Further progress towards enantioselective total synthesis of the bisbenzyltetrahydroisoquinoline alkaloid (-)-cycleanine

Zhou, Ningzhang (2004) Further progress towards enantioselective total synthesis of the bisbenzyltetrahydroisoquinoline alkaloid (-)-cycleanine. Masters thesis, Memorial University of Newfoundland.

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Abstract

Bisbenzylisoquinoline (BBIQ) alkaloids are a large group of compounds which outnumber those of most of the other alkaloid families. These compounds occur in many different plants and usually display a variety of pharmacological properties such as antitumor and antibacterial activities. The two benzylisoquinoline subunits in BBIQs can be connected through an oxygen atom or by carbon-carbon linkage. The subunits may have the same or opposite configurations at their asymmetric centres. BBIQs may also contain dihydroisoquinoline or tetrahydroisoquinoline units. A vast number of possible structures may be constructed in this way which make BBIQs very interesting synthetic targets. -- In this thesis, the asymmetric synthesis of the BBIQ (-)-cycleanine was attempted. A chiral auxiliary-assisted diastereoselective Bischler-Napieralski cyclization was used to form the two correct tetrahydroisoquinoline subunits. Two different methods of recently reported improved Ullmann coupling methods, namely (a) N,N-dimethylglycine promoted coupling, and (b) 2,2,6,6-tetramethylheptane-3,5-dione-accelerated coupling were first employed to build the framework of the target molecule. The use of a methodology of using a mild SNAr reaction between phenols and electron-deficient aryl fluorides was also evaluated. In addition, some efforts at making some intermediates for the total synthesis more synthetically accessible are also discussed.

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