Synthetic and Rearrangement Studies in the Terpenoid Field

Mills, Roy W (1972) Synthetic and Rearrangement Studies in the Terpenoid Field. PhD thesis, University of Glasgow.

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Section A. Synthesis of (+)-trans-Chrysanthemic Acid and some Analogues. (+)-trans-Chrysanthemic acid is the major acidic hydrolysis product of the pyrethrins, a group of six naturally occurring esters which exhibit important insecticidal properties. Its structure contains a cyclopropane ring bearing a gem-dimethyl grouping and a carboxylic acid function which is trans to an isobutenyl side-chain. Synthetic pyrethrins, often with improved insecticidal properties, are obtained by esterifying the appropriate alcohol with (+)-trans-chrysanthemic acid or a suitable analogue. A flexible and potentially commercial synthesis of this racemic acid is herein described, in which both isoprenoid "halves" of the monoterpenoid skeleton are essentially derived from the same starting material, 2-methylbut-3-yn-2-ol. Since this alcohol is effectively obtained by reaction of acetylene with acetone, this versatile synthesis is based upon inexpensive starting materials. Treatment of readily derived 3-chloro-3-methylbut-1-yne with strong base in the presence of 3,3-dimethyl-allyl alcohol, afforded dimethylallenecarbene, which reacted in situ with the double bond of the allylic alcohol to give 2-(2'-methylpropenylidene)-3,3-dimethyl-cyclopropanemethanol. This allenic cyclopropane contains the essential structural elements of the chrysanthemic acid skeleton, with however an additional double bond, and a primary hydroxyl group where a carboxylic acid function is required. Regioselective and stereoselective reduction of the cyclopropyl double bond was effected with sodium in liquid ammonia, producing a high yield of racemic chrysanthemyl alcohol of which over 75% was the required trans isomer. A variety of oxidizing conditions was investigated during attempts to convert chrysanthemyl alcohol to the acid, but many proved unsuccessful due to the sensitivity of the chrysanthemyl molecule to acidic conditions. The desired oxidation was, however, effected using chromium trioxide in pyridine, racemic chrysanthemic acid being obtained without loss of stereochemical integrity. The synthesis was adapted for the production of chrysanthemic acid analogues. The use of 1-ethynylcyclohexyl chloride and 1-ethynylcyclopentyl chloride led to the expected acids, while oxidation of the intermediate allenic alcohols provided the first available synthesis of allenic derivatives. Attempts to effect the carbene addition reaction on 3,3-dimethylacrylic acid and related compounds proved unsuccessful. Section B. Acid-catalysed Rearrangement of a Diterpenoid Epoxide. Treatment of erythroxylol A epoxide, a naturally occurring tetracyclic diterpenoid of the beyerane series with 95% formic acid, led to the formation of at least seventeen products. It was shown that these resulted from two distinct concentration dependent rearrangement pathways, one of which was analogous to the previously established hibaene epoxide rearrangement which produces compounds of the kaurane series. This route accounted for four of the identified products whose structures were elucidated both spectroscopically and chemically. Their interconvertibility was demonstrated by hydrolysis and dehydration experiments. At higher concentrations of the epoxide in formic acid, the major product was an enediol monoformate which was shown spectroscopically and chemically to contain an allylic secondary alcohol grouping, probably in ring It v/as readily oxidized to a conjugated cyclohexenone, while reduction experiments demonstrated its close structural relationship to dihydroerythroxylol A, the fully-saturated parent compound of the starting epoxide. A possible mechanism for its formation is suggested which could conceivably account for the remaining rearrangement products, some of which were isolated and assigned tentative structures.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Organic chemistry
Date of Award: 1972
Depositing User: Enlighten Team
Unique ID: glathesis:1972-78601
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 30 Jan 2020 15:08
Last Modified: 30 Jan 2020 15:08

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