Studies towards the synthesis of the C -analog of glucosyl asparagine and glyceroplasmalopsychosine.
Item
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Title
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Studies towards the synthesis of the C -analog of glucosyl asparagine and glyceroplasmalopsychosine.
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Identifier
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AAI3187438
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identifier
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3187438
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Creator
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Parhi, Ajit K.
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Contributor
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Adviser: Richard W. Franck
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Date
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2005
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Language
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English
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Publisher
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City University of New York.
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Subject
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Chemistry, Organic
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Abstract
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The C-analog of glucosyl asparagine 1.67 is among the family of artificial and biological stable carbon-linked glycopeptide building blocks, which have applications in the areas of cancer research, immunotherapy, and treatment of inflammatory responses as well as various infectious and pathogenic processes. An unsuccessful attempt to apply the Ramberg-Backlund rearrangement (RB) to connect the asparagine amino acid to the anomeric carbon atom of glucose through a carbon tether has been described in Chapter 1. During the course of the synthesis of the required sulfone 1.70 for RB rearrangement, a new 1,3-Dipolar cycloaddition reagent (Weinreb amide functionalized nitrile oxide 1.90) has been discovered. The methodology to prepare the nitrite oxide 1.90 has been successfully applied for the synthesis of another new cycloaddition reagent i.e. Weinreb amide functionalized nitrone 1.105. The scope of our new cycloaddition reagents has been extended to the synthesis of five membered heterocycles via (3+2) cycloaddition reactions with a range of dipolarophiles.;Glyceroplasmalopsychosine 2.0 is a novel glycolipid extracted from the bovine brain. In this unique glycolipid, a long chain aldehyde (plasmal) is conjugated to the primary hydroxyl group of glycerol and the 6-hydroxyl of the psychosine by an acetal linkage.;Psychosine is cytotoxic, where as glyceroplasmalopsychosine is not. This difference in cytotoxicity between the two compounds presents an interesting question concerning the pharmacological role of glycerol and long chain aldehyde. Chapter 2 describes the two different ways of synthesizing the mixed acetal segment of glyceroplasmalopsychosine. The first approach involves a non-stereospecific synthesis of the mixed acetal system by the application of Rychnovsky synthesis of alpha-acetoxy ethers from esters. The inability to separate the two acetal isomers turned our attention to the stereospecific synthesis of the mixed acetal segment of the target compound. In the second approach, the concept of converting carbohydrate to non-carbohydrate asymmetric molecules has been successfully exploited. The two isomers of mixed acetal of the target compound 2.0 have been stereo-specifically synthesized starting from two simple sugars (lyxose unit 2.66, 2.98 and galactose unit 2.67). Some of the key reactions involved in the synthesis are stereospecific O-glycosidation to prepare the required disaccharide 2.76 and 2.99, protecting group manipulations of the disaccharides to the diol 2.80 and 2.106, oxidative cleavage of diols to furnish the acetal linkage and lastly the heterogeneous Wittig reaction to construct the long aliphatic chain. The attempt to connect the sphingosine side chain to the acetal segment of the target molecule was not successful.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
