Syntheses of isotope-labeled fatty acids, plasmalogen and its analog, and unsaturated dequalinium analogs.
Item
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Title
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Syntheses of isotope-labeled fatty acids, plasmalogen and its analog, and unsaturated dequalinium analogs.
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Identifier
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AAI9917689
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identifier
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9917689
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Creator
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Qin, Donghui.
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Contributor
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Adviser: Robert Bittman
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Date
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1999
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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 syntheses of half-deuterated palmitic and palmitoleic acids specifically deuterated at different regions are described. The key step was the opening of the ring of perdeuterotetrahydrofuran by a halotrimethylsilane (TMSX, where X = I, Br), followed by treatment with 3,4-dihydro-2H-pyran gave two stable difunctional synthons THPO(CD2)4X. These synthons were cross-coupled with each other to give a product having a (CD 2)8 backbone, which lead to half-deuterated palmitic acid. Infrared reflection-absorption spectroscopy is being used in the laboratory of Professor Richard Mendelsohn, Rutgers University (Newark, NJ) to estimate the conformational order along the chain of fatty acids and diacylphospholipids. The synthesis outlined above lays the groundwork for this approach.;[1-13C]-Labeled fatty acids (C22:0, C24:0, and C26:0) were synthesized. The carboxyl 13C-labeled fatty acids are being used to study the binding of very long-chain fatty acids to albumin in the laboratory of Professor James A. Hamilton, Boston University School of Medicine (Boston, MA).;The chemical synthesis of plasmalogen was achieved. It started with isopropylidene- sn-glycerol, which was converted into 2,3-bis-O-(4 '-methoxybenzyl)-sn-glycerol. An O -alkynyl group was introduced at the sn-1 position in a one pot three-step reaction. Partial hydrogenation of the resulting O-alkynyl ether using Lindlar catalyst gave a cis O-alkenyl ether. The p-methoxybenzyl groups at the sn-2 and sn-3 positions were removed by Birch reduction to give 1-O-(1'-cis-alkenyl)- sn-glycerol which was converted into plasmalogen.;A similar strategy was used to prepare a plasmalogen analog with a methoxy group at the sn-2 position. This compound is also an analog of the antitumor ether lipid ET-18-OCH3. This analog was tested for antitumor properties in the laboratory of Professor Gilbert Arthur, University of Manitoba (Winnipeg, Manitoba, Canada). The analog is a potent inhibitor of the breast cancer cell line MCF-7.;Dequalinium (an antineoplastic drug) is active in various tumor systems. It is unclear where dequalinium binds to protein kinase C (PKC). Three unsaturated dequalinium analogs bearing a C10 linker were synthesized and tested against PKCalpha. The IC50 values of the cis, trans, and alkyne dequalinium analogs against PKCalpha (determined by Professor Susan A. Rotenberg, Queens College of CUNY), are: 52 +/- 12, 12 +/- 3, and >100 muM, respectively.
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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.