Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.375448
Title: Diels-Alder approaches towards T-2 toxin and related trichothecenes
Author: Brown, Beverley Anne
ISNI:       0000 0001 3485 1696
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1986
Availability of Full Text:
Access from EThOS:
Access from Institution:
Abstract:
The trichothecenes are a group of some 80 structurally complex sesquiterpenoids of considerable environmental importance. It is difficult to obtain many of these compounds in significant amounts from natural sources, and much effort has been directed towards devising efficient, practicable syntheses of these molecules and their analogues. In the course of this research, a study of intermolecular Diels-Alder routes towards potential trichothecene precursors was carried out. Particular attention was paid to devising a general route towards T2 toxin (185), a highly oxygenated trichothecene which has yet to yield to total synthesis. To this end the cycloaddition reaction between a suitably functionalised 1,3-butadiene and an alkyl coumalate was investigated. Two major areas of study were undertaken: the Diels-Alder reaction between isoprene and a coumalic acid derivative and the cycloaddition reaction between a 2-silyloxy-substituted buta-1,3-diene and methyl coumalate. The Diels-Alder reaction between isoprene and methyl coumalate suffered from poor regioselectivity and afforded low yields of the desired adduct (157a). Significant improvements in both the regioselectivity and yield of desired adduct were obtained when coumalyl chloride (191) was employed as dienophile. Seleno- and iodolactonisation of carboxylic acid (186a) derived from adduct (157a) afforded the unexpected bicyclo [2.2.2] octane systems (192) and (195) respectively, neither of which could be converted into useful trichothecene precursors. Alternatively, bromination of the conjugate addition product (158), followed by a sequence of acetolysis and hydrolysis, furnished a 1:1 mixture of alpha-allylic alcohol (200a) and beta-allylic alcohol (200b). alpha-Allylic alcohol (200a) possesses ideal functionality for further elaboration to T2 toxin, and was accordingly converted into the corresponding gamma-lactone (203), thereby establishing the desired a-configuration of the 8-hydroxyl group. Catalytic osmylation of the conjugate addition product (158) afforded cis diol (205a) as the major product, which after a sequence of silylation, dehydration and finally fluoride-induced desilylation was transformed into the same alpha-allylic alcohol (200a)'. Cycloaddition between 2-silyloxy-substituted buta-1,3-dienes and methyl coumalate was observed to be a highly regiospecific process, affording the expected silyl enol ethers in respectable yields. In an attempt to prepare alpha-bromoketone (228) it was observed that the product obtained from bromination of the t-butyldimethylsilyl enol ether (218a) depended upon the reaction conditions employed. In the absence of pyridine the expected alpha-bromoketone was obtained. Interestingly, however, in the presence of pyridine the alpha-bromo silyl enol ether (231) was formed regioselectively.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.375448  DOI: Not available
Keywords: Organic chemistry
Share: