Synthesis of Alkoxy, Heterocyclic and Fused-Rings Derivatives of (S)-Nicotine from Natural Nicotine, Progress towards the total Synthesis of (S)-Macrostomine.

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Title: Synthesis of Alkoxy, Heterocyclic and Fused-Rings Derivatives of (S)-Nicotine from Natural Nicotine, Progress towards the total Synthesis of (S)-Macrostomine.
Author: Ondachi, Pauline Wanjiku
Advisors: Dr. Bruce M. Novak , Committee Member
Dr. Christian Melander , Committee Member
Dr. Daniel L. Comins, Committee Chair
Dr. Alexander Deiters , Committee Member
Abstract: ONDACHI, PAULINE WANJIKU. Synthesis of Alkoxy, Heterocyclic and Fused-Rings Derivatives of (S)-Nicotine from Natural Nicotine, Progress towards the total synthesis of (S)-Macrostomine. (Under the direction of Dr. Daniel Lee Comins). (S)-Nicotine and its derivatives have drawn a lot of interest due to their potential pharmacological role in the treatment of Parkinson’s disease, Alzheimer’s disease, and other central nervous system related disorders. Current synthetics efforts are directed towards the development of analogs that are more selective to specific subtypes of nicotinic acetylcholine receptors. Towards this goal, alkoxy, heterocyclic and fused-rings derivatives of (S)-nicotine were synthesized from natural nicotine as will be described herein. Methodologies were developed for the synthesis and regioselective substitution of enantiomerically pure alkoxy nicotine derivatives. Introduction of heteroaromatic rings at the C-4, C-5, and C-6 positions of the pyridine ring of nicotine and nicotine derivatives was achieved through the use of metal-catalyzed cross-coupling reactions. In addition, a variety of novel small molecules, cyclized ethers and fused-rings derivatives, were synthesized. Bicyclic dioxino, dihydrofuro and dihydropyranol nicotine derivatives, as well as tricylic benzofused-rings derivatives were synthesized as detailed in the third chapter of this document. Finally, a study directed towards the total synthesis of a plant alkaloid (S)-macrostomine was carried out. Efforts were centered on an attempt to utilize the Diels-Alder reaction to achieve a key intermediate in the synthesis.
Date: 2008-12-23
Degree: PhD
Discipline: Chemistry
URI: http://www.lib.ncsu.edu/resolver/1840.16/4224


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