340 CHEMISTRY OF THE LEUCOMAINS. 



Only one tri-methyl xanthin is possible and that derivative is the 

 active principle of tea and coffee — caffein. 



If the tautomeric formula of xanthin, with the imido group trans- 

 ferred from position 7 to 9, is considered it will be seen that additional 

 derivatives of xanthin are possible, such as a 9-methyl xanthin, 1-9 and 

 3-9 di-methyl xanthins and a 1.3.9-tri-methyl xanthin. The lat- 

 ter is an isomer of caffein but unlike the latter possesses but little 

 action upon the muscle (Schmiedeberg, Berichte, 34, 2556). 



In 1881 Fischer showed that caffein possessed the formula given 

 below. In the following year he succeeded in changing xanthin into 

 theobromin which in turn can be easily methylated to caffein. In 

 1897 Fischer successfully synthesized all of the natural xanthins 

 except 1 -methyl xanthin. The origin of the di-methyl and mono- 

 methyl xanthins was not understood until but recently. Unlike 

 xanthin, these derivatives when found in the urine cannot be traced to 

 tissue metabolism, but on the contrary they result by the splitting 

 off of one or more methyl groups from the caffein or theobromin 

 which is ingested. Thus, when very large doses of caffein are given 

 to a dog all three methyl groups are attacked at once. The one in 

 position 7 is the least firm and hence disappears quite readily. Het- 

 eroxanthin or 7-methyl xanthin is therefore present in minimal 

 amounts and for the same reason theophyllin or 1-3 di-methyl xan- 

 thin is found in larger amounts than paraxanthin or theobromin. It 

 is of singular interest to note that caffein in the body yields not 

 only paraxanthin but also theophyllin and theobromin which 

 have been known heretofore to exist only in the vegetable kingdom. 

 The purin bases which result from the cleavage of caffein in the 

 body vary according to the animal used. Thus, while feeding caf- 

 fein to a dog yields chiefly theophyllin (1-3) and 3-methyl xanthin, 

 in a rabbit it yields chiefly paraxanthin (1-7), 1-methyl xanthin and 

 heteroxauthin (7). 



CH3.N-C 



OC 0— N.CH3 



r 



Caffbiit. 



Guanin. — The fact that guanin is readily changed into xanthin 

 shows that the two bases are closely rfelated. Indeed, the relation is 

 the same as that between adenin and hypoxanthin. By decomposi- 

 tion with concentrated hydrochloric acid Wulff obtained the same 

 products as are given by xanthin. On oxidation, however, with 

 chlorin neither Strecker nor Fischer were able to obtain alloxan 

 and urea, but instead obtained parabanic acid, guanidin, and car- 

 bonic acid. A guanidin residue is contained in the molecule in 

 place of the urea residue in xanthin. A striking difference between 



