40 II. CHEMISTRY OF FATTY ACIDS AND GLYCEROL 



leprae {Mycobacterium leprae) has rendered possible the determination 

 of the particular linkages responsible for activity. It was first found that 

 the therapeutic action of chaulmoogra oil was due to the cyclic acids pres- 

 gj-^^ 162,177 Homochaulmoogric and homohydnocarpic acids, each of which 

 contains an additional methylene group in the side chain as compared with 

 its parent acid, were both found to be inactive when tested with B. leprae."^ 

 On the other hand, chaulmoogrjdacetic acid prepared by Yan Dyke and 

 Adams''^ had some acti\ity, while a series of synthetic 2-cyclopentenyl-2- 

 alkylacetic acids had an increasing bactericidal effect as the alkyl group 

 was lengthened from the pentyl to the nonyl residue.'^" 



Dean and his collaborators '^^^^^^ reported that the ethyl esters of the 

 chaulmoogra oil fatty acids were also biologically active. Although no 

 relationship was found to exist between unsaturation of non-cyclic acids 

 and growth-inhibiting action toward another acid-fast organism, the tu- 

 bercle bacillus/'^^ the activity of completely hydrogenated chaulmoogra oil 

 was reduced to zero^^^; this would seem to indicate that the cyclopentene 

 nucleus is essential. However, Hasseltine^^^ has reported the successful 

 treatment of human leprosy with dihydrochaulmoogric acid, which would 

 appear to be contradictory. Possibly this may indicate that the conditions 

 inhibiting the growth of Bacillus tuberculosis {Mycobacterium tuberculosis) 

 and of Bacillus leprae, respectively, are not identical. 



Furthermore, the ring structure need not be limited to a 5-carbon one, 

 as cyclohexyl-, cyclobutyl-, and even cyclopropyl-derivatives have anti- 

 bacterial potency. A series of cyclohexyl acids prepared by Hiers and 

 Adams 1^^'^*^ showed activity similar to that of the cyclopentyl acids. 

 Maximum efficacy was noted, however, with the Cie and Cis acids, and the 

 bactericidal potency fell off when a greater or smaller number of carbon 

 atoms was present. Similarly, no activity was noted with the cyclopropyl- 

 methyl alkylacetic acids prepared by Ai\'in and Adams ^^'* until at least 16 

 carbon atoms were present in the molecule; the cyclobutylmethyl alkyl- 



1" O. Schobl, Philippine J. Sci., 23, 533-542 (1923). 

 '8 J. Sacks and R. Adams, J. Am. Chem. Soc, .'-,8, 2395-2399 (1926). 

 '=» R. H. Van Dyke and R. Adams, /. Am. Chem. Soc, 48, 2393-2395 (1926). 

 80 J. A. Arvin and R. Adams, J. Am. Chem. Soc., 40, 2940-2942 (1927). 

 181 H. T. lloUman and A. L. Dean, J. Cutan. Diseases, 37, 367-386 (1919). 

 i«2 A. L. Dean and R. Wrenshall, J. Am. Chem. Soc, 42, 2626-2645 (1920). 

 i»3 J. T. McDonald and A. L. Dean, /. Am. Med. Assoc, 76, 1470-1474 (1921). 

 i»^ O. Schobl, Philippine J. Sci., 25, 12.3-134 (1924). 

 ■« O. Schobl, Philippine J. Sci., 25, 135-150 (1924). 



H. E. Hasseltine, U. S. Pub. Health Service Bull., Xo. 141, 1-11 (1924). 

 18' G. S. Hiers and R. Adams, J. Am. Chem. Soc, 48, 1089-1093 (1926). 



G. S. Hiers and R. Adams, J. Am. Chem. Soc, 48, 2385-2393 (1926). 



J. A. Arvin and R. Adams, J. Am. Chem. Soc, 50, 1983-1985 (1928). 



S. G. Ford and R. Adams, J. Am. Chem. Soc, 52, 1259-1261 (1930). 



R. Adams, W. M. SUuiloy, and II. A. Stearns, J. Am. Chem. Soc, oU, 1475-1478 

 (1928). 



