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Studies toward total syntheses of drimane type antifeedants from thujone

University of British Columbia

This thesis concerns studies directed towards a total synthesis of the drimane type dialdehyde 90 from thujone 42. The naturally occurring drimane dialdehydes have potent antifeedant activity. Development of a versatile synthesis of the drimane type dialdehydes from thujone was the main objective of this research. The decalone 80 was considered an efficient intermediate leading to the drimane dialdehydes. Much work was devoted to develop syntheses of such C7-decalones from thujone 47. The previously known enone 48, obtained in an efficient manner from thujone 42, is subjected to reduction via catalytic or Birch reduction to afford, in quantitative yield, the cis -fused ketone 62. Deoxygenation of the ketone 62 by Wolff-Kishner reduction afforded 22 in excellent yield. Detailed studies had shown that ozone selectively reacted at the activated tertiary carbon of the isopropyl side chain in molecules such as 22. Thus, the tricyclic alkane 22 was converted to the tertiary alcohol 21 by ozonation. The alcohol 22 was then elaborated to the key intermediate 80 via cyclopropane ring opening, free radical rearrangement and ozonation. The stereochemistry of the various products 62, 72, 73 and 80 with respect to the A/B fusion was established through correlation with the absolute structure and stereochemistry of the diketone 66 the latter being one of the ozonation products of ketone 62. Diketone 66 was subjected to X-ray diffraction analysis. The drimane skeleton was then constructed via formylation of 80 to 81 and the latter converted to 82, via reaction with phenylselenyl chloride followed by oxidative elimination of the resultant product. Conjugate addition of cyanide to the unsaturated keto-aldehyde 82 afforded 81. The latter was converted into the unsaturated aldehyde 85 via reduction of its (n-butylthio)methylene derivative, followed by borohydride reduction and mild hydrolysis. Protection of the aldehyde group in 85 gave 86 and the nitrile group in the latter was then reduced to give 88. The latter was then hydrolyzed to the drimane dialdehyde 90. The synthesis of 90 was accomplished in sixteen steps with an overall yield of 4% from thujone 47, thereby indicating that the individual steps in the sequence proceed in excellent yield. The biological activity of compound 90 will be evaluated. Approaches towards a total synthesis of the natural drimane polygodial 1 are also shown. [See Thesis for Diagram]

Text

2010-08-16

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http://hdl.handle.net/2429/27454

Chemistry

University of British Columbia

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