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.

Synthesis of Deoxy, Dideoxy and Didehydrodideoxy Analogs of 9-(4-C-Hydroxymethyl-α-L-pentofuranosyl)adenine

1994 ◽  
Vol 59 (7) ◽  
pp. 1654-1664 ◽  
Author(s):  
Hubert Hřebabecký ◽  
Antonín Holý
Keyword(s):  
Antiviral Activity ◽  
Catalytic Hydrogenation ◽  
Sodium Methoxide ◽  
Reductive Elimination ◽  
Bromo Derivative ◽  
Epoxy Derivative ◽  
Subsequent Deacetylation ◽  
Tin Tetrachloride

Condensation of 1,2-di-O-acetyl-3,5-di-O-benzoyl-4-C-benzoyloxymethyl-L-arabinofuranose with N6-benzoyladenine, catalyzed with tin tetrachloride, afforded nucleoside I, which upon partial deacetylation and subsequent mesylation was converted into 9-(3,5-di-O-benzoyl-4-C-benzoyloxymethyl-2-O-methanesulfonyl-α-L-arabinofuranosyl)adenine (III). 9-(2,5,6-Tri-O-acetyl-4-C-acetoxymethyl-3-O-methanesulfonyl-α-L-arabinofuranosyl)-N6-benzoyladenine (V) was obtained by condensation of 1,2,5-tri-O-acetyl-4-C-acetoxymethyl-3-O-methanesulfonyl-L-arabinose with N6-benzoyladenine. Reaction of mesyl derivatives III and V with methanolic sodium methoxide afforded 2',3'-anhydro nucleosides VIa and VIIa, which were acetylated to give 9-(5-O-acetyl-4-C-acetoxymethyl-2,3-anhydro-α-L-ribofuranosyl)adenine (VIb) and 9-(5-O-acetyl-4-C-acetoxymethyl-2,3-anhydro-α-L-lyxofuranosyl)adenine (VIIb). Epoxy derivative VIb was cleaved with bromotrimethylsilane to 9-(5-O-acetyl-4-C-acetoxymethyl-2-bromo-2-deoxy-α-L-arabinofuranosyl)adenine (VIIIa); the same reaction with epoxy derivative VIIb afforded a mixture of 9-(5-O-acetyl-4-C-acetoxymethyl- 2-bromo-2-deoxy-α-L-xylofuranosyl)adenine (IXa) and 9-(5-O-acetyl-4-C-acetoxymethyl-3-bromo- 3-deoxy-α-L-arabinofuranosyl)adenine (Xa). Their dehalogenation with tributylstannane and subsequent deacetylation led to 9-(2-deoxy-4-C-hydroxymethyl-α-L-erythro-pentofuranosyl)adenine (VIIIc), 9-(2-deoxy-4-C-hydroxymethyl- α-L-threo-pentofuranosyl)adenine (IXc) and 9-(3-deoxy-4-C-hydroxymethyl-α-L-threo-pentofuranosyl)adenine (Xc). 9-(2,5-Di-O-acetyl-4-C-acetoxymethyl-2-bromo-2-deoxy-α-L-arabinofuranosyl)adenine (VIIId), prepared by acetylation of VIIIa, on reductive elimination with Cu/Zn couple and subsequent deacetylation afforded 9-(2,3-dideoxy-4-C-hydroxymethyl-α-L-glycero-pent-2-enofuranosyl)adenine (XIb). 9-(2,3-Dideoxy-4-C-hydroxymethyl-α-L-glycero-pentofuranosyl)adenine (XIIb) was obtained either by catalytic hydrogenation of bromo derivative VIIId, followed by deacetylation, or by catalytic hydrogenation of didehydro derivative XIb. The nucleosides synthesized were tested for antiviral activity.

