3510-73-4Relevant academic research and scientific papers
METHOD FOR SYNTHESIZING DIVERSELY SUBSTITUTED PURINES
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Page/Page column 28; 23, (2018/12/03)
The present invention relates to a method for synthesizing diversely substituted purines starting from a pyrimidine. Formula (I). The method comprises the formation of an amidine group on the pyrimidine by implementing a Vilsmeier type reagent, the functi
A One-Pot Synthesis of Highly Functionalized Purines
Zelli, Renaud,Zeinyeh, Wa?l,Haudecoeur, Romain,Alliot, Julien,Boucherle, Benjamin,Callebaut, Isabelle,Décout, Jean-Luc
, p. 6360 - 6363 (2017/12/08)
Highly substituted purines were synthesized in good to high yields through a one-pot straightforward metal-free scalable method, using the Traube synthesis adapted to Vilsmeier-type reagents. From 5-amino-4-chloropyrimidines, new 9-aryl-substituted chloropurines and intermediates for peptide nucleic acid synthesis were prepared. Variant procedures allowing a rapid synthesis of ribonucleosides and 7-benzylpurine from 5-amidino-6-aminopyrimidines are also reported to illustrate the high potential of this versatile toolbox. This route appears to be particularly interesting in the field of nucleic acids for a direct and rapid access to various new 8-alkylpurine nucleosides.
High-throughput five minute microwave accelerated glycosylation approach to the synthesis of nucleoside libraries
Bookser, Brett C.,Raffaele, Nicholas B.
, p. 173 - 179 (2007/10/03)
The Vorbrueggen glycosylation reaction was adapted into a one-step 5 min/130 °C microwave assisted reaction. Triethanolamine in acetontrile containing 2% water was determined to be optimal for the neutralization of trimethylsilyl inflate allowing for direct MPLC purification of the reaction mixture. When coupled with a NH3/methanol deprotection reaction, a high-throughput method of nucleoside library synthesis was enabled. The method was demonstrated by examining the ribosylation of 48 nitrogen containing heteroaromatic bases that included 25 purines, four pyrazolopyrimidines, two 8-azapurines, one 2-azapurine, two imidazopyridines, two benzimidazoles, three imidazoles, three 1,2,4-triazoles, two pyrimidines, two 3-deazapyrimidines, one quinazolinedione, and one alloxazine. Of these, 32 yielded single regioisomer products, and six resulted in separable mixtures. Seven examples provided inseparable regioisomer mixtures of -two to three compounds (16 nucleosides), and three examples failed to yield isolable products. For the 45 single isomers isolated, the average two-step overall yield ± SD was 26 ± 16%, and the average purity ± SD was 95 ± 6%. A total of 58 different nucleosides were prepared of which 15 had not previously been accessed directly from glycosylation/deprotection of a readily available base.
Synthesis, Biological Activity and Molecular Modeling of 6-Benzylthioinosine Analogues as Subversive Substrates of Toxoplasma gondii Adenosine Kinase
Yadav, Vikas,Chu, Chung K.,Rais, Reem H.,Al Safarjalani, Omar N.,Guarcello, Vincenzo,Naguib, Fardos N. M.,El Kouni, Mahmoud H.
, p. 1987 - 1996 (2007/10/03)
Toxoplasma gondii is the most common cause of secondary CNS infections in immunocompromised persons such as AIDS patients. The major route of adenosine metabolism in T. gondii is direct phosphorylation to adenosine 5′-monophosphate (AMP) catalyzed by the enzyme adenosine kinase (EC 2.7.1.20). Adenosine kinase in T. gondii is significantly more active than any other purine salvage enzyme in this parasite and has been established as a potential chemotherapeutic target for the treatment of toxoplasmosis. Subversive substrates of T. gondii, but not the human, adenosine kinase are preferentially metabolized to their monophosphorylated forms and become selectively toxic to the parasites but not their host. 6-Benzylthioinosine (BTI) was identified as an excellent subversive substrate of T. gondii adenosine kinase. Herein, we report the synthesis of new analogues of BTI as subversive substrates for T. gondii adenosine kinase. These new subversive substrates were synthesized starting from tribenzoyl protected D-ribose. To accomplish the lead optimization process, a divergent and focused combinatorial library was synthesized using a polymer-supported trityl group at the 5′-position. The combinatorial library of 20 compounds gave several compounds more active than BTI. Structure-activity relationship studies showed that substitution at the para position plays a crucial role. To investigate the reasons for this discrimination, substrates with different substituents at the para position were studied by molecular modeling using Monte Carlo Conformational Search followed by energy minimization of the enzyme-ligand complex.
