- Ether phospholipid-AZT conjugates possessing anti-HIV and antitumor cell activity. Synthesis, conformational analysis, and study of their thermal effects on membrane bilayers
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The 1-O-hexadecyl-2-O-methyl-sn-glyceryl phosphodiester AZT 4 and hexadecyl-phosphodiester AZT 5 derivatives were synthesized and found to be active against HIV-1, HIV-2, and tumor cell proliferation. Compared to AZT, compound 4 possessed ca. 10-fold lowe
- Mavromoustakos,Calogeropoulou,Koufaki,Kolocouris,Daliani,Demetzos,Meng,Makriyannis,Balzarini,De Clercq
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p. 1702 - 1709
(2007/10/03)
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- Modified ether glyceroglycolipids
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This invention provides lipids having: 1) a glycerol backbone; 2) a hydrocarbon chain, preferably saturated and containing 16 or 18 carbon atoms, attached to C-1 of the backbone by an ether linkage; 3) a methyl group attached to C-2 of the backbone, prefe
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- Synthesis and growth inhibitory properties of glycosides of 1-O- hexadecyl-2-O-methyl-sn-glycerol, analogs of the antitumor ether lipid ET- 18-OCH3 (edelfosine)
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Glycosylated antitumor ether lipids (GAELs), analogs of 1-O-octadecyl- 2-O-methyl-sn-glycero-3-phosphocholine (1, ET-18-OCH3, edelfosine), were synthesized in good overall yields by glycosylation of 1-O-alkyl-2-O- methyl-sn-glycerol and tested for in vitro antineoplastic activity against a variety of murine and human tumor cell lines. Stereospecific glycosylation was achieved by the use of 2-O-acetyl-3,4,6-tri-O-benzylglucopyranosyl and - mannopyranosyl trichloroacetimidates as donors, with trimethylsilyl trifluoromethanesulfonate as catalyst in the presence of molecular sieves at -78 °C. The GAELs differ from 1 in having the sn-3-phosphocholine residue replaced by one of the following monosaccharide residues: β- and α-2- deoxy-D-arabino-hexopyranosyl, α-D-mannopyranosyl, 2-O-methyl-β-D- glucopyranosyl, and 2-O-methyl-α-D-mannopyranosyl. 1-O-Hexadecyl-2-O- methyl-3-O-(2'-deoxy-β-D-arabino-hexopyranosyl)-sn-glycerol (2) was more effective than 1 in inhibiting the growth of MCF-7 (human breast cancer) and its adriamycin-resistant form MCF-7/adriamycin, and murine Lewis lung cancer cells. 2-Deoxy-β-D-arabino-hexopyranoside 2 was also an effective growth inhibitor of two drug-resistant leukemic cell lines, P388/Adr and L1210/vmdr.
- Marino-Albernas, José R.,Bittman, Robert,Peters, Andrew,Mayhew, Eric
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p. 3241 - 3247
(2007/10/03)
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- Regiospecific Opening of Glycidyl Derivatives Mediated by Boron Trifluoride. Asymmetric Synthesis of Ether-Linked Phospholipids
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A short, chiral synthesis of unnatural, cytotoxic ether-linked phospholipids is reported in which the key step is the very high regio- and stereospecific nucleophilic opening of the p-toluenesulfonate (1a, 1b) or tert-butyldiphenylsilyl ether (6a, 6b) derivatives of (R)- or (S)-glycidol with 1-hexadecanol using boron trifluoride etherate as catalyst.The enantiomeric excess of the ring-opened products was >94percent, as judged by 1H NMR and chiral HPLC analysis of the Mosher ester derivatives, indicating that ring opening of 1 and 6 proceeds without significant loss of optical purity.The synthetic strategy of using optically active glycidyl derivatives as the precursor of the glycerol backbone permits the desired enantiomers of 1(3)-O-2-O-methylphosphocholines (5a, 5b) to be generated in good yield and high optical purity from the ring-opened intermediates (2, 7) in three steps without the use of protecting groups.
- Guivisdalsky, Pedro N.,Bittman, Robert
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p. 4637 - 4642
(2007/10/02)
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- Stereospecific Synthesis of Ether and Thioether Phospholipids. The Use of L-Glyceric Acid as a Chiral Phospholipid Precursor
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A novel stereospecific synthesis of biologically active ether phospholipids is reported.The synthesis is based on (1) the use of L-glyceric acid as the chiral center for the construction of the optically active phospholipid molecule, (2) the introduction
- Bhatia, Suresh K.,Hajdu, Joseph
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p. 5034 - 5039
(2007/10/02)
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- A NEW APPROACH TO THE SYNTHESIS OF ETHER PHOSPHOLIPIDS. PREPARATION OF 1,2-DIALKYLGLYCEROPHOSPHORYLCHOLINES FROM L-GLYCERIC ACID
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A novel stereospecific synthesis of antitumor active ether phospholipids is reported.
- Bhatia, Suresh K.,Hajdu, Joseph
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p. 271 - 274
(2007/10/02)
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