ANALOGUES 



Another route was used by Bourquin et al}^ : 

 CHg . CO . CHNa . COOC2H5 + Br . (CH,)^ . COOC2H5 



KOH 



CH3 . CO . CH . (CH,,)5 . COOC2H5 — - CH3 . CO . CHg . (CH2)5 . COOH 



I 

 COOC2H5 



^'^'•^ '•^\ CH3 . CO . C . (CH,)5 . COOH °' > CH3 . CO . CH . (CH2)5 • COOH 



II I 



N . NH . CeHs NH2 



CO CO 



^^1 / \h _?i_ NH \h 



CH3 . C CH . (CH2)5 . COOH CH3 . CH CH . (CH2)5 . COOH 



^/-Nordesthiobiotin was prepared by an analogous series of reactions. 

 Substantially the same method was used by G. Swain, ^oa except that 

 the amino group was introduced by chlorination with sulphuryl 

 chloride, followed by amination with potassium phthalimide. 



Although ^/-desthiobiotin was active towards Saccharomyces 

 cerevisiae, ^/-nordesthiobiotin was not, nor was ^/-i/f-desthiobiotin, 

 prepared by the action of Raney nickel on dl- ip-^-hiotin. 



According to Rubin et al}^ synthetic ^/-desthiobiotin had half the 

 activity of t^-biotin towards S. cerevisiae, but only o-oi to o-i % of the 

 activity of biotin on rats made biotin-deficient by the addition of 

 egg white or succinylsulphathiazole to the diet. 



That desthiobiotin is converted by certain organisms into biotin 

 was confirmed by L. H, Leonian and V. G. Lilly, ^2 who show^ed that 

 12 yeasts and 4 filamentous fungi grown on desthiobiotin converted 

 it into a substance active for L. arabinosus, L. helveticus, Rhizohium 

 trifoUi 205 and Sordaria fimicola, all of which are unable to utilise 

 desthiobiotin. 5. cerevisiae " old process ", however, when grown in 

 presence of biotin and desthiobiotin, yielded substances with biotin 

 activity for the two Lactobacilli, but not for R. trifolii. 



Desthiobiotin had the same activity as biotin for Neurospora crassa, 

 E. coli and Penicillium notatum, 21464 but was inactive for P. 

 chrysogenum 62078.23 This last organism apparently synthesises 

 desthiobiotin and the addition of pimelic acid increased the amount 

 produced. This gives further support to the view that desthiobiotin 

 is an intermediate in the biosjoithesis of biotin. Desthiobiotin could 

 replace biotin as a growth factor for several Clostridial"^ 



The thiourea analogue of desthiobiotin, 5-methyl-2-thio-imidazo- 

 lidone-4-w-hexoic acid, had a very slight growth-promoting activity 

 towards yeast, and this was completely inhibited by avidin.^^ Towards 

 L. helveticus it showed a low anti-biotin activity in comparison with that 

 of desthiobiotin (page 452). 



29 449 



