Syntheses of Terpenoids having a Medium-membered Ring: Synthetic Study on Taxane-typed Compounds

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The key step involved a novel construction of the eight-membered ring in taxane-typed compounds by a base-induced intramolecular cyclization of 12-membered lactam sulfoxides we developed for the preparation of medium-ring ketones. A cyclohexene moiety corresponding to the A ring was constructed by the Diels-Alder reaction and converted into 12-membered lactam sulfoxide. Intramolecular cyclization of the lactam sulfoxide was proceeded smoothly to give 4,8,11,11-tetramethylbicyclo[5.3.1]undec-8-en-3-one corresponding to the A and B rings. The allyl group introduced stereoselectively at the C-4 position in this ketone was converted into a methoxycarbonylpropyl group and construction of the C ring by reductive coupling with Ti(0) reagent afforded the taxane-typed compound, 8 ,12,15,15-tetramethyltricyclo[9.3.1.0^<3,8>]-pentadec-12-en-4-one, in which the configuration at the C-3 was determined to be (B/C-cis) by X-ray crystallography. MM2 calculation of various taxane-typed compounds suggested that the desired B/C-trans configuration would be obtained by the synthesis of the analogue having a double bond at the C-11,C-12 positions in the same way. Thus, 2,6,6-trimethy1-5-formy1-1-cyclohexenyl-1-carboxylate was synthesized as the starting material through only 3 steps from ethyl acetoacetate. Two conformational isomers of 12-membered lactam sulfides were obtained from the cyclohexene derivative and those structures were confirmed by X-ray crystallography and/or ^1H-NMR. The desired 8-membered ring ketone corresponding to the A and B rings was synthesized from the minor isomer but not from the major one. (+)-and (-)-1,5,5-Trimethyl-4 -hydroxymethyl-6 -benzyloxyethylcyclohexenes, optical active precursors for taxane synthesis, were synthesized and, for determinatiof absolute configuration, converted into (+)- and (-)-irones, naturally occurring perfume, respectively.