II. CIIKMISTKY 9 



thetic value, a normal cnrhoii chain he'mg more efrectivc than a hraiifhcil 

 chain.*" Again, increasing (he size of the lii , Rj groups i)ro(luces comiKUuids 

 of enhancetl toxicity and activity, the anesthetic value, however, increasing 

 more rajjicliy than tloes the toxi(t effect. '"'- 



Hansen and Fosdick'^'* have described a sulfur analog of noN'ocaine, 

 "thiocaine":^'^' 6' 



HoN— ^ ^— COSCH2CH2N(C2H6)2 



Tills substance has an activity several times that of procaine, and only 

 one-half the toxicity of cocaine.^* 



Fellows^^ has tested some substituted phenyl p-aminobenzoates. The 

 hydrochloride of 2-(piperidinomethyl)-4 , 6-dimethylphenyl-p-aminoben- 



N-HCl 



H2N— </ \>— COO— </ ^>— CH3 



CH3 



zoate was found to be more active topically than cocaine, without produc- 

 ing as high a toxic reaction as does the natural alkaloid. 



The preparation and pharmacology of many other anesthetic esters of 

 PABA have been described in the chemical and patent literatures,^^-^^- *'• ^- 

 to which the reader is referred for more detailed information on this subject. 



In recent years a number of derivatives of PABA of interest as potential 

 biochemical intermediates have been synthesized. Auhagen^^ has prepared 

 and described the properties of the N-(p-aminobenzoyl) derivatives of 

 D-, L-, and DL-leucine, of D-, L-, and DL-glutamic acid, of L-aspartic acid, 

 of glycine, and of glycylglycine. 



King and Spensley^^ have synthesized the N-(p-aminobenzoyl) deriva- 

 tives of DL-isoglutamine, of DL-glutamine, and of L-glutamine. Lampen and 



61 R. Adams, E. K. Rideal, W. B. Burnett, R. L. Jenkins, and E. E. Dreger, ./. Am. 



Chem. Soc. 48, 1758 (1926). 

 « W. B. Burnett, R. L. Jenkins, C. H. Peet, E. E. Dreger, and R. Adams, ./. Am. 



Chem. Soc. 59, 2248 (1937). 

 " H. L. Hansen and L. S. Fosdick, J. Am. Chem. Soc. 55, 2872 (19.33). 

 " N. F. Albertson and R. O. Clinton, J. Am. Chem. Soc. 67, 1222 (1945). 

 " L. S. Fosdick and H. L. Hansen, ./. Pharmacol. Exptl. Therap. 50, 323 (1934). 

 «6 E. J. Fellows, Proc. Soc. Exptl. Biol. Med. 53, 7 (1943). 

 "E. Auhagen, Z. physiol. Chem. 277, 197 (1943). 

 «« F. E. King and P. C. Spcn.sley, J. Chem. Soc. 3159 (1950). 



