Synthesis of chiral diester- and ester/ether-phosphatidylcholines. Calorimetric studies of asymmetric-chain phosphatidylcholines in liposomes.
Item
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Title
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Synthesis of chiral diester- and ester/ether-phosphatidylcholines. Calorimetric studies of asymmetric-chain phosphatidylcholines in liposomes.
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Identifier
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AAI9009709
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identifier
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9009709
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Creator
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Ali, Shaukat.
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Contributor
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Adviser: Robert Bittman
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Date
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1989
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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 | Chemistry, Biochemistry | Biophysics, General
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Abstract
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Diester- and ester/ether-phosphatidylcholines (PCs) have been prepared from (R)-glycidyl tosylate in good yields. The key step in the synthesis of 1,2-distearoyl-sn-glycero-3-PC was the ring opening of the epoxide with stearic anhydride (1.5 equiv) and BF{dollar}\sb3\cdot{dollar}Et{dollar}\sb2{dollar}O as a catalyst. The resulting 1,2-diacyl-sn-glycerol 3-tosylate was obtained in a one-pot synthetic procedure in good yield (76%). The tosylate group was converted into the phosphocholine moiety by using standard procedures. The key step in the synthesis of ester/ether-PC was the BF{dollar}\sb3\cdot{dollar}Et{dollar}\sb2{dollar}O-mediated ring opening of glycidyl tosylate with benzyl alcohol as a nucleophile to give the ring-opened product in good yield (84%) and in high optical purity ({dollar}\sim{dollar}96% enantiomeric excess).;The CdCl{dollar}\sb2{dollar}-complex of glycero-sn-3-phosphocholine has been used to prepare a 1,2-di (5{dollar}\sp\prime R/S, 9\sp\prime R, 13\sp\prime R){dollar}-{dollar} 5\sp\prime {dollar},9{dollar}\sp\prime{dollar},13{dollar}\sp\prime {dollar},17{dollar}\sp\prime {dollar}-tetramethyloctadecanoyl) -sn-glycero-3-PC (di-C{dollar}\sb{lcub}22{rcub}{dollar}-chain PC). High-resolution differential scanning calorimetric (DSC) studies of the di-C{dollar}\sb{lcub}22{rcub}{dollar}-chain PC and a highly asymmetric-chain PC having a di-C{dollar}\sb{lcub}22{rcub}{dollar}-chain at the sn-1 position and a C{dollar}\sb{10}{dollar}-chain at the sn-2 position did not show any phase transition temperature between {dollar}-{dollar}28{dollar}\sp\circ{dollar} and 68{dollar}\sp\circ{dollar}C.;Asymmetric-chain PCs (1-octadecanoyl-2-decanoyl-sn-3-glycerophosphocholines (C18:C10PC)) modified in the choline moiety have been prepared in four steps by using a semisynthetic approach. The mixed-chain PC was hydrolyzed with phospholipase D (Streptomyces chromofuscus) to give the corresponding phosphatidic acid, which was coupled with different aminoalkanols giving the asymmetric-chain phospholipids modified in the polar head group.;Liposomes were prepared from mixtures of C18:C10PC and a symmetric-chain PCs having {dollar}\omega{dollar}-CH{dollar}\sb2{dollar}=CH, {dollar}\omega{dollar}-{dollar}\rm CH\sb3 CO\sb2{dollar}, and {dollar}\omega{dollar}-{dollar}\rm CH\sb3 CO{dollar} moieties.;The effects of the {dollar}\omega{dollar}-{dollar}\rm CH\sb3 CO\sb2{dollar} and {dollar}\omega{dollar}-{dollar}\rm CH\sb3 CO{dollar} groups of C18:C(10:{dollar}\omega{dollar}-{dollar}\rm CH\sb3 CO\sb2{dollar})- and C18:C(10:{dollar}\omega{dollar}-{dollar}\rm CH\sb3 CO{dollar})PCs on the mixing behavior in the liposomes of C18:C10PC were studied by DSC. Phase diagrams for the binary systems C18:C10PC/C18:C(10:{dollar}\omega{dollar}-{dollar}\rm CH\sb3 CO\sb2{dollar})PC and C18:C10PC/C18:C(10:{dollar}\omega{dollar}-{dollar}\rm CH\sb3 CO{dollar})PC were constructed based on the calorimetric data. Although PCs with {dollar}\omega{dollar}-{dollar}\rm CH\sb3 CO\sb2{dollar} and {dollar}\omega{dollar}-{dollar}\rm CH\sb3 CO{dollar} moieties show almost a similar trend on the gel phase immiscibility at low temperatures, the effect is more pronounced in the PC having a {dollar}\omega{dollar}-{dollar}\rm CH\sb3 CO{dollar} moiety. The mixing is near-ideal for both the binary systems in the liquid-crystalline state. (Abstract shortened with permission of author.).
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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.
