ANEURINE (thiamine) 



in the hydroxyethyl side-chain, and 3-(4'-amino-2'-chloro-6'-methyl- 

 5'-pyrimidyl-methyl) -5-j8-hydroxyethyl-4-methyl - thiazolium chloride 

 had only slight growth-promoting activity, whilst the 2-methyl 

 analogue of aneurine and the compound derived from aneurine by 

 loss of the hydroxyethyl group were inactive. 



The bromide corresponding to the a-hydroxyethyl compound 

 prepared by Knight and Mcllwain was prepared by Baumgarten et al.,^ 

 who found it to have no antineuritic activity. 



Knight and Mcllwain also tested the effect of various pyrimidine 

 derivatives in place of 4-amino-5-aminomethyl-2-methyl-pyrimidine, 

 the thiazole moiety being present in each instance. Substitution of 

 aminomethyl group by the hydroxymethyl or thioformamidomethyl 

 group resulted in active compounds, but all other changes in the 

 molecule resulted in loss of activity. Similarly, the effect of changing 

 the substituents attached to the thiazole ring was studied. Activity 

 was retained when the jS-hydroxyethyl group was replaced by the 

 /3-acetoxyethyl group and, to a less extent, by a p- or y-hydroxy- 

 propyl group. The introduction of an a-hydroxyethyl group into the 

 molecule and most other structural changes resulted in loss of activity. 

 4-Methyl-5-vinyl-thiazole, however, had a slight and delayed activity 

 possibly due to hydration to the hydroxyethyl derivative. 



A micro-organism that can utilise the two halves of the aneurine 

 molecule is the flagellate, Polytomella caeca (see page 112). The effect 

 on the response of this organism of changing the nature of the substit- 

 uent at carbon atom 5 in the pyrimidine moiety was examined by 

 M. Javillier and L. Emerique-Blum.'^ They showed that when the 

 substituent was a hydroxymethyl, formyl, aminomethyl or cyano 

 group, growth was stimulated, whereas the compounds containing a 

 carboxyl, amido or methyl group on carbon atom 5 did not permit 

 growth. It is easy to see how the compounds in the first series could 

 readily be converted into aneurine, and how the compounds in the 

 second group could be converted with great difficulty, if at all. 



A micro-organism that responds to the presence of either com- 

 ponent of the aneurine molecule is Rhizopus suinus. Alcoholic fer- 

 mentation by means of this organism was increased ^ by the addition 

 of 4-amino-5-aminomethyl-2-methyl-pyrimidine or the corresponding 

 5-thioformamidomethyl- or 5-hydroxymethyl-derivatives, but re- 

 duced by the addition of 4-amino-5-aminomethyl-2-ethyl-pyrimidine, 

 4-amino-2 : 5-dimethyl-pyrimidine, 4-hydroxy-2 : 5-dimethyl-pyrimi- 

 dine, 4-amino-5-carbethoxy-2-methyl-pyrimidine, 4-amino-6-hydroxy- 

 2-methyl-pyrimidine or uracil. The structure of the thiazole moiety 

 was less critical, and could be varied within wide limits without ad- 

 versely affecting the fennentation, which was increased in the presence 

 of the following compounds : 5-j3-hydroxyethyl-4-methyl-thiazole, 



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