Degree Type

Dissertation

Date of Award

2016

Degree Name

Doctor of Philosophy

Department

Chemistry

Major

Chemistry

First Advisor

Jason Chen

Second Advisor

George Kraus

Abstract

Various natural products have been isolated with promising bioactivities but in very small quantities, impeding structure elucidation and structure activity relationship studies. Therefore, synthesis of such natural products in laboratory becomes very important for structure determination and biological studies. Two isomeric oxylipins (a trihydroxy fatty acid) were isolated from the Peruvian plant Dracontium lortense in very minute quantities (1 mg of each). One of the oxylipins have shown promising activity as an immunostimulant. Although the relative stereochemistry of the natural product was assigned, due to scarcity the absolute configuration was unknown. The current work describes the synthesis and structural assignment of these unnamed isolated oxylipins.

The first chapter describes a synthesis of all stereoisomers of this natural product using a method develop to synthesize chiral 1,2-diols. Anti 1,2-diols were prepared from simple inexpensive aldehydes via aldehyde α-oxygenation followed by organomagnesium or organolithium addition. All the diastereomers were synthesized and the stereochemistry of the naturally occurring oxylipins were unambiguously assigned using NMR spectroscopy.

The second chapter describes a more direct and convergent synthesis of this natural product using an olefin cross metathesis approach. The natural product was synthesized in just three steps starting from cheap and readily available starting materials in 33% overall yield. Our synthesis is by far the shortest synthesis of this class of natural products containing the 3-ene-1,2,5 triol moiety.

The third chapter describes the studies towards structure elucidation of different diastereomers of 2,2,6,6-tetramethylpiperdine singly masked 1,2-diols. Observed disparity in the hydroxyl proton 1H-NMR chemical shifts of diastereomers of singly masked 1,2-diols led us to collaborate with computational chemists at Iowa State University (Professor Theresa Windus) to determine conformations of singly masked 1,2 diols. Computational (RHF, DFT, MP2) and 1D (decoupling experiments) and 2D NMR (HETLOC, HMBC) spectroscopic analysis revealed different hydrogen bonded ground state conformations of different diastereomers. This chemical shift difference was observed in various solvents and could be used as an stereochemical probe. The sterics of the gem dimethyl groups of the 2,2,6,6-tetramethylpiperdine moiety appears to be the reason behind this conformational preference.

DOI

https://doi.org/10.31274/etd-180810-5519

Copyright Owner

Shreyosree Chatterjee

Language

en

File Format

application/pdf

File Size

200 pages

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