Triester Derivatives Research Articles

Synthesis and Evaluation of Some Novel Phosphoramidate Derivatives of 3′-Azido-3′-Deoxythymidine (AZT) as Anti-HIV Compounds

A series of monophosphate triester derivatives of 3′-azido-3′-deoxythymidine (AZT), designed as membrane-soluble pro-drugs of the nucleotide (AZTMP), have been tested for activity against the human immunodeficiency virus (HIV-1). It has been found that when carboxyl-protected, amino-linked amino acids, and alkyl chains, are asymmetrically substituted on the 5′-phosphate a significant antiviral effect is observed. Moreover, the activity of the compounds is profoundly dependent on the structure of the phosphate moiety, and in particular on the nature of the amino acid.

SYNTHESIS OF SYMMETRICAL AND UNSYMMETRICAL TRIESTER PHOSPHITES

Abstract A method for one-pot synthesis of either symmetrical or unsymmetrical triester phosphites [(RO)3P or (RO)(R1O)2P, (RO)(R1O)(R2O)P and ROP R, R1, R2 = alkyl or phenyl] at room temperature is proposed. Hexaalkyltriamides of phosphorous acid and amidophosphite intermediates [P(N∗R2)3, and ROP(NR∗2)2, (RO)2PNR∗2, (RO)(R1O)PNR;; R∗2=CH3, C2H5], activated by imidazole and carbon disulfide, are used as new phosphorylating reagents. Six phosphite and thiophosphate triester derivatives of phenol, cis-9-octadecene-1-01, cholesterol, β-sitisterol, 1,3-butane diol and 1-nonanol have been synthesized in high final yields (85-94%).

Synthesis and biological evaluation of some phosphate triester derivatives of the anti-cancer drug araC.

A number of novel phosphate triester derivatives of the anti-cancer nucleoside analogue araC have been prepared by a rapid 2-step procedure, not necessitating prior sugar protection. Spectroscopic and lipophilicity data have been collected on these compounds. An in vitro assay indicated inhibition of thymidine incorporation by mammalian epithelial cells, by each of these compounds, in the range 3-300 microM. Moreover, the degree of inhibition showed a close correlation to chemical structure; in particular, there was a clear relationship between inhibition of thymidine incorporation and log(P). These results are consistent with cellular penetration by the intact phosphate triesters and intracellular action by an unspecified mechanism. Triethyl phosphate is inactive under the conditions of the test.

DETERMINATION OF DOMOIC ACID IN SHELLFISH

Domoic acid was extracted from mussels, clams or oysters with hot 0.1 N HCl. The extract was cooled, centrifuged and diluted for direct HPLC analysis. Confirmation after solid phase extraction cleanup of the extracts was carried out by HPLC of the phenylisothiocyanate (PlTC) derivative or the tri-isopropyl ester, by GC of the N-trifluoroacetyl (TFA) or N-t-butyldimethylsilyl triester derivative or by TLC. Detection limits were ca 1 μg/g by direct HPLC, 10μg/g by GC and 40 μg/g by TLC.

ChemInform Abstract: A General Procedure to Convert H‐Phosphonate Mono‐ or Diesters of Nucleic Acids into Valuable Phosphate Di‐ or Triesters.

Treatment of properly-protected d-nucleoside 3′-H-phosphonate mono- or diesters with N,O-bis(trimethylsilyl)acetamide, followed by the addition of an appropriate chloride, affords 3′-phosphate di- or triester derivatives, respectively.

A general procedure to convert H‐phosphonate mono‐ or diesters of nucleic acids into valuable phosphate di‐ or triesters

AbstractTreatment of properly‐protected d‐nucleoside 3′‐H‐phosphonate mono‐ or diesters with N,O‐bis(trimethylsilyl)acetamide, followed by the addition of an appropriate chloride, affords 3′‐phosphate di‐ or triester derivatives, respectively.

ChemInform Abstract: AN APPROACH TO THE SYNTHESIS OF LIPONUCLEOTIDES

AbstractPhosphorylierung des Thymidins (Ia) bzw. des Diacylglycerins (Va) mit dem Reagenz (II) gibt die Derivate (Ib) bzw. (Vb), die unmittelbar mit dem Alkohol (III) bzw. mit (Ia) umgesetzt werden.

