合成路线1

3) The cyclization of the previously described trans-4-(methanesulfonyloxy)-1-(3-pyridylmethyl)-L-prolinemethyl ester (XXI) with NaOH in acetonitrile gives the expected lactone (XXVIII), which by methanolysis with K2CO3 in methanol yields cis-4-hydroxy-1-(3-pyridylmethyl)-L-proline methyl ester (XXIX). The acylation of (XXIX) with 4-nitrophenylsulfonyl chloride (XXX) and triethylamine in dichloromethane affords the corresponding cis-sulfonyloxyproline derivative (XXXI), which is treated with the sodium salt of 4-chlorophenylsulfonamide (XXXII) in DMSO to give trans-4-(4-chlorophenylsulfonamido)-1-(3-pyridylmethyl)-L-proline methyl ester (XXV) already obtained. The reduction of (XXV) with NaBH4 in THF yields the corresponding hydroxymethyl derivative (XXXIII), which is oxidized with SO3/pyridine to the previously described aldehyde (XXVI). 4) The condensation of the previously described cis-4-hydroxyproline derivative (XXIX) with N-(4-chlorophenylsulfonyl)carbamic acid methyl ester (XXXIV) by means of triphenylphosphine and diethyl azodicarboxylate (DEAD) in THF gives (2S,4R)-trans-4-[4-chloro-N-(methoxycarbonyl)phenylsulfonamido]-1-(3-pyridylmethyl)pyrrolidine-2-carboxylic acid methyl ester (XXXV), which is reduced with NaBH4 to the trans-hydroxymethyl derivative (XXXIII), already described.