READY ACCESS TO STEREODEFINED GAMMA-HYDROXY-GAMMA-AMINO ACIDS - ENANTIOSELECTIVE SYNTHESIS OF FULLY PROTECTED CYCLOHEXYLSTATINE

A convenient entry to enantiopure syn or anti beta-hydroxy-gamma-amino acids is described. The starting compounds for the synthesis, anti 3- amino-1,2-diols, are readily available in high enantiomeric purity thr ough catalytic asymmetric epoxidation of an allylic alcohol and titani um-promoted oxirane opening. After adequate protection of the nitrogen , a stereodivergent sequence leads to both anti and syn N-Boc-aminoalk yl epoxides. Subsequent regioselective ring-opening with cyanide, prot ection of the resulting secondary alcohol and nitrile to carboxyl conv ersion afford, in good yields, protected beta-hydroxy-gamma-amino acid s belonging to either the anti (erythro) or syn (three) series. This m ethodology has been applied to the enantioselective preparation of cyc lohexylstatine, a key component of several aspartyl protease inhibitor s, in fully protected form. Copyright (C) 1996 Elsevier Science Ltd