Inhibiting effect of 6-methyluracil derivatives on the free -radical oxidation of 1,4-dioxane

The antioxidation activity of 5-substituted 6-methyluracils was quantitatively estimated in the model system of initiated radical-chain oxidation of 1,4-dioxane. The rate constants of the reactions of 1,4-dioxane peroxide radicals with 6-methyluracil (1), 6-methyl-5-piperidinouracil (2), 6-methyl-5-morpholinomethyluracil (3), 6-methyl-5-morpholinouracil (4), 6-methyl-5-methylaminouracil (5), 5-ethylamino-6-methyluracil (6), and 5-hydroxy-6-methyluracil (7) were measured. Among compounds 1–7, derivative 7 is most efficient with an inhibition rate constant of (5.2±0.1) · 10⁴ L mol^-1 s^-1 (60 °C).     

Experimental and quantum-chemical study of the mechanism of oxidation of 5-hydroxy-6-methyl-uracil by molecular oxygen in the presence of copper(II) ions

It has been discovered experimentally that 5,5,6-trihydroxy-6-methylpyrimidine-2,4-dione is formed on oxidizing 5-hydroxy-6-methyluracil with molecular oxygen in aqueous medium in the presence of copper(II) chloride. Ab initio and DFT calculations on the 6-31G* basis, both in the gas phase and allowing for solvent, showed that the process proceeds with the direct participation of an activated oxygen molecule on the complex CuCl₂·(5-hydroxy-6-methyluracil)2. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 586-593, April, 2009.     

Oxidation of 5-hydroxy-6-methyluracil with molecular oxygen in the presence of copper(II) chloride in aqueous solution

Oxidation of 5-hydroxy-6-methyluracil with molecular oxygen in the presence of copper(II) chloride involves formation of a 2 : 1 complex with copper(II). The rates of consumption of initial 5-hydroxy-6-methyluracil and oxygen were determined in the temperature range from 40 to 80°C. A probable reaction mechanism implies fixation and activation of molecular oxygen on the copper(II) complex with 5-hydroxy-6-methyluracil with formation of active oxygen species that are responsible for hydroxylation of the double C⁵=C⁶ bond in the uracil molecule.     

5-Hydroxy-6-methyluracil as an efficient scavenger of peroxy radicals

The reaction of 5-hydroxy-6-methyluracil with peroxy radicals generated by the thermal decomposition of azodiisobutyronitrile was studied at 75 °C in ethanol, propan-2-ol, and dimethyl sulfoxide. The stoichiometry of the reaction is 1: 1. The reaction product is dihydro-6-hydroxy-6-methylpyrimidine-2,4,5-trione in an anhydrous solvent or dihydro-5,5,6-trihy-droxy-6-methylpyrimidine-2,4-dione in the presence of water. The rate constant for the reaction of 5-hydroxy-6-methyluracil with the peroxy radicals is ∼10⁸ L mol⁻¹ s⁻¹.     

Electrophilic ipso-substitution in uracil derivatives

Treatment of 5-iodo-1,3,6-trimethyluracil with 50% H₂SO₄ gives 1,3,6-trimethyluracil; with 5-bromo-1,3,6-trimethyluracil, a mixture of 1,3,6-trimethyluracil and 6-bromomethyl-1,3-dimethyluracil is obtained. 5-Chloro-1,3,6-trimethyluracil remains inert under these conditions. According to the DFT modeling of the reactions of 5-halo-1,3,6-trimethyluracils, a nucleophilic agent can abstract either Hal⁺ or the methyl proton from the carbocation formed by protonation of the starting halouracil at position 5, which accounts for the formation of two products from the 5-bromo derivative. Under similar conditions, 6-methyluracil dibromohydrin yields N-bromo-5-bromo-6-hydroxymethyluracil. Bromination or chlorination of 5-hydroxymethyl- or 5-formyl-6-methyluracils follows the ipso-substitution scheme leading to 6-methyluracil 5-halo- and 5,5-dihalohydrins.     

Synthetic approach toward antibiotic tunicamycins — VI total synthesis of tunicamycins

Tunicamycins and their eight analogs have been synthesized by condensation of a N-acetyl-D-glucosamine derivative and an anomeric chloride of tunicaminyl uracil, followed by deprotections and N-acylation.     

