BIOTIN 545 



bium trifolii and Clostridium butylicum}' 20 However, more recent experi- 

 ments 21 on a sample of a-biotin isolated by Kogl indicate that with 

 corrections for impurity of the natural biotin and corrections for the 

 inactivity of ( — ) biotin in DL-/?-biotin, a-biotin possesses 90-96 per cent 

 of the activity of synthetic DL-/?-biotin for Lactobacillus casei 7469, 

 Lactobacillus pentosus 124-2, Saccharomyces cerevisiae Y-30, Clostridium 

 acetobutylicum S-9 and Neurospora crassa 1-A wild. If two such isomeric 

 forms of biotin exist, it is indeed remarkable that for a wide variety of 

 organisms the isomers have essentially identical biological activities. 



Oxybiotin (O-Heterobiotin). The synthesis of DL-hexahydro-2-oxo-lH- 

 furo[3,4]imidazole-4-valeric acid, the biologically active oxygen analogue 

 of biotin, was reported almost simultaneously by Hofmann 22 and by 

 Duschinsky et al. 23 Both O-heterobiotin 23 and oxybiotin 24 have been 

 suggested as trivial names for the analogue which is indicated by the fol- 

 lowing formula: 



CO 

 HN NH 



HC CH 



H 2 C CH— (CH 2 ) 4 — COOH 



V 



oxybiotin (O-heterobiotin) 



Since this analogue might exist in stereoisomeric modifications similar 

 to those of biotin, all four theoretically possible racemic forms of 3,4- 

 diamino-2-tetrahydrofuranvaleric acids were prepared. 25 Attempts to con- 

 vert these to the corresponding hexahydro-2-oxo-lH-furo[3,4]imidazole- 

 4-valeric acids were successful with only two of the four diastereoisomers. 

 Since only the two c{s-3,4-diamino-2-tetrahydrofuranvaleric acids formed 

 bicyclic ureylene derivatives, it appears that the tetrahydrofuran ring 

 is more planar in its configuration than the tetrahydrothiophene ring, 

 which apparently allows the formation of ircms-ureylene derivatives. As 

 in the case of biotin, the spatial arrangement of the side chain with 

 respect to the ureylene group of the two diastereoisomers is still unknown. 



Of the two racemic diastereoisomers of the oxygen analogue of biotin, 

 only one, DL-oxybiotin (which is identical with DL-O-heterobiotin) , 26 

 possesses appreciable biological activity. The other, DL-epi-oxybiotin, 25 

 is reported to have slight activity (0.1 per cent that of oxybiotin) for 

 Lactobacillus arabinosus; however, it is suggested that it is likely that 

 the activity is caused by DL-oxybiotin as a contaminant. The racemic 

 modification of the biologically active form has not as yet been resolved; 



