Stereoselective synthesis of artificial C-nucleosides

Stambasky, Jan (2008) Stereoselective synthesis of artificial C-nucleosides. PhD thesis, University of Glasgow.

Abstract

Reported herein is a conceptually new synthetic route to 1’-aryl C-ribofuranosides and their 2’,3’-didehydro 2’,3’-dideoxy (D4) analogues. We have successfully implemented a divergent synthetic route capable to reach two important, biologically significant groups of compounds. The first two strategic transformations are common for both families of target compounds (asymmetric allylic substitution, and ring-closing metathesis). D4 C nucleoside analogues are synthesised in a three step procedure, and 1’-aryl ribofuranoses are constructed in a four step procedure.
The target compounds were prepared in an excellent enantio and diastereopurity, in good overall yields. The yield in the synthesis of 1’-aryl-2’,3’-didehydro-1’,2’,3’-trideoxyribofunanoses is up to 46% over all the reaction steps. The overall yield of the 1’-arylribofuranoses is up to 42%. All the strategic transformations rely on catalytic oranometallic reactions employing group 8a transition metals. All the reactions have been optimized with a view of maximal atom efficiency and environmental impact. In summary, our new methodology is perfectly suitable for the synthesis of 1’ arylribofuranoses, and their D4 analogues, bearing non-ortho-substituted aromatics and hereroaromatics, lacking coordinating (nitrogen) substituents or heteroatoms. In this point of view the most promising target application is the synthesis of lipophilic isosters of ribonucleosides for the RNA studies.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: C-nucleosides, iridium, organometallic, synthesis, catalytic
• Subjects: Q Science > QD Chemistry
• Colleges/Schools: College of Science and Engineering > School of Chemistry
• Supervisor's Name: Kocovsky, Prof. Pavel
• Date of Award: 2008
• Depositing User: Mr. Jan Stambasky
• Unique ID: glathesis:2008-198
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 25 Jun 2008
• Last Modified: 10 Dec 2012 13:16
• URI: https://theses.gla.ac.uk/id/eprint/198