1, 4-取代-2-丁炔共二聚反应中溶剂效应和盐效应对反应选择性的影响

PdCl~2(PhCN)~2催化的1, 4-取代-2-丁炔与烯丙基氯的共二聚反应中, 考察了不同的溶剂、不同的盐组分对生成双键的顺反异构体的影响。实验结果发现, 1, 4-二氯-2-丁炔与烯丙基氯的反应中, 不加溶剂和氯化物, 产物的双键以E式为主, 加入溶剂和氯化物, 产物以Z式为主。     

Purification of long-chain fatty acid ester of epigallocatechin-3-O-gallate by high-speed counter-current chromatography

Epigallocatechin-3-O-gallate (EGCG) was modified by catalytic esterification with hexadecanoyl chloride. A long-chain fatty acid ester derivative was obtained from the purification of this reaction product by high-speedcounter-current chromatography using a solvent system composed of n-hexane-ethyl acetate-methanol-water (1:1:1:1, v/v). The structure of the derivative, epigallocatechin-3-O-gallate-4'-hexadecanate, was elucidated by IR, MS and 1H NMR.     

The Benzoylation of 6-Methyluracil and 5-Nitro-6-methyluracil

6-Methyluracil and 5-nitro-6-methyluracil react with variable molar quantities of benzoyl chloride in acetonitrile-pyridine at room temperature to give I-N, 3-N-dibenzoyl-6-methyluracil 3b and l-N-benzoyl-5-nitro-6-methyluracil 4b. The reactive rates of debenzoylation of 3b and 4b were investigated.     

HIV-1 RT抑制剂研究I.1,3-二苄基-6-(3,4-环氧丁基)尿嘧啶的合成

报道了1,3-二苄基-6-(3,4-环氧丁基)尿嘧啶的合成新方法.以6-甲基尿嘧啶(1)为起始物,经1,3-二苄基-6-甲基尿嘧啶(2)及未见文献报道的1,3-二苄基-6-(3-丁烯基)尿嘧啶(3)和1,3-二苄基-6-(3-羟基-4-溴丁基)尿嘧啶(4),首次高收率合成了1,3-二苄基-6-(3,4-环氧丁基)尿嘧啶(5),并对其化学结构进行了表征.     

The synthesis and properties of certain N-methylated 5-diazouracils

The reduction of 1-methyl-, 3-methyl- and 1,3-dimethyl-5-nitrouracil (Ia-c) to the corresponding 5-aminouracils (IIa-c) is described. Diazotization of 5-amino-1-methyluracil (IIa) and 5-amino-1,3-dimethyluracil (IIc) gave 5-diazouracils which were characterized as thermally stable C6 covalent hydrates (III and XIII). Diazotization of 5-amino-3-methyluracil (IIb) gave anhydro 5-diazo-3-methyluracil (X) which underwent covalent methanolation and thermally reversible covalent hydration. Treatment of III and XIII with hot methanol resulted in solvent exchange of the C6 hydroxyl groups by a mechanism which may involve initial formation of diazoethers. Treatment of the methanolates (IV, XI and XIV) with dimethylamine resulted in coupling at the diazo group with a concomitant expulsion of the C6 methoxyl groups to give 5-(3,3-dimethyl-1-triazeno)uracils (XVa-c).     

Mild and Useful Method for N-Acylation of Amines

Iodine is found to promote quantitative N-acylation of primary and secondary amines (aliphatic and aromatic) in a very short time with an equimolar amount of acetyl chloride and benzoyl chloride under solvent-free conditions at room temperature. This catalytic acylation of amines offers an additional useful method for the acetylation using acetyl chloride instead of acetic anhydride and other acetylating agents. This method is also useful in the N-acylation of heterocycles. Mild reaction condition, high selectivity, efficiency, and good yields are some of the major advantages of the procedure.     

One-pot preparation of Oxazol-5(4H)-ones from amino acids in aqueous solvents

A method for one-pot synthesis of oxazol-5(4H)-ones has been developed using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM), which is available for the activation of carboxylic acids in an aqueous solvent. The oxazolones were prepared by the N-acylation of amino acids with carboxylic acids and the subsequent cyclodehydration of the resulting N-acylamino acids by the addition of N,N-diethylaniline. Since both these reactions proceed effectively with the same coupling reagent, DMT-MM, in aqueous solvents, the procedure is simplified and becomes easy to perform. In addition, 5-(triazinyloxy)oxazole derivatives have been synthesized by controlling the basicity of the reaction system.     

Kinetic resolution of primary amines via enantioselective N-acylation with acyl chlorides in the presence of supramolecular cyclodextrin nanocapsules

The non-enzymatic kinetic resolution of primary amines via enantioselective N-acylation with acyl chlorides was accomplished for the first time by using the selective sequestration of one enantiomer within a supramolecular cyclodextrin (CD) nanocapsule in nonpolar solvents. In addition, the first example of a crystalline structure for an inclusion complex between an acyl chloride and a CD derivative is reported.     

