SYNTHETIC VITAMINS — MAJOR 



283 



Early in the work on the vitamins, it was recognized that there 

 were at least two water-soluble so-called B vitamins, one stable to 

 heat and the other unstable. The latter was designated vitamin Bi, 

 and the other, the heat-stable factor, was termed vitamin B2. Later 

 is was found there were several heat-stable factors, all essential for 

 the growth of the rat. Using this animal in his tests, Kuhn and 

 others showed in 1933 that one of the heat-stable factors, later termed 

 riboflavin, was the same as a widely distributed and previously 

 described 3'ellow pigment in milk, liver, etc. He isolated the pigment 

 from egg wliite and determined its structure. Both Kuhn and Karrer 

 synthesized riboflavin in 1935. Karrer's synthesis is shown in figure 

 9. Other methods have been developed in this country for the synthe- 

 sis of riboflavin. 



NU 



il 



.c 



I 



C2H5O.CO 



C2H5O.CH 



N = C . OH 

 I I 

 H3C.C C.CN 

 ^ II I 



H — CH 



N — C.OH 

 I I 



H3C.C C.CCOC2H5 



NH 

 II 

 H-.CC 

 ^ I 



NHo 



OC.OC2H5 

 * C.COOC2H5 

 C2H5O.CH 



Acetanl- 

 dine 



Q-etnoxy- 

 msthyletie- 

 a-cyai-.o- 

 acstato 



Chlorlnatlon 



Amlnatlon 

 (Dehydration^ 



^Heduction 



N — C.NH2 

 I I 



H3C.C C.CH2HH2 



!l II 



H — CH 



6-amlno-5-ajTilno- 

 ni9thyl-2-methyl- 

 pyrlmldlno 



Acotaml- ethyl ethoxy- 

 dine metiiylene 



malonate 



B.CSSK 



Jl^m"dlthlo- 



K — C.NH2 



I I 



H3C.C C.CH^NTi.CSH 



II 11 

 N — CH 



6-aff.lno-5-chloform- 



tdnldomothyl-2- 



mathylpyrimldlne 



CHsCOCHCLCBSCSlOH 



H3C 



N = C.NH2.HC1 



I I 



C — CH2 — 



11 II 



N — CH 



Cl 



HC — S OH 



f =C.CH2 

 CH3 



Vitamin Bi chloride 

 hydrochlorldo 



FiGUKE 8. — Todd and Bergel synthesis of vitamin Bi. 



Cbeui. Soc. 1937, p. 364.) 



(Todd and Bergel, Journ. 



Medical interest in this vitamin dates from the work of Sebrell and 

 Butler in 1938 who found that it prevented and cured certain fissures 

 in the corners of the mouths of human beings. Two years ago Syden- 

 stricker found that it prevented and cured a certain type of keratitis. 

 Recent examinations with the so-called slit lamp indicate that there 

 may be a very widespread deficiency of riboflavin in the diet in this 

 country. 



In the manufacture of riboflavin the principal difficulty encountered 

 has been the production of the ribose part of the molecule. Of course 

 ribose is a very rare sugar. It has involved much work by night and 

 by day, including Saturdays and Sundays, to find a good manufactur- 



