合成路线1

The bicyclic amino acid building blocks (VI) and (XIV) can be obtained as follows. Reduction of N-Cbz-4-oxoperhydrocyclopenta[c]pyrrole-1-carboxylate (XXI) with NaBH4 in EtOH affords the hydroxy derivative (XXII), which is converted to xanthate (XXIII) by treatment with carbon disulfide, iodomethane and NaH in THF. Desulfurization of (XXIII) by means of tributyltin hydride and AIBN in hot toluene affords the N-protected bicyclic amino ester (XXIV), which is finally submitted to hydrogenolysis over Pearlman’s catalyst to furnish the intermediate (VI) (1). Alternatively, protection of 3-azabicyclo[3.3.0]nonane (XXV) as the N-Boc derivative (XXVI) followed by carboxylation with sec-butyllithium and CO2 gas in the presence of 3,7-dipropyl-3,7-diazabicyclo[3.3.1]nonane leads to the N-protected amino acid (XXVII). After resolution of (XXVII) with either 1,2,3,4-tetrahydro-1(S)-naphthylamine or with (R)-α-methylbenzylamine, the desired 1(S)-amino acid is esterified to (XXVIII) utilizing Boc2O and DMAP in t-BuOH/MTBE. Then, selective Boc group cleavage by means of methanesulfonic acid in THF provides the target intermediate (XIV) (3). Scheme 3.