The regioselectivity of dibutylstannylene-mediated oxidation of methyl 3',4'-O-isopropylidene-α- and β-lactoside. A new synthesis of n -acetylllactosamine

The dibutylstannylene-mediated oxidation of methyl 3',4'-O-isopropylidene-a-lactoside (1) under different conditions using bromine as oxidizing agent has been investigated. The regioselectivity of this reaction strongly depends on the solvent and the nature of the added base. The 2-keto derivative, isolated as the corresponding methyloximino (10) or benzyloximino (13) derivatives, is the only oxidation product when acetonitrile is used as solvent and tributyltin methoxide as base. The oxidation of methyl 3',4'- O -isopropylldene-β-lactoside (5) under the same conditions results in regioselective oxidation at C-3. The simple regiosetective oxidation of the α-anomer (1) leads, after hydrogenation of the oximes (10 and 13) derived from the resulting 2-keto derivative, to lactosamine derivatives in a simple and convenient manner.     

New acetenyl acyclic nucleosides synthesis of 1-(propargyloxymethyl) derivatives of uracil

Alkylation of trimethylsilyl derivatives of uracil, thymine, 5-fluorouracil, and 6-methyluracil with propargyloxymethyl chloride afforded the corresponding 1-(propargyloxymethyl) derivatives, new unsaturated acyclic nucleosides having an end carbon-carbon triple bond.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 797–799, June, 1993.     

1,3-二(乙氧基甲基)-5-N,N-二甲氨基-6-甲基尿嘧啶的合成

报道了1,3-二(乙氧基甲基)-5-N,N-二甲氨基-6-甲基尿嘧啶方便、高产率的合成方法. 以6-甲基尿嘧啶(1)为起始物, 经硝化、嘧啶N¹,N ³-烷基化、还原及氨基甲基化, 首次高产率合成了1,3-二(乙氧基甲基)-5- N,N -二甲氨基-6-甲基尿嘧啶(5), 并对其化学结构进行了表征.     

An unexpected rearrangement during mitsunobu epimerization reaction of sugar derivatives

Mitsunobu reaction on the glucose derivative (3S,4R,5R,6R)-3,4,5, 7-tetrabenzyloxy-6-hydroxy-1-heptene yielded an unexpected rearrangement major product. Its structure was determined as (3R,4R, 5R,6S)-4,5,6,7-tetrabenzyloxy-3-hydroxy-1-heptene. The suggested rearrangement mechanism involves an initial intramolecular cyclization, followed by ring opening by the nucleophile p-nitrobenzoate. Product distribution of the Mitsunobu reaction was substrate-dependent, with the corresponding mannose derivative (the 3R epimer) giving less of the initial intramolecular reaction products and the corresponding galactose derivative (the 5S epimer) yielding almost exclusively the expected epimerization product. Varying the Mitsunobu reaction conditions (addition of base and using nonpolar solvent) led to the expected epimerization product of the glucose derivative.     

Reaction of acridine with pyrazolone derivatives

A mixture of acridine and a pyrazolone derivative was reacted in the solid state (without solvent). It is proposed that the enol tautomer (the C4‐position) of the pyrazolone derivative attacks the C9‐position of acridine through a nucleophilic reaction resulting in products where the C4‐position of pyrazolone is connected to the C9‐position of acridine. When the reaction of 3‐methyl‐1‐phenyl‐5‐pyrazolone and acridine was carried out at low temperature (25°–50°), the reaction product was obtained even when the majority of the reaction mixture had not melted. The same reaction was also carried out in the presence of an ultrasonic wave at same temperature (25°–50°) and the reaction product was obtained in high yield. Under ultrasonic conditions, the reaction mixture was not melted. However, the interface between 3‐methyl‐1‐phenyl‐5‐pyrazolone and acridine gradually changed from white to black. In this reaction, the dihydroacridine dimer is not obtained.     

Bromo derivatives of 1-(4-hydroxyphenyl)dihydrouracil and 1-(4-hydroxyphenyl)-5- or -6-metehyldihydrouracils

Bromination of 1-(4-hydroxyphenyl)dihydrouracil and its 6-methyl derivative with bromine in refluxing acetic acid gave 1-(3,5-dibromo-4-hydroxyphenyl)-5-bromo-, 1-(3,5-dibromo-4-hydroxyphenyl)-5-bromo-, and 1-(3,5-dibromo-4-hydroxyphenyl)-5-bromo-6-methyldihydrouracils and 1-(3,5-dibromo-4-hydroxyphenyl)-5-methyluracil. 5-Bromo- and 5,5-dibromodihydrouracils were dehydrobrominated, and the same compounds undergo decomposition to 3,5-dibromo-4-hydroxyphenylurea upon alkaline hydrolysis.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1251–1254, September, 1982.