Synthetic Transformations of Sesquiterpene Lactones. 8*. Synthesis of 13-(2-Oxofuro- [2,3-d]pyrimidin-3(2H)-yl)eudesmanolides

An aza-Michael reaction of isoalantolactone with 5-bromo- or 5-iodo-substituted uracils gave (11R)-13[5-bromo(iodo)-2,4-dioxotetrahydropyrimidin-1-yl]eudesma-4(15)-en-8ȕ ,12-olides, which were highly active in Pd-catalyzed cross-coupling reaction with terminal alkynes. Copper-catalyzed Mannich reaction of (11R)-13-(5-ethynyl-2,4-dioxotetrahydropyrimidin-1-yl)eudesma-4(15)-en-8ȕ ,12-olide with secondary amines and formaldehyde was used for the synthesis of (11R)-13-[5-(diethylamino)propynyl]-, (11R)-13-[5-(pyrrolidinyl-1-yl)propynyl]-, (11R)-13-[5-(4-oxopiperidin-1-yl)propynyl]-, (11R)-13-[5-(4-methylpiperazin-1-yl)propynyl]-, and (11R)-13-(5-{[2-(pyridin-3-yl)piperidin1-yl]propynyl}-2,4-dioxotetrahydropyrimidin-1-yl)eudesmanolides. The treatment of 13-[5(propargylamino)tetrahydropyrimidin-1-yl]eudesmanolides with silver nitrate led to the corresponding (11R)-13(2-oxofuro[2,3-d]pyrimidin-3(2H)-yl)eudesmanolides. The structures of two compounds were proved by X-ray structural analysis.