BIOTIN 



permanganate, which does not attack oxybiotin, and then testing the 

 solution with yeast for growth-stimulating activity. They were thus 

 able to show that S. cerevisiae and R. trijolii grown in presence of 

 oxybiotin utilised the compound as such and not after conversion 

 into biotin. Thus the sulphur atom is not essential for biological 

 activity. This conclusion was confirmed by Axelrod et al.^"^ for 5. 

 cerevisiae, by K. K. Krueger and W. H. Peterson ^^a for L. pentosus 

 and by McCoy et al.^^'* for chicks. 



e^j-Oxybiotin was prepared from the second cis-isomer of 3:4- 

 diamino tetrahydr of uran-2 -valeric acid, but neither of the trans- 

 isomers reacted with phosgene, in striking contrast to the corresponding 

 thiophen compounds, all four of which reacted to give cyclic ureides.^^^ 



A series of homologues of oxybiotin, in which the side-chain con- 

 tained two to six methylene groups, were prepared by Hofmann et 

 al.^^ None of the compounds had appreciable biotin activity, and 

 none had any anti-biotin activity at a molar inhibition ratio of 500,000. 

 The nor-(w = 3), homo-(w = 5) and bishomo-(w = 6) analogues had 

 anti-oxybiotin activity, however, at ratios of 143,000, 30,000, and 

 7400 respectively ; the bisnor-(ti = 2) analogue had no activity. 

 With L. arabinosus, only the homo-compound had any activity, a 

 ratio of 225,000. 



Growth Inhibitors 



A number of analogues related to biotin had an inhibitory effect on 

 the growth of certain micro-organisms owing to their ability to compete 

 with biotin for some metabolic process essential for the activity of the 

 cell. Some of these substances functioned as growth promoters under 

 some conditions. 



Biotin sulphone, for instance, although a growth factor for yeast 

 (page 447), inhibited the growth of L. helveticus, L. arabinosus and 

 Staphylococcus aureus,^^ 280 moles of the sulphone antagonising i mole 

 of biotin. ^2 The addition of biotin counteracted the inhibitory effect 

 of the sulphone. 



Another substance that behaved both as a growth inhibitor and 

 as a growth promoter was desthiobiotin (page 410). This had a molar 

 inhibition ratio of 200,000 for S. cerevisiae and of 1,000,000 for L. 

 helveticus}'^' *^ Homodesthiobiotin (page 450) and 5-methyl-2-imid- 

 azolidone had no anti-biotin activity, 2' but two other homologues of 

 desthiobiotin, 2-imidazolidone-4-w-hexoic acid and 5-ethyl-2-imidazoli- 

 done-4-;i-hexoic acid (page 450) antagonised the activity of biotin. 2® 

 a-Isopropyl-5-methyl-2-imidazolidone-4-propionic acid had no anti- 

 biotin activity,^^ whilst the thiourea analogue of desthiobiotin (page 

 449) exhibited only a slight growth inhibitory activity. ^^ 



452 



