CHEMICAL STRUCTURE AND BIOLOGICAL ACTIVITY 851 



isomer plumbagin (XXII) also has some activity, in spite of the fact that it 

 is impossible to convert it to vitamin Ki. 



^0 OH 



H II I II 



HC C COH HC- \ CH 



H II H 







xxr XM 



There appears to be some activity in the case of three drugs which have 

 the hydroxyl but not the methyl group on 1,4-naphthoquinone. These in- 

 clude lapachol, active at a 5-mg. level, and juglone and lawsone, both of 

 which respond when given at a 10-mg. level. These are massive doses, 

 however, and many of the other compounds inactive at 1-mg. dosage might 

 have shown some effectiveness if tested at these higher levels. 



One of the most markedly depressing effects exerted by the hydroxyl 

 group on antihemorrhagic activity has been noted in the case of 2-methyl-3- 

 (7-hydroxydihydrophytyl)-l,4-naphthoquinone. When 2-methyl-3-i8,7-di- 

 hydrophytyl-l,4-naphthoquinone was fed, it proved to be very active; the 

 curative dose was found to be at a level of only 8 ^g- The simple introduc- 

 tion of a single hydroxyl group on the side chain 3 carbons removed from 

 the naphthoquinone ring thus results in a practically complete loss of vit- 

 amin K effect. It should be noted that in the latter case the hydroxyl 

 group is alcoholic, whereas the depressing effect cited earlier caused by the 

 introduction of an hydroxyl group was noted in cases in which it was 

 phenolic in nature. 



The high potency of 2-methyl-3-carbethoxy-l,4-naphthohydroquinone 

 (25 )ug.) may be a reflection of its ready conversion to the corresponding 

 quinone. Koelsch and Byers^^ have suggested that esters of this type can 

 easily revert to the 2-alkyl-l,4-naphthoquinones by saponification and 

 oxidation. 



(J) Biological Activity of Naphthoquinone Oxides 



The colorless naphthoquinone oxides containing one additional oxygen 

 present in the form of a bridge between carbons 2 and 3 have been prepared 

 in almost quantitative yield from the yellow quinones, by Fieser and co- 

 workers." They are readily susceptible to reduction; under mild reducing 

 action, they are converted to the naphthohydroquinones, 'v\ath the elimina- 

 tion of the oxygen bridge.''^-^^ Presumably, the oxides have a high biologi- 



" C. F. Koelsch and D. J. Byers, /. Am. Chem. Soc, 62, 560-562 (1940). 

 ^ M. Tishler, L. F. Fieser, and N. L. Wendler, J. Am. Chem. Soc, 62, 2866-2871 

 (1940). 



