ON THE PREPARATION OF BETA-AMINO ACIDS FROM ALPHA-AMINO-ACIDS USING THE ARNDT-EISTERT REACTION - SCOPE, LIMITATIONS AND STEREOSELECTIVITY. APPLICATION TO CARBOHYDRATE PEPTIDATION - STEREOSELECTIVE ALPHA-ALKYLATIONS OF SOME BETA-AMINO ACIDS

The Amdt-Eistert homologation of alpha-amino acids was studied to dete rmine the stereoselectivity in this reaction by chromatographic up-to- date analytical methods. While carbamate-protected phenylglycine was t ransformed to the corresponding beta-amino acid methyl ester with a st ereoselectivity of only 9:1, all other tested amino acid derivatives ( Ala, Phe, Ser, Orn, tert-Leu and perhydro-azepine-2-carboxylic acid, s uitably protected) were homologated with full retention of configurati on (products 9-17). The intermediate diazo ketones 1-8 were purified a nd characterized by their NMR spectra. When nucleophiles derived from partially protected sugars were present during decomposition of the di azo ketones (derived from amino acids or dipeptides), a strong depende nce of the yield (products 21-24) on the degree of steric hindrance of the nucleophilic OH group was observed. Two of the beta-amino acids o btained from the homologation reaction were transformed to alpha-subst ituted (25-27, 31, 32) and alpha,alpha-disubstituted beta-amino acid d erivatives (28, 29) with excellent selectivities (in most cases, a sin gle diastereoisomer was obtained).