The chemical synthesis of amino acyladenylates.

The present paper deals with a description of the method of preparation and partial purification of several amino acid ndcnglates. Two procedures for the synthesis of these compounds have previously been described, but these have certain disadvantages for general application. The first of these m&hods (I) which leads to the synthesis of the leucyl, alanyl, and phcnylalanyl adenylates in yields of about 10 per cent, involved the reaction of the amino acid acyl chloride with the silver salt of adcnosine 5’-phosphate (A5P).i In another method, Wieland et al. (2) used nn-valine thiophenol hydrochloride as the actiratcd amino acid and they were able to cffcct a transfer of the raline moiety to A5P in yields of 10 to 20 per cent. Recently the usefulness of N, N’-diryclohesylcarbodiimide for the synthesis of nuclcoside pyrophosphate derivatives was elegantly demonstrated by Khorana et al. (3-5). Earlier, Zetzche and Fredrich (6) had used the carbodiimidcs for the synthesis of carbosylic acid anhydrides. It seemed, therefore, that the carbodiimides might offer a useful reagent for coupling the amino acids to A5P by an acyl phosphate linkage. Soon after our studies were under way (7) Talbert and Huennekens (8) reported the synt,hesis of butyryl adenylate with DCC. The method to be described here involves the use of DCC to effect a condensation of the carboxyl group of a free amino acid with the phosphate of adenylic acid in aqueous pyridine. Using this procedure the adenylate derivatives of nand n-methionine, L-phenylalanine, L-tryptophan, and L-serine have been prepared and purified.