Synthesis of 5-Phenylcytosine Nucleoside Derivatives

1996 ◽  
Vol 61 (4) ◽  
pp. 645-655 ◽  
Author(s):  
Marcela Krečmerová ◽  
Hubert Hřebabecký ◽  
Antonín Holý
Keyword(s):  
Acetic Anhydride ◽  
Thionyl Chloride ◽  
Alkaline Hydrolysis ◽  
Hydrogen Bromide ◽  
Analogous Reaction ◽  
Final Reaction Product ◽  
Cyclic Sulfite ◽  
Higher Temperature ◽  
Hydrolysis Of ◽  
Tin Tetrachloride

Reaction of silylated 5-phenylcytosine with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribose, catalyzed with tin tetrachloride, and subsequent methanolysis afforded 5-phenylcytidine (2). This compound reacted with thionyl chloride in acetonitrile to give cyclic sulfite 3 which on heating in dimethylformamide was converted into 2,2'-anhydro-1-(β-D-arabinofuranosyl)-5-phenylcytosine (4). Analogous reaction of compound 2 with thionyl chloride at reflux gave 5'-chloro-5'-deoxy-2',3'-cyclic sulfite 5. Its heating in dimethylformamide afforded 5'-chloro-2,2'-anhydro derivative 6, mild alkaline hydrolysis led to 5'-chloro-5'-deoxy-5-phenylcytidine (7). Alkaline hydrolysis of 5-phenyl-2,2'-anhydrocytidine (4) gave 5-phenylcytosine arabinoside 8, whereas the 2,2'-anhydro derivative 6 afforded 1-(5-chloro-5-deoxy-β-D-arabinofuranosyl)-5-phenylcytosine (11). At higher temperature, the final reaction product was 2,5'-anhydro-5-phenylcytidine (12). 5'-Chloro-5'-deoxynucleosides 7 and 11 reacted with tri-n-butyl- stannane to give 5'-deoxyribofuranosyl and 5'-deoxyarabinofuranosyl derivatives 15 and 16. 5-Phenylcytidine (2) was converted into the N4-acetate 17 with acetic anhydride. Further reaction with acetic anhydride and hydrogen bromide in acetic acid afforded a mixture of peracetylated 2'-bromo and 3'-bromo derivatives 18 and 19. Reaction with Zn/Cu couple gave 5'-O-acetyl-5-phenyl-2',3'-didehydro derivative 20 and 2',3',5'-tri-O-acetyl-5-phenylcytidine (21). Compound 20 was deblocked to 1-(2,3-dideoxy-β-D-glycero-pent-2-enofuranosyl)-5-phenylcytosine (22). Catalytic hydrogenation of compound 20 over palladium and subsequent deblocking of the protected 2',3'-dideoxy derivative 23 gave 1-(2,3-dideoxy-β-D-glycero-pentofuranosyl)-5-phenylcytosine (24).

Preparation of 5-Benzyluracil and 5-Benzylcytosine Nucleosides as Potential Inhibitors of Uridine Phosphorylase

1996 ◽  
Vol 61 (4) ◽  
pp. 627-644 ◽  
Author(s):  
Marcela Krečmerová ◽  
Hubert Hřebabecký ◽  
Antonín Holý
Keyword(s):  
Methyl Iodide ◽  
Thionyl Chloride ◽  
Alkaline Hydrolysis ◽  
Room Temperature ◽  
Silver Oxide ◽  
Uridine Phosphorylase ◽  
Cyclic Sulfite ◽  
Potential Inhibitors ◽  
Hydrolysis Of ◽  
Tin Tetrachloride

