Wiley InterScience Backfile Collection 1832-2000
Chemistry and Pharmacology
The Arndt-Eistert homologation of α-amino acids was studied to determine the stereoselectivity in this reaction by chromatographic up-to-date analytical methods. While carba-mate-protected phenylglycine was transformed to the corresponding β-amino acid methyl ester with a stereoselectivity of only 9:1, all other tested amino acid derivatives (Ala, Phe, Ser, Orn, tert-Leu and perhydro-azepine-2-carboxylic acid, suitably protected) were homologated with full retention of configuration (products 9-17). The intermediate diazo ketones 1-8 were purified and characterized by their NMR spectra. When nucleophiles derived from partially protected sugars were present during decomposition of the diazo ketones (derived from amino acids or dipeptides), a strong dependence of the yield (products 21-24) on the degree of steric hindrance of the nucleophilic OH group was observed. Two of the β-amino acids obtained from the homologation reaction were transformed to α-substituted (25-27, 31, 32) and α,α-disubstituted β-amino acid derivatives (28, 29) with excellent selectivities (in most cases, a single diastereoisomer was obtained).
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