ANEURINE (thiamine) 



a biological activity of 2-5 fxg. per unit, the activity of the compounds 

 tested ranged from 2-i to 11,800 /tg. per unit. The compounds are 

 listed in the table on page 121, in order of decreasing activity. Com- 

 pounds I to 9 have the general formula : 



N=C . NHj ?« 



I I /C=C . CHa . CHaOH 



II II / Vh-s 



N— CH CI . HCl 



The presence of biological activity in compounds i to 9 indicates 

 that the introduction of additional methylene groups at position 2 

 of the pyrimidine ring and position 4 of the thiazole ring generally 

 reduced, but did not entirely destroy, vitamin B^ activity. The re- 

 moval of the methyl groups from either of these positions was accom- 

 panied by a marked reduction in activity. 



Compound to is of considerable interest, in that the interposition 

 of an additional group between the two rings would at first sight be 

 expected to alter fundamentally the spatial arrangement of the mole- 

 cule, yet some biological activity was apparently retained. The addi- 

 tion of a methyl group to the amino group or an increase in the niunber 

 of carbon atoms in the hydroxyethyl group decreased the activity very 

 considerably, whilst appreciable loss of activity also occurred when 

 the hydroxyethyl group was replaced by a chloroethyl, an ethoxy- 

 ethyl or, according to D. Price and F. D. Pickel,^^ an aminoethyl- 

 group. The introduction of a methyl group into the 6-position of the 

 pyrimidine ring reduced the activity almost to vanishing point, 

 especially if the 2-methyl group was also removed, as in compound 16. 



G. A. Stein et al.^^ found the bromide corresponding to compound 

 16 to be inactive. These workers also prepared the bromide corre- 

 sponding to Schultz's compound i and confirmed that it possessed 

 vitamin B^ activity. In addition, Stein et al. prepared the two 

 compounds : 



N=C . NHj 



Rj.C C.Ra 9^« 



II II /C=C . CHa . CHaOH 

 N— C— CHa— n/ I 



/ X:H— S . HBr 



Br 



where R^ = H and Rg = CH3 in the one instance, and Rj = CH3 and 

 R2 = H in the other, and found them to be inactive. 



F. Schultz,^* reviewing the results previously reported by him, 

 concluded that the activity manifested by certain compounds was 

 not true vitamin Bj activity ; he recalled Fimk's idea that beriberi 

 could be cured either by administering the specific vitanain or by the 



120 