Reaction of 3,4,6-tri-O-acetyl-2-deoxyglucopyranosyl bromide (1) with silylated 5-benzyluracil and subsequent ammonolysis afforded α- and β-anomers of 5-benzyl-1-(2-deoxy-D-glucopyranosyl)uracil (2 and 3). Under catalysis with tin tetrachloride, silylated 5-benzyluracil reacted with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose to give 2',3',5'-tri-O-benzoyl-5-benzyluridine (10), which was converted into the 4-thio derivative 11 by reaction with Lawesson reagent. Debenzoylation of compound 11 afforded 5-benzyl-4-thiouridine (12), whereas its reaction with methyl iodide and deblocking gave 4-methylthiopyrimidine nucleoside 14. Amonolysis of derivative 12 at elevated temperature afforded 5-benzylcytidine (15). This reacted with thionyl chloride at room temperature to give cyclic sulfite 16 which on heating at 100 °C in dimethylformamide was converted into 5-benzyl-2,2'-cyclocytidine (17). Mild alkaline hydrolysis of compound 17 afforded 1-(β-D-arabinofuranosyl)-5-benzylcytosine (18). With boiling thionyl chloride, compound 15 formed 2',3'-cyclic sulfite 19 which on alkaline hydrolysis gave 5-benzyl-5'-chloro-5'-deoxycytidine (20). Compound 20 was reduced with tributylstannane to 5-benzyl-5'-deoxycytidine (21). Reaction of silylated 5-benzyluracil with 2-deoxy-3,5-bis(O-p-toluoyl)-D-ribofuranosyl chloride, catalyzed with mercury(II) bromide, afforded 5-benzyl-2'-deoxy-3',5'-bis(O-p-toluoyl)uridine (22) and its α-anomer 23. With Lawesson reagent, compound 22 gave 5-benzyl-4-thiouracil derivative 24 which was ammonolyzed to give 5-benzyl-2'-deoxycytidine (25). Analogously, compound 23 was converted into 5-benzyl-2-deoxy-α-cytidine (27). 5'-O-Benzoyl-5-benzyluridine (29) was converted into the 2,2'-anhydro derivative 30 which on reaction with hydrogen chloride afforded 3'-chloro-3'-deoxynucleoside 31. This compound was reduced with tributylstannane and the obtained 2'-deoxynucleoside 32 on treatment with thionyl chloride gave a mixture of erythro- and threo-3'-chloro-2',3'-dideoxynucleosides (33 and 34, respectively) which were reduced to 5'-O-benzoyl-5-benzyl-2',3'-dideoxyuridine (35). Compound 35 reacted with Lawesson reagent under formation of 4-thiouracil derivative 36 and this was deblocked to 5-benzyl-4-thio-2',3'-dideoxyuridine (37). On heating with ammonia, compound 37 was converted into 5-benzyl-2',3'-dideoxycytidine (38). Reaction of 4-thiouracil derivative with methyl iodide and subsequent hydrazinolysis afforded 4-hydrazino derivative 40 which was heated with silver oxide in ethanol to give a mixture of anomeric 5-benzyl-1-(2,3-dideoxyribofuranosyl)-2(1H)-pyrimidinones (42).

Synthesis and Reactions of Furo[3,2-b]pyrrole Type Aldehydes

1993 ◽  
Vol 58 (9) ◽  
pp. 2139-2149 ◽  
Author(s):  
Alžbeta Krutošíková ◽  
Miloslava Dandárová ◽  
Juraj Alföldi
Keyword(s):  
Acetic Anhydride ◽  
Ammonium Chloride ◽  
Alkaline Hydrolysis ◽  
Sodium Azide ◽  
Nmr Spectra ◽  
Hydrolysis Of ◽  
C Nmr

The synthesis of ethyl 2-formyl-4-benzylfuro[3,2-b]pyrrole-5-carboxylate (I) is described. A series of furo[3,2-b]pyrrole-2-carbaldehyde 2,6-dialkylphenylhydrazones (IIa - IIg) and dimethylhydrazones (IIIa - IIId) were prepared. By reaction of title compounds with hydroxylammonium chloride in acetic anhydride in the presence of pyridine corresponding cyano-substituted compounds (IVa - IVd) were obtained. Alkaline hydrolysis of IVa - IVd gave Va - Vb and the reaction with sodium azide and ammonium chloride in dimethylformamide led to VIa - VId. the structure of the compounds have been proved by UV, IR, 1H and 13C NMR spectra.

Synthesis of Novel 4-Amino-5-(disubstituted amino)-2-phenyl-2H-pyridazin-3-ones

1997 ◽  
Vol 62 (5) ◽  
pp. 800-808 ◽  
Author(s):  
Václav Konečný ◽  
Jozefína Žúžiová ◽  
Štefan Kováč ◽  
Tibor Liptaj
Keyword(s):  
Acetic Anhydride ◽  
Alkaline Hydrolysis ◽  
Acetyl Chloride ◽  
Cyclic Amines ◽  
Hydrolysis Of

Substituted 4-amino-2-phenyl-2H-pyridazin-3-ones 5a-5j have been prepared from 4-amino-5-chloro-2-phenyl-2H-pyridazin-3-one 1 which on reactions with acetyl chloride or acetic anhydride gives 4-acetylamino derivative 2 or 4-diacetylamino derivative 3, respectively. Derivatives 2 and 3 with dialkylamines and cyclic amines yielded appropriate 4-acetylamino-5-(disubstituted amino)-2-phenyl-2H-pyridazin-3-ones 4a-4j. Subsequent alkaline hydrolysis of the acetylamino derivatives 4a-4j let to the title compounds 5a-5j, which were screened for pesticidal activity, but none of them reached activity of the used standards.