Synthetic use of the ribosyl derivatives of 2,4- and 2,5-thiazolidinediones

1979 ◽  
Vol 44 (5) ◽  
pp. 1475-1482 ◽  
Author(s):  
Hubert Hřebabecký ◽  
Zdeněk Točík ◽  
Jiří Beránek
Keyword(s):  
Hydrazine Hydrate ◽  
Hydrogen Chloride ◽  
Sodium Methoxide ◽  
Aqueous Ammonia ◽  
Hydroxylamine Hydrochloride ◽  
Acetyl Derivative ◽  
High Yield ◽  
Derivatives Of ◽  
Methanolic Ammonia

On ribosidation of 2,4-thiazolidinedione (2,5-thiazolidinedione, respectively), the 3-β-D-ribofuranosyl derivative is formed in high yield, either the benzoyl derivative Ia (IIa) or the acetyl derivative Ib (IIb). The unsubstituted ribosyl derivative Ic is formed from the acetyl derivative Ib by methanolic hydrogen chloride. The benzoylated ribosyl-2,4-thiazolidinedione Ia affords the benzoylated ribosylurea III on reaction with aqueous ammonia, the hydroxyethylurea derivative IVa with 2-aminoethanol, the semicarbazide derivative Va with hydrazine hydrate, the ribosylhydroxyurea derivative VIa on reaction with hydroxylamine hydrochloride and triethylamine, the benzoyl derivative of ribosylbiuret VII with O-methylisourea hydrochloride and triethylamine, and (analogously) ribosylisothiobiuret VIII with S-methylisothiourea. Methanolysis of the benzoyl derivative of hydroxyethylurea IVa with sodium methoxide affords the unprotected riboside IVb. Ribosylhydroxyurea VIb is formed on debenzoylation of compound VIa with methanolic ammonia. Acetylation of compound VIb furnishes the pentaacetyl derivative VIc.

Über 5-Hydroxymethyl-cytidin und 5-Hydroxymethyl-cytosin-N-3-β-D-glucopyranosid sowie über reaktionsfähige Vorstufen

1966 ◽  
Vol 21 (10) ◽  
pp. 942-952 ◽  
Author(s):  
Reinhard Brossmer ◽  
Erich Röhm
Keyword(s):  
Hydrochloric Acid ◽  
Benzyl Alcohol ◽  
Catalytic Hydrogenation ◽  
Sodium Methoxide ◽  
Room Temperature ◽  
Selective Removal ◽  
Protecting Groups ◽  
Hydroxymethyl Cytosine ◽  
Analogous Manner ◽  
Synthetic Intermediates

5-Benzyloxymethyl-NNH2-benzoyl-cytosine (4) is formed from 5-hydroxymethyl-cytosine (1) in 80% yield by benzylation and subsequent benzoylation. The benzylation readily takes place with benzyl alcohol and catalytic amounts of hydrochloric acid in tetrahydrothiophen-1.1-dioxide as solvent. — 4 is quantitatively converted in pyridine at room temperature to a toluene soluble mercury (II) salt 5.5 condenses easily with 2.3.5-tribenzoyl-D-ribofuranosyl chloride to give the β-nucleoside 6, no a-anomer being found. — The removal of all protecting groups by catalytic hydrogenation and treatment with sodium methoxide or ammonia leads to cristalline 5-hydroxymethyl cytidine 10 (ca. 60% yields based on 1). — In an analogous manner N-3-β-D-glucosyl-5-hydroxymethyl-cytosine 15 is prepared. — Selective removal of certain of the protecting groups in 6 and 11 yields potentially valuable synthetic intermediates.

Synthesis of 2-amino-2-deoxy-D-talose and 2-amino-2-deoxy-D-galactose

1968 ◽  
Vol 46 (15) ◽  
pp. 2481-2484 ◽  
Author(s):  
M. B. Perry ◽  
Ann C. Webb
Keyword(s):  
Hydrochloric Acid ◽  
Sodium Methoxide ◽  
Ammonia Solution ◽  
Nef Reaction ◽  
Derivatives Of ◽  
Methanolic Ammonia

