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  • 1
    ISSN: 1573-4986
    Keywords: Glycoside ; synthesis ; cancer ; hexamethylmelamine ; methylol ; formaldehyde ; modelling ; deacetylation ; triazine ; N-hydroxymethyl
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The synthesis of analogues of the anti-tumour drug 2-[N-(hydroxymethyl)methylamino]-4,6-bis (dimethylamino)-1,3,5-triazine (HMPMM) in which the OH or a dimethylamino group is replaced by a carbohydrate has been explored. Triazinyl β-glycosides were readily prepared by reaction of sugars with trimethyl-triazinylammonium salts. These were made with one or two methylamino groups on the triazine for reaction with formaldehyde to give the cytotoxic NMeCH2OH group. However, reaction of the triazinyl glycosides with formaldehyde gave complex intractable mixtures. When the carbohydrate portion was changed to the fully protected 2,3,4,6-tetra-O-acetyl glucose a good yield of the 2-[N-(hydroxymethyl)methylamino]-4-(dimethylamino)-1,3,5-triazin-2-yl tetra-O-acetyl β-glucoside was obtained. However, de-acetylation using sodium methoxide also removed the N–CH2OH group. We are investigating protection of the base-sensitive N–CH2OH group as trialkylsilyl and benzyl ethers and are looking at de-acetylation methods that are more selective. We have prepared glycosides in which the sugar is joined through the oxygen of the NMeCH2OH group. Coupling of acetobromoglucose with HMPMM catalysed by silver salts was not successful. Although methyl and cyclohexyl derivatives of HMPMM may be produced in high yields by reaction of HMPMM with methyl and cyclohexyl alcohols under acidic catalysis, production of glycosides in this way gave poor yields. MNDO calculations on reactions of HMPMM helped us devise improved reaction conditions for the condensation of 2,3,4,6-tetra-O-acetyl glucose with HMPMM and its derivatives. The best procedure to generate one of the target glycosides is to react 2,3,4,6-tetra-O-acetyl glucose and formaldehyde with 2-methylamino- 4,6-bis(dimethylamino)-1,3,5-triazine. The β-glycoside product was de-acetylated using potassium carbonate in dry methanol. Abbreviations: HMM, hexamethylmelamine (2) or 2,4,6-tris(dimethylamino)-1,3,5-triazine; HMPMM, hydroxymethylpentamethylmelamine or 2-[N-(hydroxymethyl)-methylamino]-4,6-bis(dimethylamino)-1,3,5-triazine; PMM, Pentamethylmelamine or 2-methylamino-4,6-bis(dimethylamino)-1,3,5-triazine; TBMS, t-Butyldimethylsilyl; p-TSA, p-Toluenesulphonic acid
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 0192-8651
    Keywords: Computational Chemistry and Molecular Modeling ; Biochemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Computer Science
    Notes: Ab initio calculations employing a standard double-zeta basis set augmented with various polarization functions have been used to investigate the lowest energy region of the ground-state potential energy surface of the formamide molecule. Hartree-Fock calculations with only d polarization functions on the nonhydrogen atoms located two stable minima, that with geometry distorted from planarity having slightly lower energy; only one stable minimum with planar structure is found when p polarization functions on the hydrogens are included. In contrast optimizations, which account approximately for the correlation energy using second-order Møller-Plesset perturbation theory consistently favor a single slightly nonplanar minimum energy geometry.
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1520-4804
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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