ANALOGUES 



Analogues of Biotin 



2-y-Hydroxypropyl-2'-ketoimidazolidino-(4' : 5' : 3 : 4)-thiophene 

 (I) and i//-tetradehydrobiotin ^^ (II) : 



CO CO 



NH 



H NH NH NH 



In 



CH C.(CH2)3.0H CH C. (CHaj^.COOH 



\/ \/ 



S (I) S (II) 



were inactive when tested on 5. cerevisiae and on L. arabinosus or 

 L. helveticus ; neither had anti-biotin activity. Analogues of biotin in 

 which the valeric acid side-chain was replaced by y-phenoxy-, y-ben- 

 zyloxy- and y-hydroxy-n-propyl groups were also without biotin activ- 

 ity for L. arabinosus or S. cerevisiae and without anti-biotin activity.^^ 



Biotin Sulphone 



Oxidation of biotin gave a sulphone (page 407) which stimulated 

 the growth of yeast. Even with large amounts, however, growth did 

 not increase beyond a relatively low maximum, which was only about 

 one-third of that obtained with biotin. ^^ The sulphone had only 

 about o-i % the activity of biotin when the two were compared at a 

 level that produced one-quarter of the maximal growth. Biotin 

 sulphone, like desthiobiotin, has anti-biotin activity (see page 452). 



Degradation Products of Biotin 



The diamino-carboxylic acid, 3 : 4-diamino-tetrahydrothiophene-2- 

 valeric acid, derived from biotin by treatment with alkali (page 407), 

 was found to stimulate the growth of yeast in a biotin-free medium. ^^ 

 It possessed about one-tenth the activity of biotin and its action was 

 not inhibited by avidin. It had 4 to 7 % of the activity of biotin for 

 Lactobacilli.^ Diaminopelargonic acid, which on treatment with 

 phosgene yields desthiobiotin, had one-tenth the activity of desthio- 

 biotin towards yeast. ^* The diamino-tetrahydrothiophene-2-valeric 

 acids corresponding to dl-allo- and ^-^^z-allo-biotin were inactive at 

 levels 100 to 250 times that at which biotin was active.' 



Desthiobiotin 



When biotin was treated with Raney nickel an atom of sulphur is 

 lost, giving desthiobiotin (page 410). This was found to stimulate 

 the growth of yeast, but not of L. helveticus.^* ^^ This diverse effect 

 on the two micro-organisms was shown to be due to the ability of 



447 



