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.

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.

Chemistry of Fenchonesulfonic Acid Derivatives

1995 ◽  
Vol 50 (2) ◽  
pp. 283-288 ◽  
Author(s):  
Gabriele Wagner ◽  
Uwe Verfürth ◽  
Rudolf Herrmann
Keyword(s):  
Acetic Anhydride ◽  
Thionyl Chloride ◽  
Sulfonic Acid ◽  
Reaction Rate ◽  
Enantiomeric Excess ◽  
Methyl Group ◽  
Close Analogy ◽  
Chiral Sulfoxides ◽  
Mndo Calculations ◽  
Nmr Techniques

(1 S) - (+)-Fenchone is sulfonated by SO3 or H2SO4/acetic anhydride in the bridgehead methyl group. This could be confirmed by NMR techniques (INADEQUATE). The fenchonesulfonic acid obtained is converted (SOCl2/NH3) to the cyclic fenchonesulfonimide, which can be oxidized to the corresponding oxaziridine, in close analogy to 10-camphorsulfonimide. Improved procedures for this reaction sequences are given. During the treatment of the sulfonic acid with thionyl chloride, a byproduct with a rearranged bicyclic skeleton is observed whose structure has been determined by ozonolytic degradation and NMR techniques. A possible mechanism for this rearrangement is suggested, based on MNDO calculations of the intermediate carbocations. The fenchonesulfonyloxaziridine oxidizes sulfides to chiral sulfoxides with appreciable enantiomeric excess, but very low reaction rate. A comparison with camphor-derived oxaziridines having similar steric requirements is made.

2',3'-O-Carbonyl derivatives of 6-azauridine in the synthesis of its 5-substituted and 5'-deoxy derivatives

1987 ◽  
Vol 52 (8) ◽  
pp. 2070-2082
Author(s):  
Pavel Drašar ◽  
Jiří Beránek
Keyword(s):  
Thionyl Chloride ◽  
Alkaline Hydrolysis ◽  
Triphenyl Phosphine ◽  
Carbonyl Derivatives ◽  
Tributyltin Hydride ◽  
Chloro Derivative ◽  
Ammonium Halides ◽  
Chloro Derivatives ◽  
Derivatives Of ◽  
Dichloro Derivative

Preparation of 2',3'-O-carbonyl derivatives of 5'-deoxy-6-azauridine and 6-azauridine using 1,1'-carbonyldiimidazole has been elaborated. 5'-Chloro and 5'-bromo derivatives were prepared by treatment of the 5'-O-mesyl derivative with quaternary ammonium halides, 5'-chloro derivatives also by direct halogenation with thionyl chloride in hexamethylphosphortriamide or with tetrachloromethane, triphenyl phosphine, and dimethylformamide. Derivatives of 5'-bromo-6-azauridine were reduced with tributyltin hydride to 5'-deoxy-6-azauridine compounds. 6-Azauridine 2',3'-carbonate (IVa) and its 5'-derivatives IVc and IVe on treatment with imidazole in dimethylformamide afforded 2,2'-anhydronucleosides IIIa-IIIc. The 2,2'-anhydro-5'-deoxy compound IIIc underwent alkaline hydrolysis to 5'-deoxy-1-β-D-arabino-pentofuranosyl-6-azauracil (VIa). Treatment of 2,2'-anhydro-5'-deoxy-5'-chloro derivative IIIb with hydrogen chloride led to 2',5'-dichloro derivative If.

scholarly journals Efficient Synthesis of α-Branched Purine-Based Acyclic Nucleosides: Scopes and Limitations of the Method

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4307
Author(s):  
Jan Frydrych ◽  
Lenka Poštová Slavětínská ◽  
Martin Dračínský ◽  
Zlatko Janeba
Keyword(s):  
Acetic Anhydride ◽  
Room Temperature ◽  
Side Chain ◽  
Efficient Synthesis ◽  
Purine Derivatives ◽  
Aliphatic Side Chain ◽  
Acyclic Nucleosides ◽  
Efficient Route ◽  
High Yields ◽  
Trimethylsilyl Trifluoromethanesulfonate

