408 THIAMINE 



NHa-HBr 



/ 

 N=C N CCH3 



CHs-C CCH-Br + H— C C-CHa-CHaOH -^ 



II II \ / 



N— CH S 



NHsHBr 



/ 

 N=C Br 



I I / 

 CH3C C— CH2— N CCH3 



N— CH HC CCH2CH2OH 



S 



chloride by treating with AgCl or by precipitating the practically insol- 

 uble thiamine picrate and disolving it in hydrochloric acid. 



E. SPECIFICITY 



The activity of thiamine seems to be very specific. Even small alterations 

 in the molecule give inactive substances or diminish the activity 100 or 

 1000 times or actually produce antagonistic effects. Most instructive in this 

 respect is the work of Emerson and Southwick.^'* They replaced the methyl 

 group in position 2 in the pyrimidine ring of thiamine by other alkyl groups. 

 Replacement by ethyl does not change the activity, as measured by rat 

 experiments; replacements by propyl gives a definite reduction of the ac- 

 tivity in pigeon tests. When the methyl is changed into an n-butjd group, 

 the activity is reversed. However, Schopfer^^ and Schultz,^® some years 

 before the work of Emerson and South wick, had established that a thiamine 

 having in the second position of the pyrimidine nucleus an ethyl in place 

 of a methyl group has a greater activity than normal thiamine on Phyco- 

 myces and on animals. Their relative activity is expressed by the ratio of 

 ethylthiamine to methylthiamine having the same physiological activity. 

 This ratio for Phycomyces was found to be 0.83:1.0 (Schopfer). The ratio 

 for the pigeon is 0.85:1.0 (Schultz). The discrepancies ■\^^th the results of 

 Emerson and South wick may be due to the inaccuracy of the animal experi- 

 ments. 



Barton and Rogers, in the book of R. J. Williams et al.,^'' give a huge 



1* G. A. Emerson and P. L. Southwick, /. Biol. Chem. 160, 169 (1945). 



1* W. H. Schopfer, Compt. rend. soc. phys. et hist. nat. Genhve pp. 58, 64 (1941). 



15 F. Schultz, Z. physiol. Chem. 265, 113 (1940). 



" A. D. Barton and L. L. Rogers in R. J. Williams, R. E. Eakin, E. Beerstecher, Jr., 

 and William Shive, The Biochemistry of B Vitamins, pp. 684-702. l^einhold Pub- 

 lishing Corp., New York, 1950. 



