II. CHEMISTRY 



535 



CsHij < 



— NH 



\ 

 CO 



/ 



NH 



— COOH 



— C O 



S 

 ^\ 



c o 



Biotin sulfone 



HCl 200° 



CeHia < 



Phosgene 



— NH2 

 — NH2 



—COOH 



I 



— c o 



/^ 



— c o 



Sulfone of the 

 diaminocarboxylic acid 



3. The Side Chain in the Biotin Molecule 



\''aluable information on the structure of biotin was obtained during 

 studies of the oxidative breakdown of the diaminocarboxyhc acid with 

 either alkahne permanganate or with concentrated nitric acid. Such oxi- 

 dation resulted in the formation of adipic acid, C6Hio04.^2' ^' 



HOOC— CH2— CH2— CH2— CH2— COOH 

 Adipic acid 



The isolation of this straight-chain dicarboxylic acid containing six of 

 the carbon atoms of the diaminocarboxylic acid permitted two possible 

 interpretations. The adipic acid might have arisen from an aliphatic side 

 chain in biotin, or from a 6-carbon ring cleaved by oxidation. In the former 

 case the original carboxyl group of biotin would appear as one of the 

 carboxyl groups of adipic acid; in the latter case neither of the carboxyl 

 groups of the adipic acid would be the original carboxyl group in biotin. 

 These two possibilities were put to test by means of a Curtius degradation 

 of biotin methyl ester.^^ In this way the carboxyl group of the diamino- 

 carboxylic acid was replaced by an amino group, as indicated by the follow- 

 ing formulas. 



' — NH f — NH { — NH 



CgHiab 



CO 



/ 



— NH 



^ — COOCH3 

 I 



CsHisS 



CO 



/ 



— NH 



— CONHNH2 

 II 



CsHjsS 



CO 



— NH 



^ —CON, 

 III 



" K. Hofmann, D. B. Melville, and V. du Vigneaud, J . Am. Chem. Soc. 63, 3237 



(1941). 

 " K. Hofmann, D. B. iMelville, and V. du Vigneaud, J. Biol. Chem. 144, 513 (1942). 



