91592-66-4

Upstream product

• 4836-13-9 N₄-benzoyl-2'-deoxycytidine 
• 647834-80-8 O-levulinyl acetonoxime 
• 40608-06-8 levulinic anhydride 
• 591-12-8 5-methyl-2-furanone 
• 123-76-2 levulinic acid 
• 67219-55-0 4-N-Benzoyl-2'-deoxy-5'-O-(4,4'-dimethoxytrityl)cytidine 
• 93134-38-4 (2R,3S,5R)-5-(4-benzamido-2-oxopyrimidin-1(2H)-yl)-2-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)tetrahydrofuran-3-yl-4-oxopentanoate 

Downstream Products

• 224186-73-6 C₅₅H₅₇N₆O₁₅P 
• 402920-18-7 C₅₉H₆₂N₉O₁₅P 
• 262429-99-2 4-oxo-pentanoic acid 5-(4-benzoylamino-2-oxo-2H-pyrimidin-1-yl)-2-[{5-(6-benzoylamino-purin-9-yl)-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-tetrahydro-furan-3-yloxy}-(2-cyano-ethoxy)-thiophosphoryloxymethyl]-tetrahydro-furan-3-yl ester 
• 91592-67-5 C₈₈H₇₉Cl₂N₁₃O₂₁P₂ 
• 863507-30-6 C₅₉H₆₂N₉O₁₅PS 
• 224186-63-4 C₅₀H₅₁N₆O₁₃PS 
• 199436-72-1 4-Oxo-pentanoic acid (2R,3S,5R)-5-(4-benzoylamino-2-oxo-2H-pyrimidin-1-yl)-2-[[(2R,3S,5R)-5-(6-benzoylamino-purin-9-yl)-2-hydroxymethyl-tetrahydro-furan-3-yloxy]-(4-chloro-phenylsulfanyl)-phosphoryloxymethyl]-tetrahydro-furan-3-yl ester 
• 199436-67-4 C₆₅H₆₀ClN₈O₁₄PS 

Relevant academic research and scientific papers

On the formation of longmers in phosphorothioate oligodeoxyribonucleotide synthesis

The extent of longmer formation in phosphorothioate oligodeoxyribonucleotide synthesis through amidite chemistry on solid support depends on base composition, contact time and acidity of the promoter used for activation of the phosphoramidite. A longmer f

Process Development of Biocatalytic Regioselective 5′-O-Levulinylation of 2′-Deoxynucleosides

An enzymatic process was optimized for regioselective levulinylation of the 5′-hydroxyl group in 2′-deoxynucleosides. The results revealed that the nucleobase protecting group influenced the successful outcome of the enzymatic reaction. The enhanced solubility of 4-tert-butylphenoxyacetyl protected 2′-deoxynucleoside played a major role during acylation reaction enabling the starting nucleosides to be the best substrates for Candida antarctica lipase B. Furthermore, we have developed a packed column protocol as a superior alternative to batch process carried-out in a flask, particularly when scale-up is required. The industrial application of this method was demonstrated via the synthesis of 5′-O-levulinylthymidine on a 25 g scale.

CAL-B-catalyzed acylation of nucleosides and role of the sugar conformation: An improved understanding of the enzyme-substrate recognition

We demonstrate that the sugar ring conformation of nucleosides plays a critical role during Candida antarctica lipase B (CAL-B) catalyzed acylation. Specifically, the North (N), but not the South (S) nucleoside sugar ring conformation is preferred for efficient binding at the catalytic site. In this study, we used nuclear magnetic resonance (NMR) spectroscopy experiments to establish the sugar ring conformation of nucleosides and performed molecular modeling studies to support the observations. The ribo-and 2'-substituted (OMe, F) nucleosides displaying the N-conformation undergo rapid and facile acylation compared to the 2'-deoxynucleosides with the S-conformation. This study improves our understanding of the critical role that sugar conformation plays in enzyme-substrate recognition during biotransformations using CAL-B. To the best of our knowledge, this is the first experimental report offering a rationale for the observed selectivity during acylation of nucleosides containing the N-sugar conformation.

