Chapter IVD 



BIOTIN 



The stimulating effect of small amounts of natural extracts on the 

 growth of yeast was first described in 1901 by Wildiers, 1 who gave the 

 name "bios" to this growth-promoting substance. Bios was subsequently 

 shown to be a group of factors, one of which was isolated from dried 

 Chinese chick egg yolk in 1935 by Kogl, 2 who characterized the compound 

 as the methyl ester, determined its empirical formula and named it 

 "biotin." 3 du Vigneaud and co-workers isolated biotin from liver 4 and 

 from a milk concentrate 5 and completed the proof of structure. 6 The 

 biotin molecule is indicated by the following formula: 



H 2 C CH— CH 2 — CH 2 — CH 2 — CH 2 — COOH 



V 



biotin 



(cis-hexahydr o-2-oxo-l H-thieno [3,4] imidazole-4-valeric acid) 



The synthesis of the vitamin first reported by Harris et at? has since been 

 accomplished in a number of laboratories by different methods. 



Specificity* 



There are four diastereoisomers or eight optically active modifications 

 corresponding to the structure of biotin. All the racemic diastereoisomers, 

 DL-biotin, 7 - 8 DL-epi-biotin, 9 DL-allobiotin 7> 8 and DL-e?w"-allobiotm, 8 



* A naturally-occurring complex of biotin, biocytin, has recently been isolated 

 in crystalline form from yeast extract (Wright, L. D., el al., J. Am. Chem. Soc, 72, 

 1048 (1950). Biocytin, m. p. 230-240° (dec.) is on a molar basis just as active as 

 biotin for Lactobacillus casei but is inactive for Lactobacillus arabinosus. On acid 

 hydrolysis of biocytin, an equivalent of 40= t = 4 per cent of biotin determined micro- 

 biologically is produced. Biocytin also replaces biotin in the nutrition of Lactobacillus 

 delbmckii LD 5 , Lactobacillus acidophilus, Streptococcus faecalis R, Neurospora 

 crassa and Saccharomyces carlsbergensis, but the complex is inactive for Lacto- 

 bacillus pentosus and Leuconostoc mesenteroides P-60 as well as Lactobacillus 

 arabinosus. 



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