558 THE BIOCHEMISTRY OF B VITAMINS 



bishomooxybiotin prevents the utilization of oxybiotin at approximately 

 the same molar ratio at which DL-bishomobiotin prevents the utilization 

 of biotin. However, this does not hold true for inhibitions with homooxy- 

 biotin and homobiotin. The molar ratios determined with the correspond- 

 ing growth factors differ by a factor of ten, and the discrepancy increases 

 to over 100 fold for the next lower homologues of oxybiotin and biotin. 

 In the presence of ammonium sulfate, biotin or oxybiotin stimulates 

 the fermentation rate of biotin-deficient yeast. If either DL-homooxy- 

 biotin or the sulfonic acid corresponding to oxybiotin is added before 



CO CO 



HN NH HN NH 



HC CH HC CH 



H 2 C CH— (CH 2 ) 6 — COOH H,C CH— (CH 2 ) 4 — S0 3 H 



o o 



homooxybiotin hexahydro-2-oxo-l H-furo[8,4]imidazole- 



4~(4~butanesulfonic acid) 

 (oxybiotin sulfonic acid) 



oxybiotin or biotin, the analogues prevent the fermentation at inhibition 

 ratios of 3,750 and 5,000 respectively, for oxybiotin, and 375,000 and 

 600,000 for biotin. If the inhibitors are added after the addition of biotin, 

 no inhibitory effect is observed, indicating that the inhibitors prevent 

 the conversion of biotin to a functional form which is not antagonized by 

 the analogues. The effect of aspartic acid on fermentation is not altered 

 by the inhibitors. 40 



DL-Hexahydro-2-oxo-4- (5-benzylthiopentyl) -lH-furo [3,4] imidazole, 

 DL-hexahydro-2-oxo-4- (4-mercaptobutyl) -lH-furo [3,4] imidazole, and 

 DL-hexahydro-2-oxo-4- (5-mercaptopentyl) -lH-furo [3,4] imidazole are re- 

 ported to have an inhibitory effect on Saccharomyces cerevisiae. 



Ureylenephenyl and Ureylenecyclohexylbutyric and Valeric Acids. A 

 group of 2,3- and 3,4-ureylenephenyl and ureylenecyclohexylbutyric 

 and valeric acids have been synthesized and found to inhibit the utiliza- 

 tion of biotin in a number of organisms. The activities of these compounds 

 against Lactobacillus casei and Saccharomyces cerevisiae are indicated 

 in Table 17. y-(2,3-Ure3^1enecyclohexyl) butyric acid and S-(2,3-urey- 

 lenecyclohexyl) valeric acid are the most effective compounds against 

 yeast, whereas y- (3,4-ureylenecyclohexyl) butyric acid was the most effec- 

 tive against Lactobacillus casei. Two diastereoisomers distinguished by 

 different melting points were obtained in the case of each of the 2,3- 

 ureylenecyclohexyl-derivatives; however, in contrast to other biotin 



