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Title: Investigations on the synthesis of natural allenic and acetylenic systems
Author: Jones, J. B.
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 1960
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(i) Odyssic acid and odyssin were isolated in 1955 by Jones and his collaborators from cultures of the Basidiomycete "B841", and were assigaed the structures (IV; R=H) and (V) respectively on the basis of degradative studies. Although work on the synthesis of the two compounds could be justified on the grounds of confirmation of structure alone, other factors wore also of importance, e.g. investigation of the antibiotic activity was desired. Owing to the sensitivity of the allene-acetylene system present in odyssin, the following synthetic scheme was devised in which the allene was to be introduced in the final step. Condensation of ethynylmagnesium bromide with β-carbethoxypropionaldehyde gave a 50% yield of the hydroxy-ester (I; R=H, R′=Et), which was then hydrolysed quantitatively to the free acid (I; R=R′=H). Attempted coupling of both the free acid (I; R=R′=H) and the protected acid (I; R=2′-tetrahydropyranyl; R′=H), as the bromo-magnesium derivatives, with the bromide (II; X=Br) in the presence of cuprous chloride gave none of the required product (III) even though model work on hydrocarbons had been successful. Attention was then focussed on an alternative preparative route to the ≡C.CH2.C≡ system which incorporated the reaction of an acetylenic Grignard reagent with a βγ-acetylenic sulphonate. As preferential reaction with the halogen anion of the bromo-magnesium destroyed half the sulphonate, model experiments were carried cut with halogen free dialkynylmagnesium solutions. Dihex-1-ynylmagnesium and the tosylate (II; X=p-SO3.C6H4.CH3) reacted to the extent of 65%, but the product when isolated had rearranged to a mixture of all the possible isomers, the composition of which is given below. Application of the model conditions to the magnesium derivative of the protected acid (I; R=2&prime-tetrahydropyranyl; R′=H) and the above tosylate in ether gave a heterogeneous reaction mixture which, after isomerisation, afforded only a 0.0006% yield of 2′-tetrahydropyranyl odyssic acid (IV; R=2′-tetrahydropyranyl), In tetrahydrofuran, a homogeneous solution was obtaine, but the doncitions required to replace the ethynyl proton of the protected acid (with diethylmagnesium) resulted in the conversion of the carboxyl group to an ethyl ketone. (ii) Odyssin and odyssic acid were known to undergo alkali-catalysed isomerisation to odyssin A (VIII) and iso-odyssic acid (VI) respectively. The synthesis of the two isomers and also of iso-odyssic lactone (VII) was accomplished by the scheme outlined overleaf. (iii) The difficulties associated with the synthesis of polyacetylenes are considerably increased when cis-double bonds are present as the most convenient starting materials, viz. alcohols and acids with cis-ethylenic linkages, are tedious to purify and are readily cyclised acidic and basic conditions. The possibility of using the well known photochemical isomerisation of double bonds as a preparative method for converting the more readily available trans-polyacetylenes into the cis-forms was therefore investigated. Two examples only of photoequilibration in the polyacetylene field had been reported, both being cis to trans conversions. In 1941, Sórensen et al. discovered that cis-matricaria ester (IX) could be photoisomerised to the "trans"-compound (X), and eighteen years later, the sulphur compound (XI) was converted into (XII) by irradiation. It was considered that trans to cis conversion should also be possible, and as the above isomerisations had been effected with double bonds conjugated to an ester group, this type of system was selected for the initial studies. trans-Lachnophyllum ester (XIII), on Irradiation (λ > 2900 Å) in light petroleum was mainly converted (80%) into the cis-isomer (XIV). Chromatography on alumina gave a 60% yield of the pure cis-ester. It was of interest to discover whether or not the ester activation could be relayed by an acetylenic chain. For this purpose the trans-ester (XV) was used. It was readily photoisomerised (under the above conditions) to a mixture which was shown by vapour phase chromatography to consist of 45% of the cis- and 55% of the trans-compound. Preparative scale experiments were not attempted as decomposition of the L cis-ester (XVI) occurred during chromatographic purification. An ethylenic system with acetylenic activation only was considered next. trans-Dehydromatricarianol (XVII) was irradiated (λ > 2200 Å) in ethanol and was partly converted (27%) into the cis-isomer. (XVIII). A portion of the latter had cyclised during the experiment to give the dihydrofuran. (XIX) (10% overall) which on careful chromatography was resolved into its 4,5-double bond isomers. The structure of (XIX) was authenticated by comparison of its ultraviolet spectrum with that of a synthetic spectrum of the new chromophore.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available