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Studies in di- and sesterterpendoid synthesis

University of British Columbia

Stereoselective 9-step conversions of the ketone 17 into the tricyclic ketone 31 via two similar synthetic pathways are described. The highly stereoselective steps involved in the preparation of 31 were: a) the Lewis acid-catalyzed reaction of the silyl enol ethers 50 and 60 with the ethylene ketal of 3-buten-2-one to produce the diketones 37 and 39, respectively, b) the hydrogenation of the enone 32 to give the ketone 56, and c) the Birch reduction of the enone 61 to give 31. Compound 31 contains the correct relative configuration at each of the corresponding chiral centers present in the target molecule 16 and, therefore, appears to be an ideal intermediate for a projected total synthesis of (±)-16 (initially believed to be the sesterterpenoid suvanine). A 15-step total synthesis of the antimicrobial diterpene (±)-8-isocyano-10(14)-amphlilectadiene (23) from the intermediate 24 is described. The key steps in the synthesis of (±)-23 involved the stereoselective Birch reduction of 24, the epimerization of the aldehyde 91 to the corresponding a-formyl isomer, and the degradation of the carboxylic acid function of 95 to an isonitrile group. The last part of the synthetic work described in this thesis resulted in a 15-step conversion of the ketone 17 into the tricyclic ketone 164. Of particular note in this sequence of reactions are: a) the palladium(0)-catalyzed coupling reaction of the enol triflate 143 with lithium cyanide to produce the nitrile 144, b) the stereoselective alkylation of 144 to give compound 148, and c) the stereoselective Birch reduction of the enone 163 to produce 164. The methodology employed in the construction of the tricyclic intermediate 164 contributes to the development of a general route towards the synthesis of the spongiane diterpenes 18-22. [formula omitted]

Text

2011-01-25

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http://hdl.handle.net/2429/30812

Chemistry

University of British Columbia

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