Biomimetic synthesis of a novel nonadride natural product

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Project objective

Research objectives and content Recently two new biologically active natural products based on nonadridic structures were isolated and characterised. Retro-biosynthetic analysis indicates that these seemingly complex products may be derived from the dimerisation of two closely related and simpler anhydride sub-units.We wish to attempt to reduce the synthesis of nonadride derivatives (comparable to the isolated natural products), to a (4+6)-cycloaddition of suitable precursors as the key step of a short biomimetic synthetic approach.Alkenylated aconitic acid esters and maleic anhydride derivatives containing different sidechains should be obtained starting from dihalogenated maleic anhydride by two consecutive tin-based coupling reactions, or a tin-based coupling reaction and a subsequent addition/elimination reaction, using easy accessible organotin reagents under mild conditions. After consecutive deprotection, decarboxylation and deprotonation of the derived aconitic acid esters, or after deprotonation of suitable maleic anhydride derivatives, a suprafacial, suprafacial (4+6)-cycloaddition with aconitic acid esters should form nonadridic anions as key intermediates, which should be converted in situ into the desired products via intramolecular cyclisation. Training content (objective, benefit and expected impact) The objective of this research project is to develop a straightforward synthesis of derivatives of biologically active natural products. The combination of various modern tranformations of organometallic chemistry to a total synthesis and the structural characterisation of intermediates and final products will extend the synthetic experience of the applicant. Links with industry / industrial relevance (22) The obtained products will be tested for biological activity in collaboration with Glaxo-Wellcome plc.

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Participants

• THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD · OXFORDCoordinatorUnited Kingdom

Links

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