1988 Fiscal Year Final Research Report Summary
Syntheses of Terpenoids having a Medium-membered Ring: Synthetic Study on Taxane-typed Compounds
| Project/Area Number |
60571011
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Chemical pharmacy
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| Research Institution | The Institute of Physical and Chemical Research |
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Principal Investigator |
OHTSUKA Yasuo The Institute of Physical and Chemical Research, 有機合成化学研究室, 研究員 (40087523)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUI Mineo The Institute of Physical and Chemical Research, 有機合成化学研究室, 研究員 (70109792)
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| Project Period (FY) |
1985 – 1986
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| Keywords | taxane / eight-membered ketone / medium-membered ring / X-ray crystallography / configuration / 12-membered lactam sulfoxide / intramolecular cyclization / irone |
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| Research Abstract |
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.
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