14 タキサン型ジテルペノイドの合成研究(口頭発表の部)  [in Japanese] 14 SYNTHETIC STUDIES ON TAXANE DITERPENES  [in Japanese]

The taxane diterpenes (e.g. taxusin (2), isolated from various species of Taxus, have the unique tricyclic carbon skeleton. Some of them (e.g. taxol (1) are expected to be anticancer agents. Due to the biological importance and unusual structural feature, the synthesis of taxane diterpenes is extensively studied. Herein, we wish to describe the first synthesis of taxane ring system having correct absolute configuration. Our strategy involves the intramolecular Diels-Alder reaction of triene c to form tetracyclic compound b, and the base-induced C-C bond fragmentation reaction of b affording carbon framework of taxanes as the crucial steps (Fig I). The synthesis of taxane ring system 28 was succeeded stereo-selectively as shown in Scheme III. Sequential Michael reaction of kinetic enolate of (+)-carvone with α,β-unsaturated ester 4, prepared from D-mannitol, gave bicyclo[2.2.2]octane derivative 5. The compound 5 was converted into triene 24 via acetal 6, methyl ketone 20 and butenolide 22. Intramolecular Diels-Alder reaction of 24 by heating at 270℃ afforded tetracyclic compound 25 with requisite configuration at C(3) and C(8). Then 25 was transformed into mesylate 26 by two step sequence. The cleavage of C(9)-C(14) bond in 26 was successfully carried out by treatment of 26 with sodium methoxide in methanol to give tricyclo[9.3.1.03,8]pentadecane derivative 27. The optically active 28 having taxane ring system was synthesized by decarboxylation of 27.