Progress towards enantioselective total synthesis of the bisbenzyltetrahydroisoquinoline alkaloid (-)- cycleanine and a new approach to the syntheses of some isoquinolones

Cui, Jianwen (2003) Progress towards enantioselective total synthesis of the bisbenzyltetrahydroisoquinoline alkaloid (-)- cycleanine and a new approach to the syntheses of some isoquinolones. Masters thesis, Memorial University of Newfoundland.

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Abstract

Bisbenzylisoquinoline (BBIQ) alkaloids are a very large and structurally diverse family of compounds, which can exist in up to 28 possible types. These compounds have been isolated from a variety of different plant sources and are found to exhibit a multitude of pharmacological properties including antitumor, antimalarial, and antibacterial activities. Variation in the number of oxygen substituents on the aromatic rings present, the number of ether linkages, the nature of the ether bridges and the sites on the two benzylisoquinoline units where the ether or carbon-carbon bonds originate, have made BBIQ's very interesting targets for several synthetic endeavours. -- The research described herein focuses on the asymmetric synthesis of the BBIQ(-)-cycleanine, and several other compounds of interest. The mild Cu(OAc)₂-promoted diaryl ether formation methodology was applied to construct the target molecule. Crystals of the key precursor to the diaryl ether formation step were obtained and the absolute configuration of a new stereogenic center was established based on the X-ray crystallography analysis. The use of a chiral auxiliary-assisted diastereoselective Bischler-Napieralski cyclization is discussed. -- In addition, a new approach to the synthesis of isoquinolones thalifoline, corydaldine and N-methylcorydaldine is investigated utilizing the Bischler-Napieralski strategy for the isoquinolines formation. Furthermore, regioselective oxidation of tetrahydroquinolines by using RuO₂-NaIO₄ is explored.

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