Ready access to stereodefined beta-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 through catalytic asymmetric epoxidation of an allylic alcohol and titanium-promoted oxirane opening. After adequate protection of the nitrogen, a stereodivergent sequence leads to both anti and syn N-Boc-aminoalkyl epoxides. Subsequent regioselective ring-opening with cyanide, protection of the resulting secondary alcohol and nitrile to carboxyl conversion afford, in good yields, protected beta-hydroxy-gamma-amino acids belonging to either the anti (erythro) or syn (three) series. This methodology has been applied to the enantioselective preparation of cyclohexylstatine, a key component of several aspartyl protease inhibitors, in fully protected form. Copyright (C) 1996 Elsevier Science Ltd