Synthesis of 5-Phenyl-2(1H)-pyrimidinone Nucleosides

1996 ◽  
Vol 61 (3) ◽  
pp. 458-477 ◽  
Author(s):  
Marcela Krečmerová ◽  
Hubert Hřebabecký ◽  
Milena Masojídková ◽  
Antonín Holý
Keyword(s):  
Thionyl Chloride ◽  
Chloroacetic Acid ◽  
Equilibrium Mixture ◽  
Side Product ◽  
Subsequent Reaction ◽  
Silyl Derivative ◽  
Tetrabutylammonium Fluoride ◽  
Trimethylsilyl Trifluoromethanesulfonate ◽  
Methanolic Ammonia ◽  
Tin Tetrachloride

Reaction of 2-phenyltrimethinium salt 1 with thiourea and subsequent reaction with chloroacetic acid afforded 5-phenyl-2(1H)-pyrimidinone (3). Its silyl derivative 4 was condensed with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose under catalysis with tin tetrachloride or trimethylsilyl trifluoromethanesulfonate to give protected nucleoside 5 together with 5',O6-cyclo-5-phenyl-1,3-bis- (β-D-ribofuranosyl)-6-hydroxy-5,6-dihydro-2(1H,3H)-pyrimidinone (7). The greatest amounts of 7 were formed with the latter catalyst. Nucleosidation of the silyl derivative 4 with protected methyl 2-deoxy-D-ribofuranoside 8 or 2-deoxy-D-ribofuranosyl chloride 9 afforded 1-(2-deoxy-3,5-di-O-p-toluoyl-β-D-ribofuranosyl)-5-phenyl-2(1H)-pyrimidinone (10) and its α-anomer 11. Reaction of 10 and 11 with methanolic ammonia gave free 2'-deoxynucleosides 12 and 13. Compound 13 was converted into 5'-O-tert-butyldiphenylsilyl-3'-O-mesyl derivative 14 which on heating with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and subsequent cleavage with tetrabutylammonium fluoride afforded 2',3'-dideoxy-2',3'-didehydronucleoside 15. Reaction of the silyl derivative 4 with 1,2-di-O-acetyl-3,5-di-O-benzoylxylofuranose (18), catalyzed with tin tetrachloride, furnished 1-(2-O-acetyl-3,5-di-O-benzoyl-β-D-xylofuranosyl)-2(1H)-pyrimidinone (19) which was deprotected to give the β-D-xylofuranosyl derivative 22. As a side product, the nucleosidation afforded the β-D-xylopyranosyl derivative 23. Deacetylation of compound 19 gave 1-(3,5-di-O-benzoyl-β-D-xylofuranosyl)-5-phenyl-2(1H)-pyrimidinone (24) which on reaction with thionyl chloride afforded 2'-chloro-2'-deoxynucleoside 25 and 2',O6-cyclonucleoside 26. Heating of compound 25 with DBU in dimethylformamide furnished the lyxo-epoxide 27 which on reaction with methanolic ammonia was converted into free 1-(2,3-anhydro-β-D-lyxofuranosyl)-5-phenyl-2(1H)-pyrimidinone (28). Reaction of 1,2-di-O-acetyl-5-O-benzoyl-3-O-methanesulfonyl-D-xylofuranose (30) with silyl derivative 4 gave the nucleoside 31 which by treatment with DBU was converted into an equilibrium mixture of 5'-benzoylated arabinofuranoside 33a and its 2',6-anhydro derivative 33b.

2',3'-Dideoxy- and 3'-Azido-2',3'-dideoxynucleosides of 5-Phenyl-2(1H)-pyrimidinone. Preparation of 2',3'-Dideoxypentofuranoses

1996 ◽  
Vol 61 (3) ◽  
pp. 478-488 ◽  
Author(s):  
Marcela Krečmerová ◽  
Hubert Hřebabecký ◽  
Milena Masojídková ◽  
Antonín Holý
Keyword(s):  
Acetic Anhydride ◽  
Thionyl Chloride ◽  
Benzoyl Chloride ◽  
Chromium Trioxide ◽  
Minor Amount ◽  
Subsequent Reduction ◽  
Silyl Derivative ◽  
Chloro Derivative ◽  
Trimethylsilyl Trifluoromethanesulfonate ◽  
Keto Derivative