Treatment of D-lyxose with nitromethane in the presence of sodium methoxide gave 1-deoxy-1-nitro-D-galactitol which, after conversion to 2,3,4,5,6-penta-O-acetyl-1-deoxy-1-nitro-D-galactitol, reacted with saturated methanolic ammonia solution to yield 2-acetamido-1,2-dideoxy-1-nitro-D-talitol and 2-acetamido-1,2-dideoxy-1-nitro-D-galactitol. 2-Acetamido-1,2-dideoxy-1-nitro-D-talitol and 2-acetamido-1,2-dideoxy-1-nitro-D-galactitol were converted by a modified Nef reaction to 2-acetamido-2-deoxy-D-talose and 2-acetamido-2-deoxy-D-galactose which on hydrolysis with hydrochloric acid afforded 2-amino-2-deoxy-D-talose hydrochloride and 2-amino-2-deoxy-D-galactose hydrochloride. The properties and derivatives of the aminoglycoses are described.

Cyclizations of dialdehydes with nitromethane. XIV. The isolation of four crystalline methyl 3,6-dideoxy-3-nitro-α-L-hexopyranosides

1969 ◽  
Vol 47 (1) ◽  
pp. 99-103 ◽  
Author(s):  
Hans H. Baer ◽  
Karel Čapek
Keyword(s):  
Reaction Time ◽  
Catalytic Hydrogenation ◽  
Chromatographic Separation ◽  
Sodium Methoxide ◽  
Room Temperature ◽  
Total Yield

Cyclization of L′-methoxy-L-methyldiglycolic aldehyde (1) with nitromethane and sodium methoxide in methanol (40 min at room temperature) furnished four crystalline methyl 3,6-dideoxy-3-nitro-α-L-hexopyranosides in a combined yield of 75%. Chromatographic separation gave the gluco (2), manno (3), talo (4), and galacto (5) isomers in an approximate ratio of 18:8:3:1. Shortening of the reaction time to 25 min decreased the total yield to 53% at the expense of 2, the ratio of isolated products being 8:8:2.3:1.7. The configurations of the new nitro glycosides 3, 4, and 5 were proven by catalytic hydrogenation followed by N-acetylation, which gave the known 3-acetamido derivatives.

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.

Mechanistic insights into hydride transfer for catalytic hydrogenation of CO2 with cobalt complexes

2014 ◽  
Vol 43 (31) ◽  
pp. 11803-11806 ◽  
Author(s):  
N. Kumar ◽  
D. M. Camaioni ◽  
M. Dupuis ◽  
S. Raugei ◽  
A. M. Appel
Keyword(s):  
Catalytic Hydrogenation ◽  
Hydride Transfer ◽  
Cobalt Complexes ◽  
Reductive Elimination ◽  
Hydrogenation Of Co2 ◽  
Hydrogenation Of Co

The catalytic hydrogenation of CO2 to formate by Co(dmpe)2H can proceed via direct hydride transfer or via CO2 coordination to Co followed by reductive elimination of formate.

Synthesis of 1-(3-Azido-2,3-dideoxy-β-D-ribo-hexofuranosyl)-, 1-(2,3-Dideoxy-β-D-erythro-hexofuranosyl)- and 1-(2,3-Dideoxy-β-D-erythro-hex-2-enofuranosyl)pyrimidine Nucleosides

1994 ◽  
Vol 59 (2) ◽  
pp. 412-420 ◽  
Author(s):  
Hubert Hřebabecký ◽  
Antonín Holý
Keyword(s):  
Catalytic Hydrogenation ◽  
Pyrimidine Nucleosides ◽  
Lawesson’S Reagent ◽  
Lawesson's Reagent ◽  
Methanolic Ammonia

