合成路线1

The condensation of bicyclo[2.2.1]hept-5-ene-2,3endo-dicarboxylic acid anhydride (I) with 2(R)-hydroxy-2-phenylacetic acid benzyl ester (II) by means of BuLi in THF gives the unsaturated hemiester (III), which is reduced with H2 over Pd/C in methanol yielding the saturated hemiester (IV). The trans-esterification of (IV) with NaOMe in refluxing methanol affords (1R,2S,3S,4S)-bicyclo[2.2.1]heptane-2,3-dicarboxylic acid 2-monomethyl ester (V), which by reaction first with ethyl chloroformate and triethylamine and then with ammonia is converted into the amide ester (VI). Hydrolysis of (VI) with KOH gives (1R,2S,3S,4S)-3-carbamoylbicyclo[2.2.1]heptane-2-carboxylic acid (VII), which by degradation with NaOCl and NaOH is converted to the corresponding amino acid (VIII). The acylation of (VIII) with benzenesulfonyl chloride yields (1R,2S,3S,4S)-3-(phenylsulfonamido)bicyclo[2.2.1]heptane-2-carboxylic acid (IX), which is reduced with NaBH4 in dimethoxyethane giving the corresponding methanol (X). The oxidation of (X) with oxalyl chloride in dichloromethane-DMSO affords the aldehyde (XI), which by a Wittig condensation with methoxymethyl triphenylphosphonium chloride and t-BuOK in THF is converted to the ether (XII). The hydrolysis of (XII) with formic acid gives the corresponding aldehyde (XIII), which by a new Wittig condensation with 4-carboxybutyl triphenylphosphonium bromide and t-BuOK in THF gives (+)-[1R,2S(5Z),3S,4S]-7-[3-(phenylsulfonamido)bicyclo[2.2.1]hept-2-yl]-5-heptenoic acid (XIV). Finally, this compound is converted into the corresponding calcium salt with CaCl2 in water.