534 



BIOTIN 



sulfhydryl groups was negative. Oxidation with cold potassium perman- 

 ganate or with H2O2 (in glacial acetic acid) revealed an uptake of two atoms 

 of oxygen, with the formation of biotin sulfone^*- ^^ with the empirical 

 formula of C10H16O5N2S. 



The formation of a sulfone established the thio ether nature of the sulfur 

 atom, and it was, therefore, concluded that biotin is a monocarboxylic 

 acid containing a cyclic urea structure with the sulfur atom in thio ether 

 linkage. 



In the light of the empirical formula of biotin, in the absence of an ethy- 

 lenic linkage, and with the knowledge of the functional groups, it could 

 be calculated that biotin must contain a bicyclic ring system with the 

 sulfur atom as part of one of the rings. 



Kogl and de Man^^ hydrolyzed biotin sulfone at 200° with concentrated 

 hydrochloric acid and obtained a new compound to which they assigned 

 the structure of an aliphatic 9-carbon diaminocarboxy sulfonic acid. They 

 assumed that during this forced hydrolysis the urea ring is opened, resulting 

 in the formation of the sulfone of the diaminocarboxy lie acid, and in 

 addition one of the carbon-sulfur linkages is ruptured to yield the open- 

 chain sulfonic acid derivative as indicated below. 



CeHu < 



— NH 



CO 



/ 

 -NH 



-CO OH HC1200° 



■^ CeHia 



c o 



s 



^\ 



c o 



Biotin sulfone 



— NH2 

 — NH2 

 — COOH 

 — CH 

 — C— SO3H 



9-Carbon diaminocar- 

 boxysulfonie acid 



Melville, Hofmann, and du Vigneaud'*" have been unable to demonstrate 

 a rupture of sulfur-containing ring after treatment of biotin sulfone with 

 concentrated hydrochloric acid at 200°. In their experiments such treat- 

 ment resulted only in the formation of the sulfone of the diaminocarboxylic 

 acid from which biotin sulfone was resynthesized in high yield by treatment 

 with phosgene. Thus, drastic hydrolysis of biotin sulfone does not affect 

 the sulfur part of the molecule. 



" F. Kogl and T. J. de Man, Ho-pveSeyler's Z. physiol. Chem. 269, 81 (1941). 