The synthesis of methyl 3-azido-5-benzoyl-2,3-dideoxy-β-D-ribofuranoside (10) from methyl 2-deoxy-D-ribofuranoside (1) and its use for the preparation of 3'-azido-2',3'-dideoxy-β-D-ribofuranosides is described. Reaction of methylglucoside 1 with benzoyl chloride in pyridine afforded 5-O-benzoyl derivative 2, which on oxidation with complex of chromium trioxide, pyridine and acetic anhydride afforded 3-keto derivative 3. This was reduced with sodium borohydride in ethanol to give a mixture of methyl 2-deoxyglycosides of α-D-ribo- (4) and β-D-xylo- (5) configuration. Their mesyl derivatives 6 and 7 were chromatographically separated. Compound 7 reacted with sodium azide in hot dimethylformamide to afford methyl 3-azido-5-O-benzoyl-2,3-dideoxy-β-D-ribofuranoside (10). 5-Phenyl-2(1H)-pyrimidinone was converted into silyl derivative 11 by treatment with hexamethyldisilazane. Reaction of compound 11 with the azido sugar 10, catalyzed by trimethylsilyl trifluoromethanesulfonate, and subsequent methanolysis, furnished a mixture of anomeric 3'-azido-2',3'-dideoxynucleosides 14 and 15. Methyl 5-O-benzoyl-2,3-dideoxy-α-D-ribofuranoside (17) was prepared from methyl-α-glycoside 4 by reaction with thionyl chloride and subsequent reduction of the obtained 3-chloro derivative 16 with tributylstannane. Silyl derivative 11 reacted with 2,3-dideoxy sugar 17 under catalysis with trimethylsilyl triflate to give mainly 1-(5-O-benzoyl-2,3-dideoxy-α-D-glycero-pentofuranosyl)-5-phenyl-2(1H)-pyrimidinone (19) and minor amount of the β-anomer 18. Their methanolysis afforded dideoxynucleosides 20 and 21.

Facile Syntheses of Novel Acyclic Polycarboxylic Acids

2005 ◽  
Vol 60 (4) ◽  
pp. 408-412 ◽  
Author(s):  
Matthias Lutz ◽  
Jouni Pursiainen ◽  
Reijo Aksela
Keyword(s):  
Carboxylic Acids ◽  
Chloroacetic Acid ◽  
Reaction Step ◽  
Subsequent Reaction ◽  
Polycarboxylic Acids

The synthesis of novel di- and tricarboxylic acids is described. Starting from diethanolamine, a series of N-substituted diethanol derivatives were prepared which were converted in the subsequent reaction step into the corresponding carboxylic acids by treatment with chloroacetic acid. N,N-bis[2- (carboxymethoxy)ethyl]glycine was obtained by N-alkylation of glycine ethylester with ethyl 2-(2- bromoethoxy)acetate

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).

Anionic cis-trans isomerisation of dimethyl perfluoro-(4-methyl-2-pentene)dioate

1980 ◽  
Vol 45 (12) ◽  
pp. 3360-3369 ◽  
Author(s):  
Oldřich Paleta ◽  
Jiří Svoboda ◽  
Václav Havlů ◽  
Václav Dědek
Keyword(s):  
Proton Transfer ◽  
Title Compound ◽  
Heterogeneous System ◽  
Equilibrium Mixture ◽  
Potassium Fluoride ◽  
Side Product ◽  
Solvation Effect ◽  
Aprotic Solvents ◽  
Reaction Conditions ◽  
Dipolar Aprotic Solvents

Potassium fluoride induced cis-trans isomerisation of the title compound I was investigated. The isomerisation takes place in a heterogeneous system and is enabled by solvation effect of dipolar aprotic solvents. Dimethyl 2,3,3,4-tetrafluoro-2-trifluoromethylpentanedioate (II) is formed as side product by proton transfer from the solvent to the intermediate 1,3-bis(methoxycarbonyl)perfluoro-1-butanide (III). The mechanism was deduced from the reaction conditions and results of the isomerisation. Composition of the equilibrium mixture of cis- and trans-isomer (Ia, Ib, respectively) studied in the interval 2-75 °C, shows an extreme. In the interval 2-30 °C the reaction Ia → Ib appears to be exothermic (ΔH = -21.2 kJ mol-1), in the interval 35-47 °C the enthalpy equals practically zero and in the maximum of the curve at 42.5 °C the entropic factor ΔS = 2.82 J mol-1 K-1. In the interval 50-75 °C the reaction is endothermic (ΔH = 15.2 kJ mol-1). In this context the effect of steric interactions between the substituents -COOCH3 and -CF(CF3)COOCH3, as well as of the so called cis-effect in 1,2-dihalogenoethylenes, on the Ia ##e Ib equilibrium are discussed.