Potential Nootropic Agents: Synthesis of Some 1,4-Disubstituted 2-Oxopyrrolidines and Some Related Compounds

1994 ◽  
Vol 59 (5) ◽  
pp. 1126-1136 ◽  
Author(s):  
Vladimír Valenta ◽  
Jiří Urban ◽  
Jan Taimr ◽  
Zdeněk Polívka
Keyword(s):  
Carboxylic Acid ◽  
Dicarboxylic Acid ◽  
Itaconic Acid ◽  
Thionyl Chloride ◽  
Alkaline Hydrolysis ◽  
Nootropic Activity ◽  
Carbonyl Chloride ◽  
Nootropic Agents ◽  
Hydrolysis Of ◽  
Related Compounds

4-(Aminomethyl)-1-benzyl-2-oxopyrrolidine (VI) was transformed by treatment with (4-benzhydrylpiperazin-1-yl)carbonyl chlorides IIIb - IIId and with (4-methylpiperazin-1-yl)carbonyl chloride (IIIa) to the carboxamides IVa - IVd. Heating of 1-(ethoxycarbonylmethyl)-2,4-dioxopyrrolidine (XIX) in acetonitrile in the presence of water afforded XVIIIa. Treatment with ammonia led to the diamide XVIIIc, while alkaline hydrolysis of XVIIIa gave the dicarboxylic acid XVIIIb. 4-(Aminomethyl)-1-(4-methylthiobenzyl)-2-oxopyrrolidine (XII) was prepared by the reaction of 4-(methylthio)benzylamine with itaconic acid and the following sequence of reactions starting from the obtained carboxylic acid VII including esterification, reduction and treatment the obtained alcohol IX with thionyl chloride, synthesis of phthalimido derivative XI and hydrazinolysis. Amine XII added to 4-chlorophenyl isocyanate formed XIII. The compounds prepared were tested for nootropic activity.

Studies on the Lignin of Eucalyptus regnans. III. The Isolation of an Alkali Lignin from Sulphate Pulping

1949 ◽  
Vol 2 (1) ◽  
pp. 117
Author(s):  
JWT Merewether
Keyword(s):  
Acetic Anhydride ◽  
Alkaline Hydrolysis ◽  
Empirical Formula ◽  
Benzoyl Chloride ◽  
Dimethyl Sulphate ◽  
Hydroxyl Groups ◽  
Equivalent Weight ◽  
Eucalyptus Regnans ◽  
Alkali Lignin ◽  
Hydrolysis Of

An alkali lignin containing no sulphur has been obtained as a by-product from the sulphate pulping of Eucalyptus regnans. Like other alkali lignins it contains hydroxyl groups, both acidic and alcoholic, as well as methoxyl groups. Acetic anhydride in pyridine yields an octoacetyl derivative which is readily hydrolysed by boiling water to a heptacetyl derivative. In pyridine, benzoyl chloride yields an octobenzoyl derivative while in aqueous alkali it yields a hexabenzoyl compound. Dimethyl sulphate yields a heptamethyl alkali lignin, diazomethane a hexamethyl derivative, while cold alkaline hydrolysis of the latter gives a pentamethyl derivative, and hot alkaline hydrolysis yields an anhydrotrimethyl alkali lignin. One of the methoxyl groups formed by methylation is unstable to acetylation by acetic anhydride in pyridine, heptamethyl alkali lignin yielding a hexamethyldiacetyl derivative, hexamethyl alkali lignin a pentamethyltriacetyl derivative, pentamethyl alkali lignin a tetramethyltetracetyl derivative, and anhydrotrimethyl alkali lignin the corresponding anhydrodimethyltetracetyl alkali lignin. Triphenylchloromethane in pyridine yields a monotrityl derivative.p-Nitrophenylhydrazine gives a di-p-nitrophenylhydrazone and phenylhydrazine a phenylhydrazone-osazone. Potentiometric titration shows two points of inflection and an equivalent weight of 863. The data are consistent with the empirical formula C92Hl04O34(1754) or C73H54O9,(OCH3)14,(OH)3,C(OH),CO-CH20H,C0,COOH

STUDIES ON STOBBE CONDENSATION: REACTIONS OF ALDEHYDES AND KETONES WITH DIMETHYL METHYLSUCCINATE

1965 ◽  
Vol 43 (4) ◽  
pp. 928-934 ◽  
Author(s):  
A. M. El-Abbady ◽  
H. H. Mousa
Keyword(s):  
Acetic Anhydride ◽  
Alkaline Hydrolysis ◽  
Sodium Acetate ◽  
Condensation Reactions ◽  
Aldehydes And Ketones ◽  
Hydrolysis Of

Benzaldehyde, o-methoxybenzaldehyde, p-chlorobenzaldehyde, benzophenone, and acetophenone are condensed with dimethyl methylsuccinate in the presence of potassium tert-butoxide to give the corresponding β-half-esters. In the case of o-methoxybenzaldehyde the lactonic acid (IX) is also obtained. The β-half-esters are cyclized by sodium acetate and acetic anhydride to the corresponding acetoxynaphthoates which are converted into their methoxynaphthoates. Alkaline hydrolysis of the β-half-esters yields the corresponding itaconic acids, the anhydrides of which are converted to their α-half-esters.

