh3 and BuLi in dichloromethane gives the acetylene (VI), which is desilylated with TBAF in THF to yield the carbinol (VII). The carbinol (VII) is treated with CBr4 and PPh3 in dichloromethane to afford the bromide (VIII), which is condensed with N-benzyl-N-(trimethylsilyl)amine (IX) by means of K2CO3 in refluxing acetonitrile, providing the tertiary amine (X). The cyclization of (X) by means of ultraviolet light in isopropanol/dichloromethane gives the methylenepiperidine (XI), which is submitted to hydroboration with 9-BBN and NaOH in THF to yield the carbinol (XII) as a single diastereomer. The cleavage of the ketal group of (XII) by treatment with HCl in methanol affords the chiral 1-benzyl-5-(hydroxymethyl)piperidine-3,4-diol (XIII), which is finally debenzylated by means of H2 over Pd(OH)2 in ethanol to furnish the target isofagomine.