An efficient route to acylated acyclic nucleosides containing a branched hemiaminal ether moiety is reported via three-component alkylation of N-heterocycle (purine nucleobase) with acetal (cyclic or acyclic, variously branched) and anhydride (preferentially acetic anhydride). The procedure employs cheap and easily available acetals, acetic anhydride, and trimethylsilyl trifluoromethanesulfonate (TMSOTf). The multi-component reaction is carried out in acetonitrile at room temperature for 15 min and provides moderate to high yields (up to 88%) of diverse acyclonucleosides branched at the aliphatic side chain. The procedure exhibits a broad substrate scope of N-heterocycles and acetals, and, in the case of purine derivatives, also excellent regioselectivity, giving almost exclusively N-9 isomers.

α-(4-Tolyl)dopamine, derivatives and analogues; Synthesis and pharmacological screening

1983 ◽  
Vol 48 (5) ◽  
pp. 1447-1464 ◽  
Author(s):  
Vladimír Valenta ◽  
Jiří Holubek ◽  
Emil Svátek ◽  
Antonín Dlabač ◽  
Marie Bartošová ◽  
...  
Keyword(s):  
Acetic Anhydride ◽  
Hydrobromic Acid ◽  
Benzoyl Chloride ◽  
Substitution Reactions ◽  
Low Degree ◽  
Anticataleptic Activity ◽  
Pharmacological Screening ◽  
Higher Doses ◽  
Hydroxyethyl Piperazine ◽  
Antiarrhythmic Effects

The ketone XIII, obtained by Friedel-Crafts reaction of toluene with homoveratroyl chloride, was converted by the Leuckart reaction to the formamido derivative IXb which was used as the starting product for the synthesis of amines IIIb-Vb. Reduction of the ketone XIII gave the alcohol XVI which was treated with hydrogen chloride and afforded the chloro compound XVII. Its substitution reactions with 1-methylpiperazine, 1-(2-hydroxyethyl)piperazine and 1-phenylpiperazine resulted in the piperazines VIb-VIIIb. Acylations of the amine IIIb with acetic anhydride and homoveratroyl chloride gave the amides Xb and XIb which, together with the formamide IXb, were subjected to the Bischler-Napieralski reaction. 3,4-Dihydroisoquinolines XXII-XXIV were obtained and reduced to the 1,2,3,4-tetrahydroisoquinolines XXVb-XXVIIb. Treatment of XXVIIb with formaldehyde afforded the berbine derivative XXVIII. Demethylation of the amine IIIb with hydrobromic acid resulted in the title compound IIIa. Similar demethylations of the dimethoxyamines IVb-VIIIb, XXVb and XXVIb led to the dihydroxyamines IVa-VIIIa, XXVa and XXVIa which are dopamine derivatives. Reaction of Va with benzoyl chloride gave the dibenzoate XXX. The CNS activities of the compounds prepared are of a low degree. Several of them (IIIa-VIa, IIIb-Vb, XXVb) show in higher doses signs of central stimulant action but only for compound IVa an antireserpine effect was proven. The expected anticataleptic activity was found only in a low degree with compound VIIIa; on the contrary, compounds IIIa and XXVa are procataleptogenic. Some compounds (IIIa, IXb, XXVIa, XXVIII) potentiated thiopental. In single cases local anaesthetic, spasmolytic, hypotensive, hypertensive, hypoglycaemic, diuretic and antiarrhythmic effects were observed.

scholarly journals Enaminonitrile as Building Block in Heterocyclic Synthesis: Synthesis of Novel 4H-Furo[2,3-d][1,3]oxazin-4-one and Furo[2,3-d]pyrimidin-4(3H)-one Derivatives

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Manal M. El-Shahawi ◽  
Ahmed K. El-Ziaty
Keyword(s):  
Acetic Anhydride ◽  
Building Block ◽  
Benzoyl Chloride ◽  
Heterocyclic Synthesis ◽  
Elemental Analyses ◽  
Nitrogen Nucleophiles

2-Amino-4,5-diphenylfuran-3-carbonitrile 1 was utilized as building block for the construction of new furo[2,3-d]pyrimidin-4(3H)-one derivative 2 and 4H-furo[2,3-d][1,3]oxazin-4-one derivative 3 via treatment with acetic anhydride and benzoyl chloride, respectively. The 4H-furo[2,3-d][1,3]oxazin-4-one derivative 3 was transformed into novel furo[2,3-d]pyrimidin-4(3H)-ones 4–8, tetrazolylfuran derivative 10, and furo[3,2-d]imadazolone derivative 11 via reaction with various nitrogen nucleophiles. The structure features of the synthesized compounds were established from their spectral and elemental analyses.

