Adipic Acid as an Oxidation Product of the Diamino- Carboxylic Acid Derived from Biotin*

In recent communications we have established the molecular formula as well as the nature of the functional groups of biotin (3-5). We now wish to report experiments which give information regarding the carbon skeleton of this compound. The diaminocarboxylic acid, C9H1802N2S, which we had obtained by the treatment of biotin with Ba(OH)z at 140” served as the starting material. This compound upon oxidation with alkaline potassium permanganate at room temperature was found to yield an ether-soluble acidic oxidation product which crystallized from ether in small prisms and melted at 152-153”. This product was identified as adipic acid by the neutral equivalent, by a mixed melting point, and by the preparation of the diamide and the di-/3-naphthylamide. The quantity of adipic acid that we were able to isolate in pure form from the oxidation products amounted to about 20 per cent of that theoretically possible. Adipic acid was also obtained in a somewhat higher yield by oxidation of the diaminocarboxylic acid with nitric acid. The isolation of the same compound under both these oxidizing conditions minimizes to a great extent the possibility of a rearrangement to an intermediate which could have yielded the adipic acid. Thus the consistent formation of adipic acid as an oxidation product of biotin may be interpreted in one of two possible ways. Either biotin contains an aliphatic side chain which is capable of yielding adipic acid or the latter has its origin in a cyclic structure which is cleaved by the oxidation. In the first case one of the carboxyl groups of the adipic acid must be the carboxyl group originally present in biotin, and it should therefore be possible, by the oxidation of a derivative of the diaminocarboxylic acid in which the carboxyl group has been eliminated, to decide between the two alternatives. After several attempts by other methods the objective was achieved by a Curtius degradation. In this way the carboxyl group was replaced by an amino group. Biotin methyl ester was