Modification of the 5' position of purine nucleosides. 1. Synthesis and biological properties of alkyl adenosine-5'-carboxylates

Prasad, Raj Nandan; Fung, Anthony K. L.; Tietje, Karin; Stein, Herman H.; Brondyk, Harold D.

doi:10.1021/jm00232a003

Cited by 23 publications

(15 citation statements)

References 9 publications

(31 reference statements)

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“…mp 145−148 °C); MS m/z 337 (M + )], isobutyl ester 4b [23%; mp 181−183 °C (lit . mp 178−180 °C); MS m/z 337 (M + )], and 2-chloroethyl ester 6b [49%; mp 205−208 °C (lit . mp 208−210 °C); MS m/z 343 (M + , 35 Cl)] were prepared with the respective alcohols by the procedure for 5b .…”

Section: Methodsmentioning

confidence: 99%

“…Adenosine-5 ‘ -( N,N- diethylcarboxamide) (14b). Treatment of 1a (160 mg, 0.5 mmol) with thionyl chloride (0.50 mL, 0.81 mg, 6.8 mmol) and DMF (2 drops) gave the acid chloride 13a as described . Et 2 NH (1 mL) was added dropwise at 0 °C to this 13a in THF (2 mL), and stirring was continued at ambient temperature for 2 h. The solution was evaporated, the residue was partitioned (HCl/H 2 O/CHCl 3 ), and the organic layer was washed (NaHCO 3 /H 2 O, brine), dried (MgSO 4 ), and evaporated to give 14a (yellow oil).…”

Section: Methodsmentioning

confidence: 99%

“…Oxidation of 2′,3′-O-isopropylideneadenosine with potassium permanganate 21 gave more reliable yields of 2′,3′-O-isopropylideneadenosine-5′-carboxylic acid (1a; 83%) than recently described procedures. 22 Treatment of 1a with diazomethane gave methyl ester 2a 23 (92%), and treatment of 1a and 2a with aqueous trifluoroacetic acid (TFA) gave Ado-5′-carboxylic acid 23 (1b) and its methyl ester 16,17 2b (Scheme 1). Treatment of 1b with thionyl chloride and the alcohol 16,17 gave butyl (3b), isobutyl (4b), benzyl (5b), and 2-chloroethyl (6b) esters.…”

Section: Chemistrymentioning

confidence: 99%

“…2b We now report studies designed to further investigate the 5′-hydrolytic potential of AdoHcy hydrolase with 5′-modified analogues derived from Ado-5′-carboxylic acid. A number of studies on the binding of Ado-5′-carboxylic (uronic) acid ester 16,17 and amide [18][19][20] derivatives with adenosine receptors have been reported. [18][19][20]…”

Section: Introductionmentioning

confidence: 99%

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Inactivation of S-Adenosyl-l-homocysteine Hydrolase by Amide and Ester Derivatives of Adenosine-5‘-carboxylic Acid

et al. 1996

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S-Adenosyl-L-homocysteine (AdoHcy) hydrolase has been shown to have (5'/6') hydrolytic activity with vinyl (5') or homovinyl (6') halides derived from adenosine (Ado). This hydrolytic activity is independent of its 3'-oxidative activity. The vinyl (or homovinyl) halides are converted into 5'(or 6')-carboxaldehydes by the hydrolytic activity of the enzyme, and inactivation occurs via the oxidative activity. Amide and ester derivatives of Ado-5'-carboxylic acid were prepared to further probe the hydrolytic capability of AdoHcy hydrolase. The oxidative activity (but not the hydrolytic activity) is involved in the mechanism of inhibition of the enzyme by the ester and amide derivatives of Ado-5'-carboxylic acid, in contrast to the inactivation of this enzyme by adenosine-derived vinyl or homovinyl halide analogues during which both activities are manifested.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Chemistrymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Inactivation of S-Adenosyl-l-homocysteine Hydrolase by Amide and Ester Derivatives of Adenosine-5‘-carboxylic Acid

et al. 1996

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“…Uronic acid, uronate, or uronamide‐based nucleosides bearing pyrimidine,10 uracil,11 cytosine,11 and purine,12–15 moieties have been synthesized, and some of these compounds were found to have significant biological activities. Methods for their synthesis involve the N ‐glycosylation of silylated nucleobases with glucuronyl donors such as glycosyl halides, 1‐ O ‐acetyl donors,11b,12 or methyl glycosides,15 and the oxidation of the C‐5′ hydroxy group of nucleosides 11c,16. Among the reported biologically active compounds, 2‐acetamido‐6‐chloropurine nucleosides containing a bicyclic uronate moiety were found to be cholinesterase (ChE) inhibitors, with high degrees of inhibition and high selectivities towards butyrylcholinesterase (BChE) 15.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Purine Nucleosides from D‐Glucuronic Acid Derivatives and Evaluation of Their Cholinesterase‐Inhibitory Activities

et al. 2014

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Glucuronolactones were used as precursors for N9 and N7 purine nucleosides containing glucuronic acid derivatives in their structures. Acetylated N‐benzylglucofuran‐ and glucopyranuronamides were synthesized in a few steps from glucofuranurono‐6,3‐lactone. They were converted into the corresponding furanosyl and pyranosyl uronamide‐based nucleosides by N‐glycosylation with silylated 2‐acetamido‐6‐chloropurine in the presence of trimethylsilyl triflate. The triacetylated bicyclic lactone was coupled itself with the nucleobase to give bicyclic N9,N7 nucleosides. Tri‐O‐acetylglucopyranurono‐6,1‐lactone was used for the first time as a glycosyl donor for N‐glycosylation, and led to β‐configured N9‐ and N7‐linked purinylglucuronides under reaction conditions similar to those used with the 1‐O‐acetyl‐substituted glycosyl donors. The cholinesterase inhibitory profiles of the synthetic nucleosides bearing glucuronic acid derivatives as glycons were evaluated, and they showed moderate selective acetylcholinesterase inhibitory activities (Ki = 14.78–50.53 μM). The best inhibition was shown by the furanosyl N9‐linked uronamide‐based purine nucleoside.

