- A method for synthesizing nelarabine
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The invention discloses a new method for synthesizing nelarabine. According to the new method for synthesizing nelarabine, vidarabine is taken as a raw material, and acetylization, methoxylation, nitration and reduction reactions are carried out, so that the target product nelarabine is obtained with the total yield of 52%. The new method for synthesizing nelarabine has the greatest advantages that all the prepared nelarabine is beta configuration, and a tedious step of separating isomers in the traditional method is omitted; meanwhile, the raw material is a common chemical material, so that the raw material is available; and the operation is simple and convenient, the column chromatography isolation is not needed to be carried out in the whole course, and industrialization and expanded production are easy to realize.
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Paragraph 0027; 0028
(2018/02/22)
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- Selective Acylation of Nucleosides, Nucleotides, and Glycerol-3-phosphocholine in Water
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A convenient selective synthesis of 2′,3′-di-O-acetyl-nucleotide-5′-phosphates, 2′,3′-di-O-acetyl-nucleotide-5′-triphosphates and 2′,3′,5′-tri-O-acetyl-nucleosides in water has been developed. Furthermore, a long-chain selective glycerol-3-phosphocholine diacylation is elucidated. These reactions are environmentally benign, rapid, high yielding, and the products are readily purified. Importantly, this reaction may indicate a prebiotically plausible reaction pathway for the selective acylation of key metabolites to facilitate their incorporation into protometabolism.
- Fernández-García, Christian,Powner, Matthew W.
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supporting information
p. 78 - 83
(2016/12/26)
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- Synthesis of nelarabine with pure β-anomer through late-stage C-H nitration/nitro-reduction
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An efficient and pure β-anomer synthesis of the clinical drug nelarabine from the readily available vidarabine has been achieved for the first time. The C6 amino group of vidarabine was transformed to methoxy group by diazotization/chlorination followed by methoxylation using Na2CO3/MeOH system. The formation of C(2)-N bond was achieved via the highly selective C-H bond functionalization by reacting with 2,2,2-trifluoroacetic anhydride (TFAA) and tetrabutylammonium nitrate. The final product was obtained in total yield of 58.6% by 5 steps-synthesis from vidarabine after the reduction of nitro group to amino group. Moreover, the drug nelarabine could be obtained in 100 grams scale successfully and no chromatography was needed, which made this route more attractive for industrial application.
- Xia, Ran,Sun, Li-Ping,Qu, Gui-Rong
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p. 2386 - 2393
(2016/03/01)
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- Application of the dipeptidyl peptidase IV (DPPIV/CD26) based prodrug approach to different amine-containing drugs
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Here we explore the applicability of the dipeptidyl peptidase IV (DPPIV/CD26) based prodrug approach to a variety of amine-containing drugs. Efficient procedures have been developed for the synthesis of dipeptide and tetrapeptide amide prodrugs including
- Diez-Torrubia, Alberto,García-Aparicio, Carlos,Cabrera, Silvia,De Meester, Ingrid,Balzarini, Jan,Camarasa, María-José,Velázquez, Sonsoles
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scheme or table
p. 559 - 572
(2010/06/16)
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- Enzymatic regioselective and complete deacetylation of two arabinonucleosides
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Candida antarctica lipase B (CAL-B)-catalysed regioselective deacetylation of 2′,3′,5′-tri- O-acetyl-1-β- d-arabinofuranosyluracil (1) and 2′,3′,5′-tri- O-acetyl-9-β- d-arabinofuranosyladenine (2) was studied. The choice of the reaction medium allowed the regioselective formation of products bearing different degree of acetylation: in isopropanol, CAL-B catalysed the formation of the corresponding 2′- O-acetylated arabinonucleosides, while hydrolyses afforded the 2′,3′-di- O-acetylated products. In particular, the procedure herein described allows a simple and efficient preparation of the reported vidarabine prodrug 2′,3′-di- O-acetyl-9-β- d-arabinofuranosyladenine, avoiding the utilisation of protective groups. Moreover, to achieve full deacetylation of the assayed substrates, a set of commercial hydrolases and fungal keratinases from Doratomyces microsporus (DMK) and Paecilomyces marquandii (PMK) were tested. While only PMK and DMK catalysed the quantitative complete deacetylation of 1, DMK accomplished full deacetylation of 2 in shorter time than the other assayed enzymes.
- Sabaini, Maria B.,Zinni, Maria A.,Mohorcic, Martina,Friedrich, Jozefa,Iribarren, Adolfo M.,Iglesias, Luis E.
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experimental part
p. 225 - 229
(2010/11/02)
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- A versatile synthesis of 5'-fenctionalized nucleosides through regioselective enzymatic hydrolysis of their peracetylated precursors
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We describe a chemo-enzymatic synthesis of modified nucleosides through lipase-catalyzed hydrolysis of their peracetylated precursors. It was found from screening of a large number of substrates that these enzymesregioselectivities were affected by the sugar and the nucleobase structures. By selecting the best enzyme for each substrate in terms of activity and regioselectivity, we prepared a small library of differently monodeprotecled purine and pyrimidine nucleosides useful as intermediates for the synthesis of high-value nucleosides and mononucleotides. By this approach, the chemo-enzymatic preparation of doxifluridine (14) and uridine 5'-monophosphate (5'-UMP, 15) from peracetylated uridine 1 was carried out. Elimination of many of the processing stages associated with existing methods was achieved, and higher yields and products of increased purity were generated. Wiley-VCH Verlag GmbH & Co. KGaA.
- Bavaro, Teodora,Rocchietti, Silvia,Ubiali,Filice, Marco,Terreni, Marco,Pregnolato, Massimo
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experimental part
p. 1967 - 1975
(2009/09/08)
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- Nucleic acid related compounds. 127. Selective N-deacylation of N,O-peracylated nucleosides in superheated methanol
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Solutions of peracylated adenosine, cytidine, and related nucleoside derivatives undergo selective N-deacylation upon heating at elevated temperatures (oil bath ≥ 105 °C) in methanol. An increase in the bulk of the N-acyl group has little effect on the rate of N-deacylation but increases the N/O selectivity ratio. Extended heating is required for N-deacylation with arylcarboxylic acid derivatives. Contamination with acidic or basic reagent residues is avoided.
- Nowak, Ireneusz,Conda-Sheridan, Martin,Robins, Morris J.
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p. 7455 - 7458
(2007/10/03)
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