Asymmetric syntheses of new analogues of ceramide.
Item
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Title
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Asymmetric syntheses of new analogues of ceramide.
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Identifier
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AAI3074638
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identifier
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3074638
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Creator
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Chun, Jiong.
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Contributor
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Adviser: Robert Bittman
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Date
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2003
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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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This dissertation presents the asymmetric total syntheses of natural occurring ceramides and analogues bearing modifications in the sphingoid backbone. Also included in this dissertation is a novel methodology for the preparation of chiral propargylic alcohols.;Chapter 1 presents the syntheses of ceramide analogues in which the trans double bond of natural occurring ceramide is incorporated a benzene or pyridine ring. Two efficient and stereoselective routes are described. The first route involves the addition of an aryllithium or a heteroaryllithium reagent to an L-serine-derived aldehyde, followed by hydrolysis of the oxazolidine, liberation of the amino group, and N-acylation. The second route utilizes a Heck reaction to afford an (E)-alpha,beta-unsaturated ester, then Sharpless asymmetric dihydroxylation for the construction of the desired chirality.;Chapter 2 presents a simple and convenient method for the regiospecific introduction of unsaturation (both as a single trans double bond and as a conjugated diene) into the sphingoid backbone of ceramide by employing organosulfur chemistry. C-Alkylation of a beta-ketosulfoxide and elimination of PhS(O)H provided a conjugated ketone.;Chapter 3 presents the synthesis of a new analogue of ceramide with deuterium in the sphingoid backbone for quantification of sphingosine 1-phosphate in biological samples by stable isotope dilution mass spectrometry. Addition of lithium pentadecyne-d27 to Garner aldehyde in the presence of HMPA resulted in high erythro selectivity.;Chapter 4 presents the first synthesis of the 5R and 5S diastereoisomers of the N-acyl derivatives of 5-hydroxy-3-sphingosine, which represent regioisomers of natural occurring 2S,3R-ceramide. The key steps include the synthesis of alpha,beta-unsaturated ketone intermediates from N-Cbz- and N-Boc-L-serine and diastereoselective reduction of the enones.;Chapter 5 presents the first synthesis of the 6S and 6R diastereoisomers of 6-hydroxy-4-sphingenine-containing ceramides, which were found recently in human skin. Chiral propargylic alcohols were prepared via Sharpless asymmetric dihydroxylation of an alpha,beta-unsaturated ester and allylic chloride.;Chapter 6 presents a simple and efficient method for the preparation of chiral propargylic alcohols which are important chiral building blocks for the synthesis of natural and unnatural products.;Chapter 7 presents the syntheses of ceramide analogues in which the trans double bound of naturally occurring ceramide was changed to an allene. (Abstract shortened by UMI.).
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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.
