合成路线1

2) The esterification of trans-4-hydroxy-L-proline (XVI) with SOCl2 and methanol gives the methyl ester (XVII), which is condensed with 3-(methanesulfonyloxymethyl)pyridine (XVIII), obtained by treatment of 3-(hydroxymethyl)pyridine (XIX) with methanesulfonyl chloride, by means of triethylamine yielding trans-N-(3-pyridylmethyl)-4-hydroxy-L-proline methyl ester (XX). The treatment of (XX) with methanesulfonyl chloride affords the corresponding mesylate (XXI), which by reaction with LiCl in hot polyethylene glycol gives cis-4-chloro-N-(3-pyridylmethyl)-L-proline methyl ester (XXII). The reaction of (XXII) with sodium azide in DMSO yields the trans-4-azido derivative (XXIII), which is reduced with triphenylphosphine in hot ethyl acetate to the corresponding trans-4-amino compound (XXIV). The treatment of (XXIV) with 4-chlorophenylsulfonyl chloride (VIII) and triethylamine in ethyl acetate affords the sulfonamide (XXV), which is reduced with diisobutylaluminum hydride in toluene/dichloromethane giving (2S,4R)-4-(4-chlorophenylsulfonamido)-1-(3-pyridylmethyl)pyrrolidine-2-carbaldehyde (XXVI). Finally, this compound is submitted to a Wittig condensation with (4-carboxybutyl)triphenylphosphonium chloride (XXVII) and potassium tert-butoxide in THF.