From Toluene to Polyquinane natural products

Abstract

This thesis is comprised of five scientific articles and is preceded by an overview that contextualises all of the published work. The focus of the work was the development of chemoenzymatic total syntheses of several key members of the hirsutene-class of triquinane natural products from the enantiomerically pure cis-dihydrocatechol A, itself obtained through the whole-cell biotransformation of the simple aromatic compound toluene. Thus, singlehandedly, and using a combination of Diels-Alder cycloaddition and photochemically-promoted oxa-di-pi-methane (ODPM) rearrangement steps, the author has been able to convert metabolite A into the highly oxygenated triquinanes connatusin A and connatusin B. In addition he has been able to devise related methods for the synthesis of compounds D and E, the acquisition of which constitute formal total syntheses of hypnophillin and coriolin. Publication 1 of the thesis is a review article that describes how cis-dihydrocatechols such as A are produced and exploited in chemoenzymatic synthesis while Publication 2, a forthcoming book chapter, provides a survey of the applications of the ODPM and the related di-pi-methane (DPM) rearrangement reactions to the assembly of otherwise inaccessible frameworks, including those associated with polyquinanes. Publications 3, 4 and 5 are journal articles that detail the author's successfully completed total syntheses of triquinanes B, C, D and E. The Appendices to the thesis are comprised of a series reports arising from single-crystal X-ray analyses of certain key compounds synthesised by the Author. These analyses were conducted by Dr Anthony Willis, Dr Ian Cade or Mr Jas Ward, members of the Research School of Chemistry's Crystallographic Analysis Unit. Show more