ASYMMETRIC SYNTHESES OF 5-MEMBERED AND 6-MEMBERED CARBOCYCLIC SERINE ANALOGS VIA AN INTRAMOLECULAR STRECKER SYNTHESIS

Conformationally restricted analogs of serine possessing a 5- or 6-mem bered carbocyclic ring, 1 and 2, were synthesized in an optically acti ve form in short steps. The syntheses were started with rac-1, 1-dimet hoxy-2-cyclopentanol and rac-trans-1,2-cyclohexanediol, respectively. The key to the present syntheses was a diastereoselective construction of a chiral amino nitrile group onto the ketone group of 5 or 11. Thi s was achieved by the use of an internal Strecker reaction to give opt ically pure amino nitriles 7a and 13a, respectively. In this reaction, the original chirality derived from phenylalanyl group was efficientl y transplanted into both the ketone and alpha-hydroxyl groups via an i mine-enamine equilibrium of the ketimine intermediate 6 or 12. Phenyla lanyl moiety of the Strecker adducts was removed by oxidative and hydr olytic treatments of the amino nitriles to give the titled amino acids . (C) 1997 Wiley-Liss, Inc.