6005-18-1Relevant academic research and scientific papers
The antagonistic effects of khellactones on platelet-activating factor, histamine, and leukotriene D4
Aida,Kasama,Takeuchi,Tobinaga
, p. 859 - 867 (2007/10/02)
Khellactones of Peucedanum praeruptorum Duun., including praeruptorins A (= Pd-Ia, 2) and B (= Pd-II, 11), had an antagonistic effect specifically on platelet aggregation induced by platelet activating factor (PAF) among various aggregating agents examined, and represent a new class of PAF antagonists. We examined the effects of twenty compounds on PAF-induced platelet aggregation and on histamine- and leukotriene D4 (LTD4)-induced contractions in isolated guinea pig ileum. Compounds 2, (±)-cis-3',4'-diacetylkhellactone (3), (±)-cis-4'-acetyl-3'-crotonoylkhellactone (5), (±)-cis-4'-acetyl-3'-tetrolylkhellactone (6), (±)-cis-4'-acetyl-3'-tigloylkhellactone (7), (±)-cis-4'-acetyl-3'-(2''-methylbutyryl)khellactone (8), (±)-cis-3',4'-ditigloylkhellactone (10), and 11 all strongly inhibited PAF-induced platelet aggregation. (±)-cis-4'-Acetyl-3'-(2''-methyl-2''-dodecenoyl)khellactone (9), (±)-cis-4'-ethyl-3'-tigloylkhellactone (13), (±)-cis-4'-ethyl-3'-[N-(2''-triethylammonio)ethylcarbamoyl]khellacton e iodide (16), (±)-trans-3',4'-diacetylkhellactone (18), (±)-trans-4'-acetyl-3'-crotonoylkhellactone (19), (±)-trans-4'acetyl-3'-valerylkhellactone (20), (±)-trans-4'-acetyl-3'-isovalerylkhellactone (21), and (±)-trans-4'-acetyl-3'-tigloylkhellactone (22) were weakly inhibitory. Most of the compounds exhibited noncompetitive antagonist actions on histamine- and LTD4-induced contractions. The potencies of the antagonistic effects on histamine action were in the order 7 = 22 ≥ 2 = 8 = 10 > 6 = 11 = 13 ≥ 5 > 19 = 9 and those on LTD4 action were in the order 6 = 22 = 2 > 10 = 8 > 7 = 9 = 11 ≥ 13. Thus, compounds with potent PAF-antagonistic activities have the following features: cis isomers of khellactone at the C-3' and C-4' positions are more favorable than trans isomers, and the acyl moiety at the C-3' position of khellactone must be of an appropriate molecular size. In the case of histamine- and LTD4-antagonistic activities, both isomers show similar effects and acyl moieties of appropriate size are required at the C-3' and C-4' positions. These results are of interest in regard to the medicinal uses of Peucedanum species as a herbal drug.
SYNTHESIS OF (+/-)-PRAERUPTORIN A AND RELATED KHELLACTONE DERIVATIVES
Bal-Tembe, Swati,Bhedi, Dilip N.,Souza, Noel J. de,Rupp, Richard Helmut
, p. 1239 - 1249 (2007/10/02)
The first synthesis of the pyranocoumarin natural product, (+/-)-praeruptorin A (= Pd-Ia), is described.A general method for the preparation of various khellactone derivatives is reported.
