The enantiospecific synthesis of both antipodes of a-methylaspartic acid from (S)tryptophan is described with the key steps being alkylation of the hexabydropytroloindole 4, oxidative degradation of indoles and, for the preparation of the (R)-isomer, Barton reductive decarboxylation.
The asymmetric synthesis of natural and unnatural non-proteinogenic amino acids is an area of considerable interest at the present time.1 The a-disubstituted amino acids, in particular, ate of interest owing to the increased lipophilicity2 and increased resistance to exo-and endo-peptidases and to chemical hydrolysis3 that they confer on peptides into which they a&included. a-Disubstituted amino acids are also known to stabilise helical domains in peptides and have found extensive use as enzyme inhibitors .5 In this laboratory we have developed an enantiospecific synthesis of a-substituted tryptophan derivatives from (S)-tryptophan. The underlying principle of our method is the alkylation, with clean retention of configuration, of the derived hexahydropyrrolo[2.3blindole 3.6.7 We report here on the extension of this tryptophan based methodology to the preparation of asubstituted aspartic acid derivatives as exemplified by the enantiospecific synthesis of both (R)and (S)-amethylaspartic acids, of interest owing to their ability to competitively inhibit aspartate amino nansferase.* As previously described, the (S)-tryptophan derivative 1 was converted in high yield to its cyclic tautomer (2)a.e by dissolution in 85% phosphoric acid at room temperature. Sulfonylation with benxenesulfonyl