VITAMIN B (Br) 33 



Williams (1916) published the results of unsuccessful attempts 

 at the isolation of the vitamin from rice polishings by various modifi- 

 cations of Funk's original method. He obtained a very slight yield 

 of crystals melting at 233° C. which were curative in doses of 10 to 

 20 milligrams. An amorphous material also gradually separated which 

 was curative in doses of 20 to 30 miUigrams and proved effective in 

 treating cases of human beriberi. After exhausting every resource to 

 avoid mixed deposits from the final liquor and to increase the yield 

 of needles melting at 233° C. he abandoned the hope of isolating large 

 quantities of an individual vitamin from rice polishings and decided 

 to attempt the synthesis of curative substances, which might throw 

 light on the nature of the vitamin. The facts adduced by Funk and 

 others seemed to Williams to point to the pyridine ring as the most 

 promising nucleus. The most important facts in favor of this choice 

 were the occurrence of nicotinic acid with the vitamin in several 

 natural substances and the stability of the vitamin on heating with 

 sulfuric acid. Nicotinic acid, trigonelline, and /?-oxy-nicotinic acid 

 given by mouth to polyneuritic fowls caused little improvement, but 

 some prolongation of life. The hydrochloride of the methyl ester of 

 nicotinic acid brought about marked, but temporary, improvement. 



Later in the same year Williams (1916a) published the results 

 of experiments upon the antineuritic properties of some synthetic 

 hydroxypyridines. These were selected on account of the fact that 

 antineuritic concentrates when treated with phosphotungstic acid and 

 alkali had given the blue color produced by substances containing 

 hydroxy groups in the benzene ring. 



Polyneuritic pigeons were given doses of from 10 to 100 milli- 

 grams by intramuscular injections. In some cases similar doses were 

 administered by mouth as a supplementary test. The substances tested 

 included nicotinic, cinchomeric, quinolinic, 6-hydroxynicotinic and 

 citrazinic acids, a-hydroxypyridine, glutazine, 2,4,6-trihydroxypyridine 

 and its anhydride, and finally 2,3,4-trihydroxypyridine and the so- 

 called tetrahydroxypyridine. 



Only a-hydroxypyridine, 2,4,6-trihydroxypyridine, and 2,3,4-trihy- 

 droxypyridine were found to have curative power. Moreover, these 

 compounds were curative only when freshly prepared and invariably 

 lost their curative properties on standing. As there was no evidence 

 of decomposition it seemed probable that the change was due to 

 isomerization. A study of the isomeric forms and curative properties 

 of a-hydroxypyridine showed that of the two crystalline forms one 

 exhibited activity and the other did not. Similar results were obtained 



