570 BIOTIN 



the addition of the biotin precedes that of the inhibitors. This indicates 

 that the inhibition must prevent the conversion of biotin to a functional 

 form which is not antagonized by the analogs."^ 



g. Ureylenephenijl and Ureylenecyclohexylbuiyric and Valeric Acids 



A group of 2,3- and 3 , 4-ureylenecyclohexylbutyric and similar valeric 

 acid analogs as well as ureylenephenyl compounds were synthesized."^ 

 Some of them showed potent antibiotin activity (Table VII). The resem- 



TABLE VII'" 

 Ureylenebenzene and Cyclohexane Derivatives as Inhibitory Biotin Analogs 



Molar inhibition rate 



Analog Lactobacillus casei Saccharomyces cerevisiae 



7-(2,3-Ureylenephenyl)butyric acid 25,000,000 310,000 



7-(2,3-Ureylenecyclohexyl)butyric acid" 12,500,000 1,500 



m.p. 218-220° 



7-(2,3-Ureylenecyclohexyl)butyric acid" 6,250,000 1,500 



m.p. 192-194 



6-(2,3-Ureylenephenyl)vaIeric acid 6,250,000 2,500,000 



5-(2,3-UreyIenecyclohe.xyl)valeric acid," 31,000 3,000 



m.p. 222-226° 



5-(2,3-Ureylenecyclohexyl)valeric acid," 31,000 3,000 



m.p. 183-184° 



7-(3,4-Urey]enephenyl)butyric acid*- 1,500,000 6,250,000 



7-(3,4-Ureienecyclohe.xyl)butyric acid*" 4,000 156,000 



5-(3,4-Ureylenephenyl)valeric acid 750,000 1,560,000 



5-(3,4-Ureylenecyclohe.xyI)valeric acid 31,000 156,000 



" Stereoisomeric modifications distintinguished only by melting point. 

 Inhibits growth of Lactobacillus arabinosus. 



blance of 7-(2,3-ureylenecyclohexyl)butyric acid and 7-(3,4-ureylenecyclo- 

 hexyl)butyric acid to biotin is illustrated by their structure formulas. 



O O 



H2C — CH2 HoC — CH— (CHo)3— COOH 



7-(2,3-Ureylenecyclohexyl)butyric acid 7-(3,4-Ureylenecyclohexyl) butyric 



acid 



"6 J. P. English, 11. C. Clapp, Q. P. Cole, I. F. Halverstadt, J. O. Lampen, and R. O. 

 Roblin, J. Am. Chem. Soc. 67, 295 (1945). 



