II. CHEMISTRY 543 



designated by Kogl a-biotin and /3-biotin, respectively. jS-Biotin should 

 be identical with the l)iotin isolated by the American workers. However, 

 there are discrepancies in the optical activity reported for the /3-biotin 

 methyl ester by the American workers and by Kogl (+57° and +39° in 

 chlorofomi, respectively). For jS-biotin from liver Kogl and ten Ham'*' 

 suggested the following structure. 



This foiTnula has been ruled out by du Vigneaud and his coworkers as a 

 possible structure for biotin isolated from liver. 



Without going into details of the chemical analysis employed by Kogl 

 and his coworkers,"*-"^^ the following final formula was proposed by them for 

 a-biotin isolated from egg yolk. 



CO 



/ \ 

 NH NH 



I I 



CH CH 



I I 



CH2 CH.CHCH(CH3)2 



\ / 1 



S COOH 



The proof presented by Kogl in favor of this structure is not convincing. 

 In the absence of confirming evidence and especially lacking support by 

 successful synthesis, the question whether a-biotin exists as a separate and 

 well-established isomer of biotin must be left open and should be viewed 

 with justified skepticism. In this connection it is of interest that a sup- 

 posedly pure a-biotin preparation ol)tained from Kogl proved" to possess 

 90 to 90 % of the activity of pure jS-biotin — even of synthetic jS-biotin (with 

 correction for the inactivity of ( — )-biotin — for Lactobacillus casei 7469, 

 L. pentosus 124-2, Saccharomyces cerevisiae Y-30, Clostridium acetohutyli- 

 cum S-9, and Neurospora crassa (1-A wild). It is exceedingly unlikely that 

 for a wide variety of organisms two chemically non-identical forms of biotin 

 should have essentially identic^al biological activity. In the following dis- 

 cussion only biotin with the structure (p. 541) elucidated by du Vigneaud 

 and his coworkers will be considered and the distinction between a and fi 

 forms will not l)e maintained. 



" K. K. Krueger and VV. H. Peterson, /. Biol. Chem. 173, 497 (1948). 



