ENANTIOMERICALLY PURE AMINO-ALCOHOLS AND DIAMINO ALCOHOLS FROM L-ASPARTIC ACID - APPLICATION TO THE SYNTHESIS OF EPISLAFRAMINE AND DIEPISLAFRAMINE

Starting from natural aspartic acid (6) a practical method for the syn thesis of enantiomerically pure 3-amino alcohols 8 including 3,4-diami no derivatives is described. After perbenzylation of 6 and reduction o f both carboxylates, position 4 of the resultant (dibenzylamino)butane diol (11) could be regioselectively blocked to afford the silyloxy-pro tected intermediate 12a. Functionalization of position 1 was accomplis hed by nucleophilic displacement reactions including a 2-fold migratio n of the dibenzylamino substituent or by reductive amination of the am ino aldehyde 15. Both routes proceeded under complete preservation of the optical purity. For envisioned SAR studies, we, furthermore, repor t on the application of this method to a chirospecific synthesis of ep i- and diepislaframine (9a and 9b) as diastereomers of the highly bioa ctive indolizidine alkaloid slaframine (9c). Our first approach includ ing reductive coupling of the chiral amino aldehyde 15 with 5-hydroxyp yrrolidine failed when formation of a quaternary ammonium salt occurre d, preventing the anticipated anionic cyclization. Therefore, we turne d out attention to methodology developed by Wasserman. In fact, introd uction of a 3-hydroxypyrrole-2-carboxylate fragment gave a cyclization precursor (30b) which could be successfully transformed into epi- and diepislaframine.