Abstract
Coumarin (benzopyran-2-one) and its derivatives are widely distributed throughout nature. They are secondary metabolites produced from plants with different medicinal properties. In drug discovery, drugs that are potent against bacteria have been discovered through natural plant products isolated from different plant species. Two coumarin natural plant products with such a potential were isolated from respective plant species namely meranzin hydrate coumarin from Muraya paniculata and ulopterol coumarin from Coleonema album . The aim of the project is to synthesize meranzin hydrate and ulopterol coumarins through basic reaction methodologies. It was proposed that they could have a better potency towards bacteria species because of the diol functional groups from the isopentyl side chain or the increased oxygen content. Similar reaction conditions were employed to construct the two regio-isomers. Regioselectivity and enantioselectivity were the challenges to be addressed from the project. The key reaction was Claisen rearrangement reaction of the allyl ether of the allyloxy coumarin used to synthesize an ortho carbon-carbon bonds from the umbelliferone but the McMurry reaction and Wittig reactions failed to yield suberosin and osthol. The Heck cross coupling reaction was used as an alternative for the Claisen rearrangement reaction and the iodo-coumarin substrates from umbelliferone were used in Heck cross coupling reaction to form the desired alkenes of murraol and suberenol. The resulting alkenes were epoxidized which lead to a chemoselective reaction which produced the desired alcohol and leading to the diol functional groups found in both ulopterol and meranzin hydrate. Enantioselective reactions of ulopterol and meranzin hydrate were done with the use of an AD-mix (alpha andbeta ) reagents on suberosin and osthol from their alkene functional groups. Meranzin hydrate precursors are easy to obtain compared to those of ulopterol. Minimum inhibition concentrations of both regioisomers and their enantiomers were assessed on several gram-positive and gram-negative bacteria species and the R -conformer of meranzin hydrate enantiomer was the best of the four isomers.
M.Sc. (Chemistry)