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 of Deoxy, Dideoxy and Didehydrodideoxy Analogs of 9-(β-D-Hexofuranosyl)adenine

1994 ◽  
Vol 59 (6) ◽  
pp. 1408-1419 ◽  
Author(s):  
Hubert Hřebabecký ◽  
Jan Dočkal ◽  
Antonín Holý
Keyword(s):  
Antiviral Activity ◽  
Catalytic Hydrogenation ◽  
Sodium Methoxide ◽  
Reductive Elimination ◽  
Bromo Derivative ◽  
Epoxy Derivative ◽  
Subsequent Deacetylation ◽  
Methanolic Ammonia ◽  
Tin Tetrachloride

Condensation of 1,2-di-O-acetyl-3,5,6-tri-O-benzoyl-D-glucofuranose with N6-benzoyladenine, catalyzed with tin tetrachloride, afforded nucleoside I. Partial deacetylation of I, followed by mesylation, gave 9-(3,5,6-tri-O-benzoyl-2-O-methanesulfonyl-β-D-glucofuranosyl)adenine (III). 9-(2,5,6-Tri-O-acetyl-3-O-methanesulfonyl-β-D-glucofuranosyl)-N6-benzoyladenine (IV) was prepared by condensation of 1,2,5,6-tetra-O-acetyl-3-O-methanesulfonyl-D-glucofuranose with N6-benzoyladenine. Reaction of mesyl derivative III with methanolic sodium methoxide and of mesyl derivative IV with methanolic ammonia led to 2',3'-anhydronucleosides V and VI which were acetylated to give the respective 9-(5,6-di-O-acetyl-2,3-anhydro-β-D-mannofuranosyl)adenine (VII) and 9-(5,6-di-O-acetyl-2,3-anhydro-β-D-allofuranosyl)adenine (VIII). Epoxy derivative VII was cleaved with bromotrimethylsilane, affording a mixture of 9-(5,6-di-O-acetyl-2-bromo-2-deoxy-β-D-glucofuranosyl)adenine (Xa) and 9-(5,6-di-O-acetyl-3-bromo-3-deoxy-β-D-altrofuranosyl)adenine (XIa), epoxy derivative VIII was cleaved analogously to give 9-(5,6-di-O-acetyl-3-bromo-3-deoxy-β-D-glucofuranosyl)adenine (XIIa). Their dehalogenation with tributylstannane and subsequent deacetylation led to 9-(2-deoxy-β-D-arabino-hexofuranosyl)adenine (Xc), 9-(3-deoxy-β-D-arabino-hexofuranosyl)adenine (XIc) and 9-(3-deoxy-β-D-ribo-hexofuranosyl)adenine (XIIc). 9-(2,5,6-Tri-O-acetyl-3-bromo-3-deoxy-β-D-glucofuranosyl)adenine (XIId), which was prepared by acetylation of XIIa, on reductive elimination with Cu/Zn couple and subsequent deacetylation gave 9-(2,3-dideoxy-β-D-erythro-hex-2-enofuranosyl)adenine (XIV). 9-(2,3-Dideoxy-β-D-erythro-hexofuranosyl)adenine (XVI) was obtained either by catalytic hydrogenation of bromo derivative XIId followed by deacetylation, or by catalytic hydrogenation of didehydro derivative XIV. The synthesized nucleosides were tested for antiviral activity.

scholarly journals Synthesis of Some new 2-(4-Aryliminophenoxy)N-Arylacetamide Via p-hydroxy benzaldehyde.

2014 ◽  
Vol 11 (2) ◽  
pp. 486-490
Author(s):  
Baghdad Science Journal
Keyword(s):  
Schiff Bases ◽  
Thionyl Chloride ◽  
Aromatic Amines ◽  
Chloroacetic Acid ◽  
Spectroscopic Methods ◽  
Chloroacetyl Chloride ◽  
Primary Aromatic Amine ◽  
Primary Aromatic Amines ◽  
New Compounds ◽  
Williamson Reaction

Chloroacetamide derivatives (2a-g) have been prepared through reaction of chloroacetyl chloride(1) (which prepared by the reaction of chloroacetic acid with thionyl chloride) with primary aromatic amines and sulfa compounds to afford compounds (2a-g) which then reacted with p-hydroxy benzaldehyde via Williamson reaction to obtaine the new compounds 2-(4-formyl phenoxy)-N-aryl acetamide (3a-g). Finally , compounds (3a-g) will be use as a good synthon to prepare the Schiff bases represented by compounds 2-(4-aryliminophenoxy)-N-arylacetamide (4a-g). through , reaction with some primary aromatic amine. All the prepared compounds were investigated by the available physical and spectroscopic methods.

