Synthesis of xanthoxal.
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Date
1999
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Abstract
The aim of this project was to synthesize xanthoxal, a natural product which is a possible abscisic acid precursor. The xanthoxal will serve as a vital link: in a study on the biosynthesis of abscisic acid in plants. This study does not form part of this thesis. The synthetic pathway begins with mesityl oxide and ethyl acetoacetate as starting materials, and the target molecule was obtained via a I3-step route. The first step involved a Robinson annulation, which afforded the ketal of a ClO-ester ketone (ethyl2,6, 6-trimethyI4-oxo2-cyclohexene-I-carboxylate) which has a cyclohexene structure. The double bond in the 2,3 position of the ClO-ester ketone was isomerised to the 1,2 position followed by the simultaneous protection of the ketone, in the form of a ketal. The ester function of the ClO-ester acetal underwent reduction to afford an allylic alcohol
. on which an asymmetric Sharpless epoxidation was carried out using (-) diethyl tartrate affording (+)-(1R, 2R)-I,2-Epoxy-4, 4-ethylenedioxy-2,6, 6-trimethylcyclohexane-lmethanol. The alcohol was oxidised by a Swem oxidation to the aldehyde in order to carry out a chain elongation. The side chain was prepared from 3,3-dimethylacrylic acid, which was first esterified then brominated to 4-bromosenecioate. The bromine was then replaced with triethyl phosphite, producing the Cs-phosphonate. Chain elongation by
Homer-Emmons reaction was carried out on the aldehyde with the phosphonate, which resulted in a mixture ofE and Z CIs-esters. Since the yield of tht desired Z isomer, was very low, the E isomer was used to synthesize trans-xanthoxal, since this can be converted to the desired xanthoxal by uv radiation. The acetal was then removed followed by a simultaneous reduction of the ketone and ester groups to their
corresponding alcohols using DffiAH. This reaction was only partially successful because only the keto group was reduced. The ester was then reduced with LiAIHt to form the primary alcohol, which was then selectively oxidised to the target molecule, the aldehyde (trans-xanthoxal).
The synthesis of xanthoxal described here highlights the difficulties encountered when introducing the requisite functional groups on the cyclohexene ring skeleton to afford trans-xanthoxal. The pitfalls encountered during the reaction sequence are discussed and solutions are presented. Although the planned synthetic sequence did not produce the
correct stereoisomer, procedures are available to convert it to the desired isomer.
Description
Thesis (M.Sc.)-University of Natal, Pietermaritzburg, 1999.
Keywords
Xanthoxal--Synthesis., Theses--Chemistry.