Aminodideoxy sugars. Methyl 3-acetamido-2,3-dideoxy-α-D-arabino-hexopyranoside and methyl 2-acetamido-2,3-dideoxy-α-D-ribo-hexopyranoside

1969 ◽  
Vol 47 (15) ◽  
pp. 2747-2750 ◽  
Author(s):  
Alex Rosenthal ◽  
P. Catsoulacos
Keyword(s):  
Acetic Acid ◽  
Acetic Anhydride ◽  
Minor Amount ◽  
Yield Reduction ◽  
Aqueous Acetic Acid ◽  
Lithium Aluminium Hydride ◽  
Parallel Reaction ◽  
Lithium Aluminium ◽  
Methyl Sulfoxide ◽  
A Minor

Oxidation of methyl 4,6-O-benzylidene-3-deoxy-α-D-arabino-hexopyranoside (2) with methyl sulfoxide and acetic anhydride yielded methyl 4,6-O-benzylidene-3-deoxy-α-D-erythro-hexopyranosid-2-ulose (3) in an 80% yield. Reduction of the oximino derivative of 3 with lithium aluminium hydride in tetrahydrofuran or with diborane afforded, after acetylation, methyl 2-acetamido-4,6-O-benzylidene-2,3-dideoxy-α-D-ribo-hexopyranoside (6) in a 44% yield. The latter was also debenzylidenated with aqueous acetic acid. In a parallel reaction, methyl 4,6-O-benzylidene-2,3-dideoxy-3-oximino-α-D-erythro-hexopyranoside yielded mainly methyl 3-acetamido-4,6-O-benzylidene-2,3-dideoxy-α-D-arabino- (and a minor amount of the ribo-epimer)-hexopyranoside.

THE ALCOHOLYSIS OF TRIALKYLALKOXYSILANES: PART II. THE PREPARATION AND CHEMISTRY OF METHYL 2,3,4-TRI-O-TRI-METHYLSILYL-α-D-GLUCOPYRANOSIDE

1965 ◽  
Vol 43 (7) ◽  
pp. 2004-2011 ◽  
Author(s):  
D. T Hurst ◽  
A. G. McInnes
Keyword(s):  
Magnetic Resonance ◽  
Acetic Anhydride ◽  
Proton Magnetic Resonance ◽  
Benzoyl Chloride ◽  
Phenyl Isocyanate ◽  
High Yield ◽  
Aqueous Methanol ◽  
Trimethylsilyl Group ◽  
Acidic Catalysts ◽  
Derivatives Of

The trimethylsilyl group on the 6-position of methyl 2,3,4,6-tetra-O-trimethylsilyl-α-D-glucopyranoside is preferentially removed by methanolysis, using basic or acidic catalysts, giving methyl 2,3,4-tri-O-trimethylsilyl-α-D-glucopyranoside in high yield (>80%). Reaction of the latter with acetic anhydride, benzoyl chloride, or phenyl isocyanate produces the corresponding 6-substituted derivatives in quantitative yield. The trimethylsilyl residues from the latter compounds are hydrolyzed by 50% aqueous methanol with the concomitant formation of 6-O-acetyl, 6-O-benzoyl, or 6-carbanilate derivatives of methyl α-D-glucopyranoside in excellent yield. Chemical and proton magnetic resonance (p.m.r.) studies established the structure of methyl 2,3,4-tri-O-trimethylsilyl-α-D-glucopyranoside, and of subsequent derivatives prepared from this compound. Infrared and p.m.r. evidence is offered to support conclusions regarding the conformation of the groups or atoms attached to C6 and C5 of the glucoside residue in some of these compounds.

Sign in / Sign up

Export Citation Format

Share Document