VITAMIN RESEARCH 



also Grussner et al. (10). An interesting oxygen analogue has been 

 described by Hofmann (17). It has significant biological activity 

 according to Pilgrim, Axelrod, Winnick, and Hofmann (40) ; an oxygen 

 analogue of about the same melting point was also reported as bio- 

 logically active by Duschinsky, Dolan, Flower, and Rubin (4). Sub- 

 sequent studies by Hofmann (18) suggest that rf/-oxybiotin (X\'III) 

 and biotin have identical spatial configurations and differ only in the 

 nature of one of the hetero atoms. 



Biosynthesis of vitamins has received little attention. The 

 pioneering experiments on the synthesis of alkaloids under so-called 

 physiological conditions, as described by Robinson (41), Schopf (42), 

 and Hahn and Schales (14), involved the isolation of the alkaloid 

 synthesized as the criterion of the success of the experiments. Experi- 

 ments on biological precursors and on the biosynthesis of vitamins 

 have involved assays with microorganisms, and the production of 

 vitamin activity as the criterion of success. Once again, the utility 

 of microorganisms in vitamin research may be noted. The following 

 examples may serve to illustrate the trends of such vitamin synthesis 

 research. 



Mueller's studies (36) on the nutritional requirements of certain 

 pathogenic bacteria led to the isolation of pimelic acid (XIX) from 

 cow's urine and the establishment of pimelic acid as a growth accessory 

 for the diphtheria bacillus. Eakin and Eakin (5) recognized that this 

 growth activity of pimelic acid, when considered in conjunction with 

 the tentative structural formulas for biotin, as published by du \'\- 

 gneaud, Hofmann, and Melville (58), might mean that pimelic acid 

 was being utilized as a biological precursor in the synthesis of biotin 

 (XX). They selected Aspergillus niger as a satisfactory mold to test 

 this biosynthesis and obtained data which demonstrated the activity 



H02C(CH2)6C02H 



(XIX) 



NH NH 



I I yeast 



CH CH > 



,,>;„,;, K,,.;ii.,c NH CH 



diphtheria bacillus 

 > 



CH CH 



CH2 CH(CH2)4C02H 



CH3 CH2(CH2)4C02H \s/ 



(XXI) (^^) 



103 



