81691-06-7

Usage

Uses

Used in Biotechnology and Pharmaceutical Industry:
3-Methylpseudouridine is used as a stabilizing agent for increasing the viability or longevity of organs or organ explants by enhancing the stability and translational efficiency of modified mRNAs encoding proteins essential for organ survival.
Used in mRNA Therapeutics and Vaccines:
3-Methylpseudouridine is utilized as a key component in the development of mRNA-based therapeutics and vaccines, where it contributes to the improved performance and safety of these treatments by enhancing mRNA stability and reducing the risk of immune-related adverse effects.

Synthesis

ψ-Uridine was trimethylsilylated and the crude product was treated with acetyl chloride, to give the 1-acetyl derivative (3). Crude 3 was methylated with dimethoxymethyldimethylamine and then saponified, to give crystalline 3-methyl-ψ-uridine in 82% overall yield.

InChI:InChI=1/C10H14N2O6/c1-12-9(16)4(2-11-10(12)17)8-7(15)6(14)5(3-13)18-8/h2,5-8,13-15H,3H2,1H3,(H,11,17)

Upstream product

• 81691-05-6 1-Acetyl-5-((2S,3S,4R,5R)-3,4-bis-trimethylsilanyloxy-5-trimethylsilanyloxymethyl-tetrahydro-furan-2-yl)-3-methyl-1H-pyrimidine-2,4-dione 
• 482643-88-9 3-methyl-1-pivaloyloxymethyl-3',5'-O-(1,1,3,3-tetraisopropyl-1,3-disiloxanediyl)pseudouridine 
• 482643-86-7 3-methyl-1-pivaloyloxymethyl-3',5'-O-(1,1,3,3-tetraisopropyl-1,3-disiloxanediyl)-2'-O-(trimethylsilyl)pseudouridine 
• 482643-84-5 1-pivaloyloxymethyl-3',5'-O-(1,1,3,3-tetraisopropyl-1,3-disiloxanediyl)-2'-O-(trimethylsilyl)pseudouridine 
• 81691-04-5 1-acetyl-2',3',5'-tri-O-trimethylsilyl-ψ-uridine 
• 164300-60-1 3',5'-O-(1,1,3,3-tetraisopropyl-1,3-disiloxanediyl)-2'-O-(trimethylsilyl)pseudouridine 
• 1445-07-4 pseudouridine 
• 80545-49-9 3',5'-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)pseudouridine 
• 81691-07-8 3-methyl-3',5'-O-(1,1,3,3-tetraisopropyl-1,3-disiloxanediyl)pseudouridine 

Downstream Products

• 81691-10-3 2'-deoxy-3-methyl-ψ-uridine 

Relevant academic research and scientific papers

Synthesis of helix 69 of Escherichia coli 23S rRNA containing its natural modified nucleosides, m(3)Psi and Psi.

The synthesis of 3-methylpseudouridine (m(3)Psi) phosphoramidite, 5'-O-[benzhydryloxybis(trimethylsilyloxy)silyl]-2'-O-[bis(2-acetoxyethoxy)methyl]-3-methylpseudouridine-3'-(methyl-N,N-diisopropyl)phosphoramidite, is reported. Selective pivaloyloxymethyl protection of the Psi N1 followed by methylation at N3 was used to generate the naturally occurring pseudouridine analogue. The m(3)Psi phosphoramidite was used in combination with pseudouridine (Psi) and standard base phosphoramidites to synthesize a 19-nucleotide RNA representing helix 69 of Escherichia coli 23S ribosomal RNA (rRNA) (residues 1906-1924), containing a single m(3)Psi at position 1915 and two Psi's at positions 1911 and 1917. Our synthesis of the fully modified helix 69 RNA demonstrates the ability to make milligram quantities of RNA that can be used for further high-resolution structure studies. Site-selective introduction of the methyl group at the N3 position of pseudouridine at position 1915 causes a slight increase in the thermodynamic stability of the RNA hairpin relative to pseudouridine; RNAs containing either uridine or 3-methyluridine at position 1915 have similar stability. One-dimensional imino proton NMR and circular dichroism spectra of the modified RNAs reveal that the methyl group does not cause any substantial changes in the RNA hairpin structure.

Synthesis of 3-methylpseudouridine and 2'-deoxy-3-methyl-pseudouridine.

The first chemical synthesis of 3-methyl-psi-uridine (5) and its 2'-deoxy analogue (9) has been achieved. psi-Uridine was trimethylsilylated and the crude product was treated with acetyl chloride, to give the 1-acetyl derivative (3). Crude 3 was methylated with dimethoxymethyldimethylamine and then saponified, to give crystalline 5 in 82% overall yield. Treatment of 5 with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane afforded the 3'5'-protected product, which was converted into the 2'O-[(imidazol-1-yl) thiocarbonyl] derivative 7. Reduction of 7 with tributyltin hydride followed by deblocking of the product gave crystalline 2'-deoxy-3-methyl-psi-uridine (9) in 35% yield form 5.