An approach to the synthesis of liponucleotides

AbstractPhosphorylation of 3′‐O‐levulinoylthymidine*** using 2‐chlorophenyl bis‐O‐(1‐benzo‐triazolyl) phosphate, followed by addition of 1‐hexadecanol, afforded in high yield a fully protected triester derivative of thymidine.Similarly, phosphorylation of 1,2‐di‐O‐palmitoyl‐sn‐glycerol with the same reagent and subsequent addition of the above thymidine derivative gave a triester derivative of thymidine in excellent yield. Both triester derivatives were efficiently converted into the corresponding liponucleotides by the removal of the 2‐chlorophenyl and levulinoyl protective groups.

Stimulated sequential dehydroxy-fluorination: a safe, convenient method for gas chromatographic analysis of phosphate diesters with possible application to hydrolysates of organophosphorus pesticides and nerve gases

Model studies with di- n-butylphosphate show that organic triester derivatives chosen to gain increased volatility by simply minimizing total molecular weight are relatively poorer in gas chromatographic properties than the diesterphosphoro-fluoridate analogue because both the molecular weight and the overall polarity of the derivative are critical factors. We find the substitution of the hydroxyl group by fluorine is the most successful way at present to derivative phosphate diesters. Fluorine substitution is effective because it reduces the strong phosphoryl dipole, presumably by decreasing the electron density on the oxygen atom via pπ-pπ back-bonding to the phosphorus. Dehydroxy-fluorination is best carried-out by a sequential reagent process starting with dicyclohexylcarbodiimide to stimulate and direct the dehydroxy-step before adding hydrogen fluoride as the active fluorinating agent. This procedure is safe and convenient and is believed applicable to a wide range of hydroxy-phosphates including the hydrolysates of many organophosphorus pesticides and nerve gases at minimal sample sizes.

Characterization and mass spectral analysis of some grayanotoxin derivatives.

The mass spectra of grayanotoxin III and some of its mono-, di, and tri-ester derivatives are discussed. Some of the physiological responses of this compound class are also presented. The extraction of this material from a natural source is discussed as well as the schemes for ester derivatization and spectral characterization of all compounds studied. High resolution mass spectral analysis and comparison of the mass spectra of similar compounds were used to define possible fragmentation mechanisms.

Fractionation and identification of milk polar lipids: Triester glycophospholipids

A representative sample of the polar lipids of milk was isolated in a preparative scale from commercially spray dried milk using mild isolation procedures. By silicic acid chromatography at least 16 peaks of phospholipids (mainly glycophospholipids), two peaks of cerebrosides, and three peaks of ganglioside-like mucolipids were identified. Strong evidence is presented supporting the view that the glycophospholipids are phosphate triester derivatives, for which general formulae are tentatively proposed. At a first approximation, the composition of the polar lipids of milk is the following: cerebrosides, 8.8; polyglycerophosphatides, 1.6; phosphatidylethanolamine, 13.6; galactophosphatidylethanolamine or phosphatidylethanolamine plasmalogen, 4.0; galactophosphatidylserine, 10.5; inositolphosphatides, 11.9; other “glycocephalins”, 2.2; phosphatidylcholine, 9.1; galactophosphatidylcholine, 8.7; lactophosphatidylcholine, 8.9; other “lecithins”, 5.0; sphingomyelins, 5.2; galactosphingomyelin, 4.6; glucomannosphingomyelin, 3.5; other “sphingomyelins”, 11.3, all expressed in moles/100 moles of lipid phosphorus. The presence of glyceryl ether phospholipids in milk is also shown and their function discussed. It is suggested that all the glyceryl ether lipids of milk are found in the phospholipid fraction. The idea that new, unknown lipids, containing spermine or other similar bases, are probably present in milk is discussed. A large proportion of milk lipids was found in the form of proteolipids. New properties for proteolipids are deduced, and an attempt to explain their linkages between lipid and peptide, as well as the role of heavy metals in their formation is made.