Pergamon Tetrahedron: Asymmetry 9 (1998) 629–646 Totally stereocontrolled synthesis of α,β-diamino acids by addition of Grignard reagents to nitrones derived from L-serine Pedro Merino, * Ana Lanaspa, Francisco L. Merchan and Tomas Tejero Departamento de Química Orgánica, ICMA, Universidad de Zaragoza, E-50009 Aragon, Spain Received 11 December 1997; accepted 30 December 1997 Abstract The asymmetric synthesis of protected (2R,3S)- and (2R,3R)-3-substituted 2,3-α-amino acids is reported. The key step in the synthesis of these compounds is the diastereoselective addition of Grignard reagents to α-amino nitrones derived from L-serine. Total stereocontrol of the addition step is achieved by changing the protecting groups in the starting material. The predominant selectivity in each case can be reasonably interpreted in terms of steric effects of the substituents. © 1998 Elsevier Science Ltd. All rights reserved. 1. Introduction Optically active α,β-diamino acids 1–5 are an important class of compounds due to their presence in a variety of antibiotics and other natural products of importance. 1 In particular, 2,3-diaminopropanoic acid 1 occurs in nature both in its free form and as a constituent of cyclic peptides such as viomycin, capreomycins and tuberactinomycins with antibiotic activity. 2 Similarly, 2,3-diaminobutanoic acids 2a and 3a can be found in a variety of peptide antibiotics such as antrimycins, lavendomycin, amphomycin, aspartocin and glumamycin. 1a,b (2S,3R)-2,3-Diamino-4-phenylbutanoic acid 4b is the non-leucine part of the aminodeoxybestatin, an AP-M inhibitor equipotent to the known bestatin. 3 More recently, 2,3- diamino-3-phenylpropanoic acid 2c has been revealed as an alternative to the side chain of Taxol for improving the water solubility of that anticancer drug. 4 * Corresponding author. E-mail: pmerino@posta.unizar.es 0957-4166/98/$19.00 © 1998 Elsevier Science Ltd. All rights reserved. PII: S0957-4166(98)00004-4