SYNTHETIC VITAMINS — MAJOR 285 



In 1933 it. J. Williams discovered an acidic substance which occurred 

 in many natural products that would stimulate the growth of yeast. 

 In the meantime other workers had found that chicks bred under cer- 

 tain special dietary conditions developed a dermatitis which was attrib- 

 uted to the lack of a so-called filtrate factor. In 1939 Elvehjem and 

 Lepkovsky and Jukes found that highly active concentrates of panto- 

 thenic acid would cure this chick dermatitis (pi. 1, fig. 3). Previously 

 Williams had isolated a somewhat crude preparation of pantothenic 

 acid from natural sources. He had shown that pantothenic acid was 

 formed by the combination of j8-alanine with a hydroxy acid. After 



CH2OC2H5 CH20C2H5 CH2OC2H5 



>'° , CH,CN . ^^"SO" . , (j' _HNO. 'Hj' 



C<, * ^"^CN (piperldine) > ch| >0 Ac^O ' CHjll >o 



C"3C=0 / „ H 



PCI5 



CH2OC2H5 CH20C2H5 



isolated as 

 di-picrato 



CH2OC2H5 QHzBr 



Hof^CHaOH H(f^CH2Br 



HONO^... ' "Br ^ r-^- _H20 



->■ c 



"V ^CKjti^/^ Age I 



■r -i 

 Br" 



m.p. 206-208 



mixvd Ri.p. with 



vitamin Be hydrochloride 



HSt 206-208 . 



I00( tingle dot* 



complete cure. 



Figure 10. — Harris and Folkers synthesis of vitamin Bi. (Harris and Folkers, 

 Journ. Amer. Chem. Soc, vol. 61, p. 1245, 1939.) 



the announcement of the probable identity of pantothenic acid with 

 the so-called filtrate factor for chicks the collaboration of our labora- 

 tory was enlisted in the investigation of the structure of this acid. 

 First the hydroxy acid was isolated from natural sources in the form 

 of its lactone. This was shown to be the levo form of a-hydroxy-/3,/3- 

 dimethyl-y-butyrolactone. It was soon synthesized. Pantothenic 

 acid was obtained by combining this lactone with salts of ;S-alanine 

 or its ester followed by hydrolysis. Synthesis of pantothenic acid 

 made it possible to establish without further question the identity of 

 the chick "filtrate factor" with pantothenic acid. 



As was mentioned previously, there has been a growing demand for 

 calcium pantothenate and it is being manufactured in relatively large 

 quantities. 