Introduction of a benzoyl group onto riboside in aqueous solution: One- step synthesis of 6-chloropurine 2',3'-di-O-benzoylriboside
Kozai, Shigetada,Takamatsu, Satoshi,Izawa, Kunisuke,Maruyama, Tokumi
, p. 4355 - 4358 (2007/10/03)
A benzoyl group was introduced onto the 3'-hydroxyl group of 6- chloropurine riboside by treatment with benzoylating agents in the presence of an organic or inorganic base in aqueous solution, in which further reaction gave 6-chloropurine 2',3'-di-O-benzo
A New Direct Glycosylation of Pyrimidine, Pyrazole, Imidazole and Purine Heterocycles via their N-tetrahydropyranyl (THP) Derivatives
Manfredini, Stefano,Baraldi, Pier Giovanni,Bazzanini, Rita,Guarneri, Mario,Simoni, Daniele
, p. 583 - 584 (2007/10/02)
Pyrimidine, pyrazole, imidazole and purine N-tetrahydropyranyl (THP) derivatives have been converted in one-pot and in a regio- and stereo-selective manner into the corresponding β-D-2',3',5'-tri-O-benzoyl ribofuranosyl nucleoside derivatives on treatment with 1-β-acetyl-2',3',5'-tri-O-benzoyl-ribofuranose, hexamethyldisilazane (HMDS), trimethylsilyl chloride (TMSCl), and trimethylsilyl triflate (TMST).
Synthesis of 3'-fluoro-3'-deoxy-N6-cyclopentyladenosine
Ceulemans,Busson,Weyns,Vandendriessche,Rozenski,Ijzerman,Herdewijn
, p. 1991 - 2000 (2007/10/02)
Starting from 9-(β-D-xylofuranosyl)-6-chloropurine, the title compound was prepared in four steps. Reaction with cyclopentylamine followed by treatment of the 2'-O,5'-O-ditritylated material with diethylaminosulfur trifluoride (DAST), yielded after deprot
Pentenyl Ribosides: New Reagents for Purine Nucleoside Synthesis
Chapeau, Marie-Christine,Marnett, Lawrence J.
, p. 7258 - 7262 (2007/10/02)
Protected pent-4-enyl ribosides and deoxyribosides were synthesized as reagents for the preparation of nucleosides and deoxynucleosides.Reaction of pent-4-enyl 2',3',5'-tri-O-benzoyl-D-erythro-pentofuranoside with five nucleobases in the presence of N-iod
Partial Protection of Carbohydrate Derivatives. Part 4. Regioselective 2'-O-Deacylation of Fully Acylated Purine and Pyrimidine Ribonucleosides with Hydroxylaminium Acetate
Ishido, Yoshiharu,Sakairi, Nobuo,Okazaki, Kei,Nakazaki, Nobuo
, p. 563 - 573 (2007/10/02)
Like hydrazine hydrate, hydroxylamine was found to be useful for the regioselective 2'-O-deacylation of fully acylated purine and pyrimidine ribonucleosides as its salt with acetic acid; the partial O-deacylation reactions (which were not accompanied by undesirable discolouration as happens with hydrazine hydrate) gave the corresponding di-O-acylribonucleosides in superior yields; e.g. 2',3'-di-O-benzoyladenosine (74percent yield), 3',5'- (64percent yield) and 2',5'-di-O-benzoyl-N6-benzyladenosine (63percent yield on performing the reaction in ethanol), N2,3',5'-tri-O-benzoylguanosine (66percent yield), N2,2',5'-tri-isobutyrylguanosine (48percent yield), and 3',5'-di-O-benzoyluridine (61percent yield) were obtained using hydroxylaminium acetate in pyridine.Treatment of fully acetylated ribonucleosides with an excess of hydroxylaminium acetate gave the corresponding 5'-O-acetylribonucleosides in quantitative yields.The excellent regioselectivity observed in the present partial O-decyclation was confirmed on the basis of chromatographic separation; the mixtures of di-O-acylribonucleosides, which had already been equilibrated in pyridine, were re-equilibrated on the silica gel during separation, e.g. a 70 : 30 mixture of 3',5'- and 2',5'-di-O-benzoyladenosine was completely converted into the former based on 1H n.m.r spectroscopy.The acetates of 9-β-D-xylo- and -arabino-furanosyladenine were also found to give predominantly the corresponding 3',5'-diacetates on hydroxylaminolysis.
The preparation of 14C-Labeled Ribosyl-trans-zeatin and Its cis Isomer
Nakajima, Hiromitsu,Yokota, Takao,Watanabe, Naoharu,Takahashi, Nobutaka
, p. 2717 - 2720 (2007/10/02)
14C-Labeled ribosyl-trans-zeatin and its cis isomer have been prepared from inosine by facile reactions.
