Novel syntheses of sphingolipids and their analogues.
Item
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Title
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Novel syntheses of sphingolipids and their analogues.
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Identifier
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AAI3187442
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identifier
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3187442
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Creator
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Lu, Xuequan.
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Contributor
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Advisers: Robert Bittman | Gerald W. Koeppl
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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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This dissertation presents the asymmetric total syntheses of naturally occurring sphingoid bases and novel sphingolipid analogues, including (a) photoactivatable sphingosine 1-phosphate (S1P), (b) photoactivatable sphingosylphosphorylcholine (SPC), (c) phytosphingosine 1-phosphonate, (d) a ceramide bearing a C4-methylene group, (e) chiral phosphates and phosphonates of FTY720, and (f) an alpha-C-glycoside of the KRN7000. Also included in this dissertation is a novel synthesis of a beta-C-glycoside analogue of the ether lipid ET-18-OCH3.;Chapter 1 presents the first synthesis of two [32P]-labeled photoaffinity probes of sphingosine 1-phosphate (S1P): (2S,3 R)-14-(O)-(4'-benzoyl)phenyl- and 14-(O)-(4'-trifluoromethyldiazirinyl)phenyl-4( E)-tetradecen-2-amino-3-hydroxy-1-phosphate.;Chapter 2 presents the synthesis of the first photoaffinity analogue of SPC. This probe, which contains a 14C-isotopic label in the choline methyl groups and a benzophenone in the long-chain base, may be a useful tool in the identification of receptors that have been postulated to interact directly and specifically with SPC.;Chapter 3 presents the first synthesis of an isosteric phosphonate analogue of the aminotriol lipid (2S,3S,4 S)-phytosphingosine, together with an improved synthesis of (2 S,3S,4S) and (2S,3 S,4R)-phytosphingosine. A key intermediate is a 3-pentylidene acetal.;Chapter 4 presents the synthesis of a new analogue of (2S,3 R)-ceramide with a methylene group at C4. Tebbe methylenation was the key step in the synthesis.;Chapter 5 presents efficient routes to the synthesis of (2S,3 R)-2-azido-3-O-benzylsphingosine and (2S,3 R)-sphingosine from (2R,3S)-2- O-benzyl-3,4-O-(3'-pentylidene)-2,3,4-trihydroxybutanal, which was prepared from D-tartaric acid.;Chapter 6 presents a concise synthesis of FTY720 and the first syntheses of its chiral phosphonate and regioisomeric analogues. A 2,3-epoxy alcohol served as a common precursor of these targets. An intramolecular reaction of a 2,3-epoxytrichloroacetimidate mediated by Et2AlCl gave a five-membered oxazoline ring, which created the quaternary center.;Chapter 7 presents a short synthesis of a new beta-C-gaactosyl analogue of ET-18-OCH3 via the addition of a chiral propargylic alcohol to 2,3,4,6-tetra-O-benzylgalacto-delta-lactone.;Chapter 8 presents the first synthesis of a alpha-C-galactosylceramide analogue that is tentatively assigned to bear an D-arabino-phytosphingosine backbone. The method has only 11 steps (or 13 steps with the final acylation and deacylation) in the longest pathway and an overall yield of 8.8%.
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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.