Enzymatic parallel kinetic resolution of mixtures of d / l 2′-deoxy and ribonucleosides: An approach for the isolation of β- L -nucleosides

We have developed a lipase-catalyzed parallel kinetic resolution of mixtures of β-d/l-nucleosides. The opposite selectivity during acylation exhibited by Pseudomonas cepacia lipase (PSL-C) with β-d- and β-l-nucleosides furnished acylated compounds that have different R f values. As a consequence, isolation of both products was achieved by simple column chromatography. Computer modeling of the transition-state analogues during acylation of β-d- and β-l-2′-deoxycytidine with PSL-C was carried out to explain the high selectivity. PSL-C favored the 3′-O-levulination of the β-d enantiomer, whereas the 5′-OH group was acylated in 2′-deoxy-β-l-cytidine. In both cases, the cytosine base was placed in the alternate hydrophobic pocket of PSLs substrate-binding site, where it can form extra hydrogen bonds (in addition to the five essential catalytically relevant hydrogen bonds) that stabilize these intermediates catalyzing the selective acylation of β-d/l-nucleosides.

2,2,5,5-Tetramethylpyrrolidin-3-one-1-sulfinyl group for 5′-hydroxyl protection of deoxyribonucleoside phosphoramidites in the solid-phase preparation of DNA oligonucleotides

Several nitrogen-sulfur reagents have been investigated as potential 5′-hydroxyl protecting groups for deoxyribonucleoside phosphoramidites to improve the synthesis of oligonucleotides on glass microarrays. Out of the nitrogen-sulfur-based protecting grou

Novel enzymatic synthesis of levulinyl protected nucleosides useful for solution phase synthesis of oligonucleotides

An efficient synthesis of 3′- and 5′-O-levulinyl-2′- deoxy- and 2′-O-alkylribonucleosides has been developed from appropriate nucleosides by enzyme-catalyzed regioselective acylation in organic solvents. Several lipases were screened in combination with a

Direct regioselective enzymatic acylation of nucleosides: Building-blocks for the solution phase synthesis of oligonucleotides

The synthesis of 3′- and 5′-O-levulinyl nucleosidic monomers through enzymatic acylation with acetonoxime levulinate is demonstrated. The acylation process takes place in one-step and use of expensive reagents, such as DMTrCl is avoided. The regioselectiv

Oligodeoxyribonucleotide phosphorothioates: Substantial reduction of (N- 1)-mer content through the use of trimeric phosphoramidite synthons

Use of fully protected trimeric phosphoramidite synthons in the synthesis of oligonucleotide phosphorothioate shows a substantial reduction (>85%) in (n-1)-mer content as compared to oligomers synthesized through coupling of standard phosphoramidite monom

The H-phosphonate approach to the synthesis of oligonucleotides and their phosphorothioate analogues in solution

A new approach to the synthesis of oligonucleotides and oligonucleotide phosphorothioates in solution is described; it is based on H-phosphonate coupling [with bis(2-chlorophenyl) phosphorochloridate 22 as the coupling agent] at -40 deg C, followed by in situ sulfur transfer involving either 2-(4-chlorophenylsulfanyl)isoindole-1,3(2H)-dione 23a or 4-[(2-cyanoethyl)sulfanyl]morpholine-3,5-dione 26. The yields of the coupling and sulfur transfer reactions are virtually quantitative and, following unblocking by previously reported procedures, very pure products (d[ApC], d[TpGpApC], d[TpGp(s)ApC], d[Gp(s)A] and d[Cp(s)Tp(s)Gp(s)A]) are obtained.

Improvements in Oligodeoxyribonucleotide Synthesis: Methyl N,N-Dialkylphosphoramidite Dimer Units for Solid Support Phosphite Methodology

Two procedures for the synthesis of methyl N,N-dialkylphosphoramidite dinucleotides (dimer units) compatible with the current solid support phosphite methodology of oligodeoxynucleotide synthesis are described for the first time.In the first procedure a c