The Synthesis of Potential Antitumour Compounds

Peden, Allison (1990) The Synthesis of Potential Antitumour Compounds. PhD thesis, University of Glasgow.

Abstract

The work carried out in this thesis concerned the synthesis of the fungal metabolite, duclauxin, and other potential antitumour compounds. The synthetic approach to duclauxin was to synthesise a pyrano [1,8-c]naphthalen-1(3H)-one derivative and then dimerise it to a derivative of duclauxin. The key step in the synthesis was treatment of the ethylene acetal of acetoacetyl chloride with the anion of methyl 3,5-dimethoxyphenylacetate to give the 5-ethylene acetal of methyl 2-(3,5-dimethoxyphenyl)-3,5-dioxohexanoate. Treatment of this acetal with acid gave methyl 2-hydroxy-5,7-dimethoxy-4-methyl naphthalene-1-carboxylate as the only product. This naphthalene was methylated to give methyl 2,5,7-trimethoxy-4-methyl naphthalene-1-carboxylate which when treated with methoxyacetyl chloride and tin(IV)chloride gave the desired lactone, 4,6,9-trimethoxy-7-methyl pyrano[1,8-c]naphthalen-1(3H)-one. Boron tribromide and aluminium chloride were used to cleave one of the methoxy ethers in this lactone. A series of potential antitumour, phosphorus heterocycles were prepared. Their activities will be tested and compared. The most important step in their synthesis was treatment of the appropriate ester with the anion of ethyl phosphonic acid bis(dimethylamide) and then treating this beta-ketophosphonamide with boron tribromide to give the corresponding cyclic phosphonate. The synthesis of the fungal metabolite, differanisole A, another potential antitumour compound, was completed. The main difficulty in this synthesis was the first step which was to cleave the ethyl ester group of ethyl 3,5-dichloro-2- hydroxy-4-methoxy-6-propylbenzoate. This was achieved by treatment with cold concentrated sulphuric acid at 0

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Organic chemistry, Pharmaceutical sciences
• Date of Award: 1990
• Depositing User: Enlighten Team
• Unique ID: glathesis:1990-78193
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 30 Jan 2020 15:37
• Last Modified: 30 Jan 2020 15:37
• URI: https://theses.gla.ac.uk/id/eprint/78193