D. W. WOOLLEY 



yield 3-acetylpyridine gave rise to a substance which caused nicotinic 

 acid deficiency in animals but not in microorganisms. Furthermore, 

 substitution of — CO — CeHs for the — COOH of pantothenic acid gave 

 rise to phenyl pantothenone which caused pantothenic acid deficiency. 

 The introduction of — COCH3 rather than — COCeHg did not yield a 

 compound that produced unequivocal pantothenic acid deficiency, 

 perhaps because a sufficiently negative ketone was not exchanged for 

 the carboxyl. In the cases of nicotinic acid and /?-aminobenzoic acid, 

 the carboxyl is attached to an aromatic type of nucleus, and therefore 

 the related ketone is more acidic than if this nucleus were aliphatic. 

 On the other hand, in pantothenic acid the carboxyl is aliphatic and 

 may require replacement by an aromatic ketone group. 



The second general method for production of inhibitory com- 

 pounds consists of an exchange of one or more atoms in a ring system. 

 Since so many substances of biological importance are ring com- 

 pounds the method is rather inviting and has proved to be quite fruit- 

 ful. The first representative of the series to be studied was pyrithi- 

 amin, in which the group • — CH==CH — replaced the sulfur atom of 

 thiamin. Other examples are: benzimidazole, in which carbon 

 atoms in a benzene ring replace the nitrogen atoms of the structurally 

 related purines; 2,4-diamino-7,8-dimethyl-10-ribityl-5,10-dihydro- 

 phenazine, similarly related to riboflavin; triazolopyrimidines, in 

 which a nitrogen atom replaces a carbon atom of the imidazole ring 

 of the purines; benzoureidovaleric acid, in which a benzene ring 

 replaces the thiophane ring of biotin; o-aminobenzylmethylthia- 

 zolium chloride, in which a benzene nucleus is substituted for the 

 pyrimidine nucleus of thiamin; 3,3'-methylenebis-[4-hydroxy- 

 coumarin], derived from vitamin K by exchange of a carbon for an 

 oxygen atom along with changes in the side chains; and iodinin in 

 which two nitrogen atoms have replaced carbon atoms in the ring 

 system of the related anthra- and naphthoquinones. Here, as with the 

 first general type of structural modification, the method has worked 

 apparently in every case in which it has been tried. It will really be 

 remarkable if this record continues to stand in the face of more varied 

 application. 



The third, or miscellaneous, group of types of structural change 

 is the scrap heap in which all atypical cases must be collected until a 

 general principle can be seen, and rescued from among them. To 



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