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Synthese und Eigenschaften von 5′‐Desoxynucleosid‐5′‐carbonsäuren und ihren Derivaten

Meyer

Follmann

1980

Chem. Ber.

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Die Darstellung von bisher nicht allgemein zuganglichen 5'-Desoxynucleosid-5'-carbonitrilen (3) gelingt sowohl in der Ribo-wie 2'-Desoxyribonucleosidreihe, wenn man Nucleosid-S'-tosylate mit festem KCN unter Kronenether-Katalyse in organischen Lbsungsmitteln umsetzt. Auch d,5'-Cyclopyrimidinnucleoside eignen sich als Ausgangsmaterial. Aus den Nitrilen 3 sind unter vorzugsweise sauren Reaktionsbedingungen die Ester 6 und aus ihnen die S'-Desoxynucleosid-S'-carbonsauren (7) erhaltlich, die sich als Nucleotid-Modelle in biochemischen Systemen eignen. In alkalischer Losung erleiden die Nitrile 3 rasche Eliminierung der Purin-oder Pyrimidinbase. Aus dem Adeninnucleosid 3 a entsteht dabei ferner unter Addition des ungesattigten Zuckerfragmentes 10 das a n N6 zu einem Pyrrolidin modifizierte Nucleosid 12. Wie in anderen C-5'-modifizierten Nucleosiden zeigen die Circulardichroismus-Spektren der neuen Verbindungen eine starke elektronische Wechselwirkung zwischen polaren C-5'-Substituenten und den Chromophoren an. Synthesis and Properties of 5'-Deoxynucleoside 5'-Carboxylic Acids and DerivativesA preparative route to 5'-deoxynucleosid-5'-carbonitriles (3), both of the ribose and deoxyribose series, involves crown ether-catalyzed reaction of nucleoside S'-tosylates with solid potassium cyanide in organic solvents. d,S'-Cyclo derivatives of pyrimidine nucleosides can also serve as starting materials. The nitriles 3 require acidic conditions for conversion to the esters 6 of 5'-deoxynucleoside S'-carboxylic acids (7) which are suitable nucleotide models for biochemical studies. In alkaline solutions compounds 3 undergo rapid elimination of the purine or pyrimidine base. Furthermore the adenine derivative 3a, under addition of the unsaturated sugar fragment 10 yields a new nucleoside 12 in which N6 is inserted in a pyrrolidine ring. The circular dichroism spectra of the new compounds reflect strong electronic interaction between polar C-S'-substituents and the chromophores and are in line with those of other C-5'-modified nucleosides.Nucleoside und Nucleotide mit Strukturmodifikationen am exocyclischen C-5'-Atom haben zur Untersuchung der Spezifitat und Mechanismen von Enzymen des Nucleotidstoffwechselsl -4), der Molekulkonformationen und intramolekularen Wech~elwirkungens,~) und in Einzelfallen auch durch ihre pharmakologische Wirkung7.8) Bedeutung erlangt. Besonders interessieren Carboxylgruppen tragende Verbindungen, die den Phosphatrest der natiirlichen Nucleotide zu simulieren vermogen. Dabei hat sich gezeigt, daR die aus Nucleosiden durch Oxidation der terminalen CH;!OH-Gruppe einfach zuganglichen Nucleosid-5'-uronsauren als Modellsubstanzen i. allg. wenig befriedigen, weil in ihnen die Molekiilteile starr fixiert sind9J0). Die Substitution von C-5' durch weitere C-Atome, d. h. eine direkte Kettenverlangerung von Nucleosiden zu Derivaten der homologen Hexo-oder Heptofuranoside ist jedoch bisher nur in Ausnahmefallen g e l~n g e n~,~ -j3). In dieser Arbeit beschreiben wir eine offenbar allgemein anwendbare Reaktion,

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Modification of the 5' position of purine nucleosides. 1. Synthesis and biological properties of alkyl adenosine-5'-carboxylates

Cited by 23 publications

References 9 publications

Inactivation of S-Adenosyl-l-homocysteine Hydrolase by Amide and Ester Derivatives of Adenosine-5‘-carboxylic Acid

Inactivation of S-Adenosyl-l-homocysteine Hydrolase by Amide and Ester Derivatives of Adenosine-5‘-carboxylic Acid

Synthesis of Purine Nucleosides from D‐Glucuronic Acid Derivatives and Evaluation of Their Cholinesterase‐Inhibitory Activities

Synthese und Eigenschaften von 5′‐Desoxynucleosid‐5′‐carbonsäuren und ihren Derivaten

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