Biomimetic Orientated Total Synthesis of Neovibsane Natural Products and Comparison of Synthetic Neovibsanes on Neurite Outgrowth Promotion in PC12 Cells

Annette Chen (2010). Biomimetic Orientated Total Synthesis of Neovibsane Natural Products and Comparison of Synthetic Neovibsanes on Neurite Outgrowth Promotion in PC12 Cells PhD Thesis, School of Chemistry & Molecular Bioscience, The University of Queensland.

       
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Author Annette Chen
Thesis Title Biomimetic Orientated Total Synthesis of Neovibsane Natural Products and Comparison of Synthetic Neovibsanes on Neurite Outgrowth Promotion in PC12 Cells
School, Centre or Institute School of Chemistry & Molecular Bioscience
Institution The University of Queensland
Publication date 2010-02
Thesis type PhD Thesis
Supervisor Craig Williams
Ross McGeary
Total pages 226
Total colour pages 16
Total black and white pages 210
Subjects 03 Chemical Sciences
Abstract/Summary Neovibsanin A and B are natural products which induced neurite outgrowth in PC12 cells. They belong in the neovibsane class under the rare vibsane natural product family, whose structures are characterized by polycyclic, polyoxygenated cores. Based on a proposed biosynthesis, the synthetic strategy towards neovibsanin A and B involved synthesizing a key enone intermediate. Initial investigation using this intermediate lead to the total synthesis of 2-O-methylneovibsanin H. Crucial to this concise synthesis was an acid-catalyzed, one-pot, four-step cascade reaction. Modifying the reaction condition leads to a different five-step cascade pathway, resulting in the total synthesis of 4,5-bis-epi-neovibsanin A and B. The synthetic trials and tribulations encountered on the road to these final compounds are explored. It is envisaged that other related neovibsane natural products may arise based on this synthetic sequence. 4,5-Bis-epi-neovibsanin A and B, as well as several other structural analogues collected during the synthesis, were biologically assayed using NGF-stimulated PC12 cells. All compounds induced a significant proportion of neurons to extend neurite processes compared to control cultures. The structure-activity relationship studies indicated that the tricyclic core, as well as the 3,3-dimethylacroyl enol ester side chain, may be responsible for promoting a biological response.
Keyword neovibsanin a
neovibsanin b
2-O-methylneovibsanin h
biological activity
neurite outgrowth
natural product
total synthesis
Additional Notes page numbers to print in colour pages 26,83,86,95,97,130,131,135,219-226.

 
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