BIOTIN 543 



have been synthesized. Elucidation of the structure of the four racemic 

 modifications has been accomplished to some extent by the conversion of 

 the biotin stereoisomers to the corresponding desthio derivatives. This 

 conversion is effected by the removal of the sulfur of biotin by reduction 

 with Raney's nickel. 10 The structure of the resulting product, desthiobiotin, 

 allows only two racemic forms, since the asymmetry of carbon atom 2 in 

 biotin is destroyed by the reduction. DL-Biotin and Dh-epi-biotin are 



h 



HN NH 



HC CH 



CH 3 CH 2 — (CH 2 ) 4 — COOH 

 desthiobiotin 



reduced to the same DL-desthiobiotin, 9 while both DL-allobiotin and 

 DL-epi-allobiotin give rise to the same DL-allodesthiobiotin. 11 Thus, 

 biotin and epi-biotin differ by being epimeric at carbon 2 where the side 

 chain is attached. Allobiotin is similarly epimeric with epi-allobiotin. 

 Although the exact configuration of these compounds is unknown, the 

 relationship between the epimeric biotins and epimeric allobiotins has 

 been resolved by the relative ease of hydrolysis of the ureylene groups 

 of allobiotin and epi-allobiotin as compared with biotin. The resulting 

 diamino compounds derived from hydrolysis of the allobiotins are also 

 less easily reconverted by the action of phosgene into the original com- 

 pounds than are epimeric biotins. These results suggest that nitrogens 

 of the ureylene group of the epimeric biotins have a as-configuration, 

 whereas the nitrogens of this group in the epimeric allobiotins have a 

 trans configuration as illustrated below: 



CO 

 / \ 



NH H NH H 



CH(CH 2 ) 4 ( 



H 2 C CH(CH 2 ) 4 COOH H 2 C CH(CH 2 ) 4 COOH 



biotin, ep'\-biotin allobiotin, epi-allobiotin 



Of the four racemic diastereoisomers, all except DL-biotin have been 

 reported to be essentially inactive biologically as indicated in Table 11. 



