合成路线1

Reduction of N-(benzyloxycarbonyl)-4-hydroxyproline (I) with boranedimethylsulfide complex in THF provided the corresponding diol, which was selectively protected at the primary hydroxyl group as the tert-butyldimethylsilyl ether (II). Swern oxidation of the remaining secondary alcohol of (II) afforded ketone (III). This was converted to alkene (IV) by Wittig olefination with methylene triphenylphosphorane. The 1,3-dipolar cycloaddition of (IV) with the nitrile oxide generated from chlorooxime (V) and Et3N furnished spirocycle (VI) as a diastereomeric mixture. Deprotection of the silyl ether of (VI) by treatment with tetrabutylammonium fluoride, followed by Swern oxidation of the resulting alcohol provided aldehyde (VII). Reductive amination of (VII) with 2-aminopyridine (VIII) gave amine (IX), which was protected as the tert-butyl carbamate (X) using Boc2O.