Alanine derivatives with reactive groups

The synthesis of diazoketone analogs of amino acids and associated problems were investigated with N-phthaloyl-DL-alanine serving as a model. The carboxyl was activated by conversion to the acid chloride or, under mild conditions, to the mixed anhydride obtained with ethyl chloroformate or dicyclohexylcarbodiimide; the product was reacted with diazomethane. Deblocking the phthaloyl group with hydrazine gave 3-amino-1-diazo-2-butanone as a well-characterized solid salt and as a less stable oil. Further reactions of the blocked diazoketone of DL-alanine, such as conversion to alpha-haloketones, Wolff rearrangement, and deuterium exchange on C-1 were investigated. 3-A-mino-1-diazo-2-butanone had moderate inhibitory activity against mouse mammary adenocarcinoma in cell culture.