BIOTIN 



the same desthio compound as did ^/-allobiotin, namely, <^/-desthioallo- 

 biotin. It was inactive for yeast, whereas ^/-desthiobiotin was half 

 as active as dJ-biotin (page 449). 



One or two of the known racemic pairs must therefore have the 

 rrflws-configuration at the nitrogen atom, as in I, and the other or 

 others the c^s-configuration, as in II, 



O O 



II li 



c c 



H.N H.N H.N H.N 



c c o 



/ \ / \ 



CH2 CH . (CHo)^ . COOH CH2 CH . (CH2), . COOH 



s s 



(I) (11) 



although it had previously been thought that compounds having two 

 five-membered saturated heterocyclic rings fused through adjacent 

 carbon atoms would exist only in the cis form. 



Further investigation ^ showed that the cis-configuration at the 

 nitrogen atom was present in biotin and the ^raws-configuration in 

 allobiotin and ^^^allobiotin ; for, as already noted, biotin on hydro- 

 genolysis with Raney nickel yielded desthiobiotin, whereas the other 

 two isomers yielded desthioallobiotin. Moreover, allobiotin and epi- 

 allobiotin were obtained when the methyl ester of 3-acetamido-4- 

 benzamidotetrahydrothiophene-2-valeric acid was subjected to hydro- 

 genolysis, hydrolysis and treatment with phosgene. 



Formula I therefore represents ^^allobiotin and dl-episllohiotin, 

 whilst formula II represents <^/-biotin. 



Harris et alJ described the synthesis of ^/-biotin, ^/-allobiotin and 

 ^/-e^mllobiotin by the method previously used for the synthesis of 

 biotin (page 414). The two dehydro-esters obtained by reductive 

 acetylation of the oximes were separately reduced with hydrogen in 

 presence of palladium. The product from one was the ^^/-diamido 

 ester, m.p. 152 to 153° C, which is the precursor of ^/-biotin, whilst 

 the other gave the ^/-allodiamido ester, m.p. 172 to 173° C, together 

 with the ^/-^^zallodiamido ester, m.p. 185 to 187° C, the precursors 

 respectively of allobiotin and ^^^j'allobiotin. 



^/-Allobiotin and ^/-^^iallobiotin are configuratively identical with 

 one other about the asymmetric carbon atoms to which the nitrogen 

 atoms are attached. ^/-Biotin had 50 % of the activity of natural 

 biotin, whilst ^/-allobiotin and (^/-^^^allobiotin were essentially inactive 

 towards L. arabinosus (see page 446). 



416 



