Enantioselective syntheses of novel analogues of sphingolipids and glycerolipid precursors.
Item
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Title
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Enantioselective syntheses of novel analogues of sphingolipids and glycerolipid precursors.
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Identifier
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AAI9969694
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identifier
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9969694
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Creator
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He, LinLi.
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Contributor
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Adviser: Robert Bittman
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Date
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2000
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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 sphingolipids and analogues bearing modifications in the sphingoid backbone. Also included in this dissertation are novel methodologies for the preparation of precursors of ether-linked glycerolipids.;Chapter 1 presents a general synthetic strategy for the synthesis of sphingolipids. This strategy involves the following three major reactions: (1) catalytic asymmetric dihydroxylation of alpha,beta-unsaturated esters, (2) regioselective azide substitution with inversion at the alpha position of the resulting alpha,beta-dihydroxyester, and (3) simultaneous reduction of the triple bond, azido, and ester functional groups with lithium aluminum hydride. Highly enantioselective and efficient syntheses of D-ribo-phytosphingosine [(2S, 3S,4R)-2-aminooctadecane-1,3,4-triol, 45% overall yield], D-erythro-sphingosine [(2S,3R,4E)-2-amino-1,3-dihydroxyoctadec-4-ene, 25% overall yield], and D-erythro-sphinganine [(2S,3R)-2-aminooctadecane-1,3-diol, 73% overall yield] from simple achiral starting materials have been achieved.;Chapter 2 presents a one-pot regioselective azidation reaction of 1,2- and 1,3-diols with triphenylphosphine, diisopropyl azodicarboxylate, and azidotrimethylsilane under Mitsunobu conditions. This highly stereospecific reaction introduces the azide ion to the more hindered C(2) or C(3) position of a 1,2- or 1,3-diol, respectively.;Chapter 3 presents the synthesis of a new analogue of ceramide, D-erythro-trans-Delta5-ceramide [(2S,3R,5E)-N-acyl-2-amino-1,3-dihydroxyoctadec-5-ene]. This novel ceramide analogue, which contains a C(5)-C(6) trans double bond instead of the naturally occurring C(4)-C(5) trans double bond, did not promote the fusion of Semliki Forest virus (SFV) in a liposomal model system. The results presented in Chapter 3 indicate that there is an absolute requirement for the C(4)-C(5) trans double bond for the fusion of SFV with target membranes.;Chapter 4 presents a novel chiral synthon, (S)-1-(4 '-methoxyphenyl)glycerol 2,3-cyclic sulfate, and some of its applications in the efficient syntheses of four glycerolipid precursors. Also presented is a very efficient conversion of (S)-1-(4 '-methoxyphenyl)glycerol to p-methoxyphenyl (R)-oxiranylmethyl ether, another important C-3 synthon.;Chapter 5 presents a simple and efficient method for the preparation of a chiral alpha,beta-epoxyester, an important chiral building block for the synthesis of natural and/or unnatural products.
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Type
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dissertation
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Source
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PQT Legacy Restricted.xlsx
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degree
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Ph.D.