Treatment of cedar leaf oil with aqueous potassium permanganate resulted in the oxidative ring opening of thujone (XXIV) to yield the crystalline α-thujaketonic acid (XXV).⁷⁰ This material, because of its availability and interesting structure, represented an attractive starting material for the synthesis of analogues of insect juvenile hormone. Therefore, to achieve this aim, α-thujaketonic acid (XXV) was converted to form two products (or 'half-molecules') which were then coupled together and transformed to the analogues.
In the initial study Grignard treatment of (XXV) produced an intermediate tertiary alcohol (LVIII) which cyclized spontaneously to a lactone (XXVI). The latter compound resisted further transformation and this approach was abandoned.
On the other hand, (XXV) was refluxed in water to give β-thujaketonic acid (XXIX). This ring-opened acid was hydrogenated to give the ketoacid (XXX) which reacted with excess methylmagnesiurn iodide to yield the alcohol acid (XXXI). In the last reaction of this sequence some carboxylic acid was found to be converted to an alcohol ketone. This product (XXXII) was apparently formed via attack of the excess Grignard reagent (on to the salt of the acid) to yield the ketone from the acid. This alcohol ketone (XXXII) was reduced to a diol (XXXIII) and the latter converted to an acetate derivative (XXIV) 1n order to investigate its structure.
Next, the desired alcohol acid (XXXI) was pyrolyzed to give the olefin acids (XXVII) and (XXVIII) which were separated via silver nitrate impregnated silica gel column chromatography. The required intermediate (XXVII) afforded one of the necessary products or 'half molecules'.
In order to improve the overall yield of the required synthon (XXVII),
α-thujaketonic acid was quantitatively converted to the methylene derivative (LIX) via reaction with two equivalents of methyl triphenyphosphorane.⁵⁹ Pyrolytic ring opening of the cyclopropane ring system in (LIX) afforded a good yield of the dienoic acid (XXXV). Reduction of the desired acid (XXXV) with potassium in liquid ammonia gave an 85% yield of the key intermediate (XXVII).
The second required intermediate was synthesized via the esterification of
β-thujaketonic acid (XXIX) with diazomethane in ether. This yielded the ketoester (XXXVII) which was used in the following coupling reaction sequence.
Thus the key intermediate (XXVII) was treated with lithium diisopropylamide (LDA) in tetrahydrofuran (THF) to form the carboxylic acid dianion which was reacted with the keto ester (XXXVII) in THF to give a mixture of β-hydroxy carboxylic acids (XXXIX) and (XL). This product mixture was dissolved in dry pyridine and excess benzene-sulfonyl chloride was added 1n order to achieve the required cyclization to the expected olefinic β-lactones (XLI) and (XLII). Epoxidation of this mixture with metachloroperbenzoic acid (MCPBA) in methylene chloride yielded the corresponding epoxy β-lactones (XLIII) and (XLIV). The final step in the synthetic strategy was to utilize the pyrolytic decomposition of the intermediate β-lactone function to the central double bond inherent in the juvenile hormone systems. Therefore, the epoxy lactones (XLIII) and (XLIV) were subjected to such pyrolytic conditions but only decomposition products resulted. For this reason further studies with (XLIII) and (XLIV) were abandoned.
The olefin acid (XXVII) was reacted with mercuric acetate in dry alcohol and the mercury intermediate thus derived was converted with sodium borohydride in methanol or ethanol to yield respectively the methoxy (IL) or the ethoxy acids (XLVIII). The ethoxy acid (XLVIII) was reacted with LDA in THF to give the expected carboxylic acid dianion, the latter upon addition of the ketoester (XXXVII) yielded a mixture of the β-hydroxycarboxylic acids (L) and (LI). This mixture was lactonized with benzenesulfonyl chloride in pyridine as described above to yield the ethoxy β-lactones (L11) and (LI 11). These were pyrolyzed and separated to give the juvenile hormone analogues (LIV) and (LV). Analogous investigations on the methoxy acid (IL) yielded the analogous β-hydroxy carboxylic acids (LVI) and (LVII). Time constraints precluded the conversion of these to the hormone analogues. / Science, Faculty of / Chemistry, Department of / Graduate
| Identifer | oai:union.ndltd.org:UBC/oai:circle.library.ubc.ca:2429/24845 |
| Date | January 1984 |
| Creators | Leyten, Wayne J. |
| Publisher | University of British Columbia |
| Source Sets | University of British Columbia |
| Language | English |
| Detected Language | English |
| Type | Text, Thesis/Dissertation |
| Rights | For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use. |
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