Faculty of Science School of Chemistry 9800165e govendor@aurum.wits.ac.za / Pyranonaphthoquinones are biologically important molecules found in a wide variety of bacteria, microbial fungi and plant species. Their biological activity is proposed to be a consequence of their ability to function as bioreductive alkylating agents. This class of compounds, which include monomeric and dimeric examples, contain the basic naphtho[2,3-c]pyran-5,10-dione skeleton, usually with substituents at the C-1 and C-3 positions of the pyran ring. The aim of the first part of the project was to develop a novel method for the synthesis of enantiomerically pure 5,8-dimethoxy-isochroman-4-ol, which will provide a handle for stereoselectively adding substituents to the C-1 and C-3 positions of the pyran nucleus. In the second part of the project we wished to attempt to synthesize the naturally occurring compound, cardinalin 3, the dimer of ventiloquinone L previously synthesized in the Wits laboratories. The synthesis of the enantiomerically pure isochromanol began with 2,5-dihydroxybenzoic acid, which was subjected to a diallylation followed by a Claisen rearrangement. The phenols were protected by a methylation reaction and the ester moiety was reduced to give (2-allyl-3,6- dimethoxyphenyl)methanol. It was then allylated to produce a suitable precursor for a one pot/two step ruthenium mediated isomerisation/ring closing metathesis reaction to produce 5,8-dimethoxy-1H-isochromene in an overall yield of 47%. It was converted to racemic 5,8-dimethoxy-isochroman-4-ol through a hydroboration-oxidation reaction in a yield of 84%. The separation of the enantiomers was achieved by acetylating the alcohol to form 5,8-dimethoxy-3,4-dihydro-1H-isochromen-4-yl acetate and then a lipase enzyme was used to stereospecifically deacetylate one enantiomer, while leaving the other enantiomer untouched. The second part of the dissertation discusses the progress towards the synthesis of cardinalin 3. This project began with the formation of the C-C biaryl axis starting from 1,3-dimethoxybenzene. The synthesis then continued with the diformylation of the biphenyl to give 2,2’,6,6’-tetramethoxy[1,1′-biphenyl]-3,3′-dicarbaldehyde. This was subjected to a Stobbe condensation and a Friedel-Crafts acylative cyclisation to produce diethyl [4,4′-diacetoxy-6,6′,8,8′-tetramethoxy-7,7′-binaphthalene]-2,2′- dicarboxylate. The synthesis will be continued in the PhD, using methodology previously developed for the formation of the monomer, as well as methodology developed here.