Nucleic acid related compounds. 66. Improved syntheses of 5′-chloro-5′-deoxy- and 5′-S-aryl(or alkyl)-5′-thionucleosides

1991 ◽  
Vol 69 (9) ◽  
pp. 1468-1474 ◽  
Author(s):  
Morris J. Robins ◽  
Fritz Hansske ◽  
Stanislaw F. Wnuk ◽  
Tadashi Kanai
Keyword(s):  
Ambient Temperature ◽  
Thionyl Chloride ◽  
Hydroxyl Group ◽  
Key Words Adenosine ◽  
Nucleophilic Displacement ◽  
Cyclic Sulfite ◽  
High Yields ◽  
Work Up ◽  
Related Compounds ◽  
Methanolic Ammonia

Treatment of ribonucleosides with thionyl chloride/pyridine/acetonitrile (0 °C to ambient temperature) resulted in essentially quantitative formation of 5′-chloro-5′-deoxy-2′,3′-O-sulfinylnucleoside derivatives. These diastereomeric sulfite esters underwent deprotection readily with aqueous methanolic ammonia. This gave 5′-chloro-5′-deoxynucleosides without use of the suspected carcinogen, hexamethylphosphoramide (HMPA). Nucleophilic displacement with sodium thiolates in dimethylformamide (−30 °C to ambient temperature) gave 5′-S-aryl(or alkyl)-5′-thionucleosides in high yields. Treatment of ribonucleosides with thionyl chloride/acetonitrile without pyridine followed by aqueous work-up gave diastereomeric 2′,3′-O-sulfinylnucleosides with an unmodified 5′-hydroxyl group. Diagnostic NMR shifts for cyclic sulfite ester stereochemistry are noted. Key words: adenosine, 5′-S-aryl(or alkyl)-5′-thionucleosides, 5′-chloro-5′-deoxynucleosides, uridine, nucleosides.

Synthesis of Novel Chiral Pyrimidone Salts and their Application in Asymmetric Diethylzinc Addition of Arylaldehydes

2018 ◽  
Vol 15 (1) ◽  
pp. 137-142 ◽  
Author(s):  
Bi-Hui Zhou ◽  
Wei-Ping He ◽  
Lin-Lin Li ◽  
Li-Mei Fan ◽  
Xiang-Rong Li ◽  
...  
Keyword(s):  
Thionyl Chloride ◽  
Lithium Aluminum Hydride ◽  
Secondary Alcohol ◽  
Aluminum Hydride ◽  
Heterocyclic Carbenes ◽  
Ammonium Salts ◽  
Lithium Aluminum ◽  
Partial Reduction ◽  
Subsequent Reaction ◽  
Efficient Route

Aims and Objectives: When compared to five-membered N-heterocyclic carbene, recent reports have demonstrated that ring expanded NHCs showed rather different properties such as increased basicity (nucleophilicity) and greater steric demand. These unique features provide an opportunity to design new chiral ligands. This study was undertaken to design and synthesize a series of novel enantiopure pyrimidone salts, the precursors of N-heterocyclic carbenes, and their activity in asymmetric diethylzinc addition of arylaldehydes was demonstrated as well. Materials and Method: Commercially available dimethylmalonic acid was treated with thionyl chloride to form dimethylmalony dichloride, followed by subsequent reaction with different chiral primary amine produced corresponding diamide. Next, conversion of diamide to monoamide was achieved by partial reduction with lithium aluminum hydride. Finally, cyclization of monoamide with triethyl orthoformate in the presence of ammonium salts provided pyrimidone salts in good yields. Results: Seven enantiopure pyrimidone salts, the precursors of N-heterocyclic carbenes, have been synthesized starting from dimethylmalonic acid. Their applicability in asymmetric diethylzinc addition of arylaldehydes has been demonstrated and the corresponding secondary alcohol was obtained with good yields and moderate enantioselectivities. Conclusion: Herein we developed an efficient route to prepare a series of novel N-heterocyclic carbene precursors, which were demonstrated as effective catalysts for asymmetric diethylzinc addition of arylaldehydes, and the corresponding secondary alcohol was obtained with good yields and moderate enantioselectivities.

Sign in / Sign up

Export Citation Format

Share Document