250708-49-7

Upstream product

• 108-24-7 acetic anhydride 
• 250708-42-0 5-azido-3-O-benzyl-4-[(benzyloxy)methyl]-5-deoxy-1,2-O-(1-methylethylidene)-β-L-lyxofuranose 
• 100-39-0 benzyl bromide 
• 64-19-7 acetic acid 
• 263547-07-5 3-O-benzyl-4-[(benzyloxy)methyl]-1,2-O-(1-methylethylidene)-5-O-(trifluoromethylsulfonyl)-β-L-lyxofuranose 
• 153186-10-8 ((3aR,5R,6S,6aR)-6-(benzyloxy)-5-((benzyloxy)methyl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)methanol 
• 63593-03-3 1,2-O-isopropylidene-3-O-benzyl-4-hydroxymethyl-α-D-ribofuranose 

Downstream Products

• 250708-41-9 1-{2-O-acetyl-5-azido-3-O-benzyl-4-[(benzyloxy)methyl]-5-deoxy-α-L-lyxothranosyl}-5-methylpyrimidine-2,4-(1H,3H)-dione 
• 1361928-18-8 1-{2'-O-methyl-3'-O-[2-cyanoethoxy(diisopropylamino)phosphino]-4'-C-trifluoroacetylaminomethyl-5'-(4,4'-dimethoxytrityl)-β-D-ribofuranosyl}-N4-Isobutyrylcytosine 
• 1361928-16-6 1-[2'-O-methyl-4'-C-trifluoroacetylaminomethyl-5'-(4,4'-dimethoxytrityl)-β-D-ribofuranosyl]cytosine 
• 1391040-28-0 C₅₁H₅₈F₃N₃O₁₂S 
• 1361928-15-5 C₃₆H₃₆F₃N₃O₁₀ 
• 1361928-14-4 1-{2'-O-methyl-3'-O-[2-cyanoethoxy(diisopropylamino)phosphino]-4'-C-trifluoroacetylaminomethyl-5'-(4,4'-dimethoxytrityl)-β-D-ribofuranosyl}uracil 
• 1361928-13-3 1-[2'-O-methyl-4'-C-trifluoroacetylaminomethyl-5'-(4,4'-dimethoxytrityl)-β-D-ribofuranosyl]uracil 
• 1361928-11-1 1-(2'-O-methyl-3',5'-di-O-benzyl-4'-C-trifluoroacetylaminomethyl-β-D-ribofuranosyl)uracil 
• 1361928-10-0 1-(2'-O-methyl-3',5'-di-O-benzyl-4'-C-azidomethyl-β-D-ribofuranosyl)uracil 
• 1361928-08-6 1-(2'-O-methyl-3',5'-di-O-benzyl-4'-C-azidomethyl-β-D-ribofuranosyl)-3-(4-methoxybenzyl)uracil 
• 1361928-07-5 C₃₂H₃₃N₅O₇ 
• 1361928-06-4 1-(2'-O-acetyl-3',5'-di-O-benzyl-4'-C-azidomethyl-β-D-ribofuranosyl)-3-(4-methoxybenzyl)uracil 
• 1361928-05-3 1-(2'-O-acetyl-3',5'-di-O-benzyl-4'-C-azidomethyl-β-D-ribofuranosyl)uracil 

Relevant academic research and scientific papers

NUCLEOSIDE DERIVATIVE AND USE THEREOF

A nucleoside derivative represented below, or a salt thereof. (In (1), R1 represents a hydrogen atom, a hydroxyl group or a protected group, and in (2), X represent a halogen atom. In (1) and (2), R2 and R4 each represent

CROSSLINKED NUCLEIC ACID GUNA, METHOD FOR PRODUCING SAME, AND INTERMEDIATE COMPOUND

The present invention provides a method for producing guanidine crosslinked artificial nucleic acid (abbreviated hereinafter as GuNA), and an intermediate compound for the production thereof. Specifically, the present invention provides a method for producing a compound represented by general formula I: (in the formula, R1, R2, R3, R4, R5, R6, m and ring A are as defined in the specification) or a salt thereof wherein a reducing agent is reacted with a compound represented by general formula II: (in the formula, R1, R2, R3, R4, R5, R6, m, and ring A′ are as defined in the specification).

Synthesis, gene silencing, and molecular modeling studies of 4′- C -aminomethyl-2′- O -methyl modified small interfering RNAs

The linear syntheses of 4′-C-aminomethyl-2′-O-methyl uridine and cytidine nucleoside phosphoramidites were achieved using glucose as the starting material. The modified RNA building blocks were incorporated into small interfering RNAs (siRNAs) by employing solid phase RNA synthesis. Thermal melting studies showed that the modified siRNA duplexes exhibited slightly lower Tm (～1 °C/modification) compared to the unmodified duplex. Molecular dynamics simulations revealed that the 4′-C-aminomethyl- 2′-O-methyl modified nucleotides adopt South-type conformation in a siRNA duplex, thereby altering the stacking and hydrogen-bonding interactions. These modified siRNAs were also evaluated for their gene silencing efficiency in HeLa cells using a luciferase-based reporter assay. The results indicate that the modifications are well tolerated in various positions of the passenger strand and at the 3′ end of the guide strand but are less tolerated in the seed region of the guide strand. The modified siRNAs exhibited prolonged stability in human serum compared to unmodified siRNA. This work has implications for the use of 4′-C-aminomethyl-2′-O-methyl modified nucleotides to overcome some of the challenges associated with the therapeutic utilities of siRNAs.

Oligonucleotides containing novel 4'-C- or 3'-C-(aminoalkyl)-branched thymidines

The synthesis of four novel 3'-C-branched and 4'-C-branched nucleosides and their transformation into the corresponding 3'-O-phosphoramidite building blocks for automated oligonucleotide synthesis is reported. The 4'-C-branched key intermediate 11 was synthesized by a convergent strategy and converted to its 2-O-methyl and 2'-deoxy-2'-fluoro derivatives, leading to the preparation of novel oligonucleotide analogues containing 4'-C-(aminomethyl)-2'-O-methyl monomer X and 4'-C-(aminomethyl)-2'-deoxy-2'-fluoro monomer Y (Schemes 2 and 3). In general, increased binding affinity towards complementary single- stranded DNA and RNA was obtained with these analogues compared to the unmodified references (Table 1). The presence of monomer X or monomer Y in a 2'-O-methyl-RNA oligonucleotide had a negative effect on the binding affinity of the 2'-O-methyl-RNA oligonucleotide towards DNA and RNA. Starting from the 3'-C-allyl derivative 28, 3'-C-(3-aminopropyl)-protected nucleosides and 3'- O-phosphoramidite derivatives were synthesized, leading to novel oligonucleotide analogues containing 3'-C-(3-aminopropyl)thymidine monomer Z or the corresponding 3'-C-(3-aminopropyl)-2'-O,5-dimethyluridine monomer W (Schemes 4 and 5). Incorporation of the 2'-deoxy monomer Z induced no significant changes in the binding affinity towards DNA but decreased binding affinity towards RNA, while the 2'-O-methyl monomer Z induced decreased binding affinity towards DNA as well as RNA complements (Table 2).