1-(3-Azido-2,3-dideoxy-β-D-ribo-hexofuranosyl)uracil (XXII) and 1-(2,3-dideoxy-β-D-erythro-hex-2-enofuranosyl)uracil (VIII) were prepared starting from 1-(2-O-acetyl-3,5,6-tri-O-benzoyl-β-D-glucofuranosyl)uracil (I) by a procedure described previously for thymine analogs. 1-(2,3-Dideoxy-β-D-erythro-hexofuranosyl)uracil (XIII) was obtained by catalytic hydrogenation of 1-(5,6-di-O-benzoyl-2,3-dideoxy-β-D-erythro-hex-2-enofuranosyl)uracil (VII) and subsequent methanolysis. Reaction of dibenzoyl derivative VII, 1-(5,6-di-O-benzoyl-2,3-dideoxy-β-D-erythro-hexofuranosyl)uracil (XII) and the diacetate prepared by acetylation of azido derivative XXII with Lawesson's reagent, followed by methanolysis, afforded 1-(2,3-dideoxy-β-D-erythro-hex-2-enofuranosyl)-4-thiouracil (X), 1-(2,3-dideoxy-β-D-erythro-hexofuranosyl)-4-thiouracil (XV) and 1-(3-azido-2,3-dideoxy-β-D-ribo-hexofuranosyl)-4-thiouracil (XXIII), respectively. Heating of thio derivatives X, XV and XXIII with methanolic ammonia at 100 °C gave 1-(2,3-dideoxy-β-D-erythro-hex-2-enofuranosyl)cytosine (XI), 1-(2,3-dideoxy-β-D-erythro-hexofuranosyl)cytosine (XVI) and 1-(3-azido-2,3-dideoxy-β-D-ribo-hexofuranosyl)cytosine (XXIV).

Branched-chain aminodeoxy sugars. Methyl 3-C-aminomethyl-2-deoxy-α-D-ribo-hexopyranoside and methyl 3-C-aminomethyl-2-deoxy-α-D-arabino hexopyranoside

1970 ◽  
Vol 48 (19) ◽  
pp. 3034-3038 ◽  
Author(s):  
Alex Rosenthal ◽  
Khong-Seng Ong
Keyword(s):  
Catalytic Hydrogenation ◽  
Sodium Methoxide ◽  
Acetyl Derivative ◽  
Molar Equivalent ◽  
Branched Chain

Addition of methyl 4,6-O-benzylidene-2-deoxy-α-D-erythro-hexopyranosid-3-ulose (1) to excess nitromethane and 1 molar equivalent of sodium methoxide in methanol gave methyl 4,6-O-benzylidene-2-deoxy-3-C-nitromethyl-α-D-ribo-hexopyranoside (2) and the arabino stereoisomer 3 in 63 and 22% yields, respectively. The proof of structure of the branched-chain deoxy nitro sugars is described. Debenzylidenation of the nitro sugars afforded the partially blocked nitro sugars 4 and 5. Catalytic hydrogenation of the latter or of 2 and 3 yielded the branched-chain aminodeoxy sugars 7 and 9 (7 characterized as its N-acetyl derivative and 9 as its N-2,4-dinitrophenyl derivative).

Immunocytochemical localization of desmin and vimentin in chick embryonic myocardial cells

1990 ◽  
Vol 48 (3) ◽  
pp. 448-449
Author(s):  
Yukiko Sugi
Keyword(s):  
Sodium Methoxide ◽  
Intermediate Filament Protein ◽  
Chick Embryos ◽  
Immunocytochemical Localization ◽  
Myocardial Cells ◽  
Immunofluorescence Study ◽  
Immunofluorescent Localization ◽  
Rabbit Igg ◽  
Semithin Sections ◽  
Filament Protein

In cultured skeletal muscle cells of chick, one intermediate filament protein, vimentin, is primarily formed and then synthesis of desmin follows. Coexistence of vimentin and desmin has been immunocytochemically confirmed in chick embryonic skeletal musclecells. Immunofluorescent localization of vimentin and desmin has been described in developing myocardial cells of hamster. However, initial localization of desmin and vimentin in early embryonic heart has not been reported in detail. By quick-freeze deep-etch method a loose network of intermediate filaments was revealed to exist surrounding myofibrils. In this report, immunocytochemical localization of desmin and vimentin is visualized in early stages of chick embryonic my ocardium.Chick embryos, Hamburger-Hamilton (H-H) stage 8 to hatch, and 1 day old postnatal chicks were used in this study. For immunofluorescence study, each embryo was fixed with 4% paraformaldehyde and embedded in Epon 812. De-epoxinized with sodium methoxide, semithin sections were stained with primary antibodies (rabbit anti-desmin antibody and anti-vimentin antibody)and secondary antibody (RITC conjugated goat-anti rabbit IgG).

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