Synthesis of 9-(2-phosphonylmethoxyethyl)adenine and related compounds

1987 ◽  
Vol 52 (11) ◽  
pp. 2801-2809 ◽  
Author(s):  
Antonín Holý ◽  
Ivan Rosenberg
Keyword(s):  
Methyl Ester ◽  
Ethyl Ester ◽  
Sodium Salt ◽  
Alkaline Hydrolysis ◽  
Inorganic Phosphate ◽  
Sodium Hydride ◽  
Analogous Reaction ◽  
Hydrolysis Of ◽  
Related Compounds

Diethyl 2-hydroxyethoxymethanephosphonate (VIII) was converted into diethyl 2-halogenoethoxymethanephosphonates IXa and IXb by reaction with triphenylphosphine and tetrachloromethane or tetrabromomethane; analogous reaction of VIII with p-toluenesulfonyl chloride afforded diethyl 2-(p-toluenesulfonyloxy)ethoxymethanephosphonate (IXc). Reaction of sodium salt of adenine with compounds IX led to 9-(2-diethoxyphosphonylmethoxyethyl)adenine (X). Compound X was converted into 9-(2-phosphonylmethoxyethyl)adenine (II) by treatment with bromotrimethylsilane whereas alkaline hydrolysis of X gave ethyl ester Vb. Reaction of 9-(2-hydroxyethyl)adenine (IIIa) or its N6-benzoyl derivative IIIb with dimethyl p-toluenesulfonyloxymethanephosphonate (IV) in the presence of sodium hydride, followed by alkaline hydrolysis yielded methyl ester Va. Morpholide XI reacted with an inorganic phosphate and diphosphate to give 9-(2-phosphorylphosphonylmethoxyethyl)adenine (XII) and 2-(diphosphorylphosphonylmethoxyethyl)adenine (XIII), respectively.

Synthesis of conjugates of 1-(carboxymethyl)cytosine and 1-(5-O-carboxymethyl-β-D-arabinofuranosyl)cytosine with proteins

1979 ◽  
Vol 44 (10) ◽  
pp. 3023-3032 ◽  
Author(s):  
Helmut Pischel ◽  
Antonín Holý ◽  
Günther Wagner
Keyword(s):  
Human Serum Albumin ◽  
Acetic Anhydride ◽  
Serum Albumin ◽  
Human Serum ◽  
Activated Esters ◽  
Hydrolysis Of

1-(Carboxymethyl)cytosine (Ia), 1-(5-O-carboxymethyl-β-D-arabinofuranosyl)cytosine (IIa) and 5'-O-carboxylmethylcytidine (IIIa) were transformed by treatment with acetic anhydride and 4-dimethylaminopyridine to the peracetyl derivatives Ib-IIIb. These products reacted with p-nitrophenol in the presence of N, N'-dicyclohexylcarbodiimide to give the activated esters Ic-IIIc which on reaction with ammonia, dimethylamine or 2-aminoethanol afforded the corresponding carboxamides Id-IIId, IIe,f. Reactions of Ic and IIc with human serum albumin and bovine γ-globulin at pH 9.2, followed by hydrolysis of the N- or O-acetyl groups at pH 9.5, gave 50% up to 64% yields of the respective conjugates Ig, IIg and Ih, IIh.

Influence of medium on alkaline hydrolysis of succinic acid monomethyl and monopropyl esters

1980 ◽  
Vol 45 (11) ◽  
pp. 2873-2882
Author(s):  
Vladislav Holba ◽  
Ján Benko
Keyword(s):  
Succinic Acid ◽  
Kinetic Parameters ◽  
Alkaline Hydrolysis ◽  
Specific Interactions ◽  
Nonaqueous Media ◽  
The Media ◽  
Kinetics Of ◽  
Hydrolysis Of

The kinetics of alkaline hydrolysis of succinic acid monomethyl and monopropyl esters were studied in mixed aqueous-nonaqueous media at various temperatures and ionic strengths. The results of measurements are discussed in terms of electrostatic and specific interactions between the reactants and other components of the reaction mixture. The kinetic parameters in the media under study are related to the influence of the cosolvent on the solvation sphere of the reactants.

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