102 



AARON BENDICH 



NH, 



C 



/W 

 HS NH 



Thiourea 



EtO-C^ 





 CH 



C 



/\ 



NaOEt, H* 



HO CH(OEt)j 



Ethyl 7,7-diethoxy- 

 acetoacetate 



OH 



HS^N' 



XHO 



2-Thiouracil- 

 4-aldehyde 



OH 



OH 



N 



HO'^N^CHa 

 XVIII 



NaOH 



K,Fe(CN), 



N 



A 



HO N 



COOH 



XXXI 



Orotic acid 



H 



I 

 N-C=0 



^N-C=CHCOOH 

 I 

 H 



KOH 



.NH2 EtO-C=0 

 NH2 = C-CH,COOEt 



HOAc, 



HCl 



0=C: 



H 



I 



,N- 



■C=0 



Urea 



Oxalacetic ethyl ester 



^N-C=CHCOOEt 

 I 

 H 



XXXII 



deavor. Examples shall be cited here of the contributions made by these 

 workers which have strongly influenced modern medicine. Mention has 

 already been made, for instance, of uric acid and gout. Brugnatelli^ ob- 

 tained alloxan (2 , 6-dihydroxypryimidine-4 , 5-dione) in 1818 from the 

 nitric acid oxidation of uric acid. The Wohler and Liebig preparation of 

 alloxan"* is well known. In 1943, the important discovery was made^^^ 

 that the administration of alloxan to rabbits leads to a necrosis of the 

 insulin-producing units of the pancreas (the beta-cells of the islets of 

 Langerhans), thereby providing a tool for the production and study of 

 experimental diabetes. Alloxan is diabetogenic in many animals including 



"6 J. S. Dunn, H. L. Sheehen, and N. G. B. McLetchie, Lancet i, 484 (1943). 



