357610-46-9

Basic information

• Product Name: 2-[Bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-2-[[(2R,3S,5R)-2-(2,2-dimethyl-propionyloxymethyl)-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-3-yloxy]-(2-methoxy-ethoxy)-phosphoryloxymethyl]-malonic acid diethyl ester
• CAS NO: 357610-46-9
• Molecular Weight: 968.989
• Mol File: 357610-46-9.mol
• Article Data: 1

Chemical Properties

• CAS DataBase Reference: 2-[Bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-2-[[(2R,3S,5R)-2-(2,2-dimethyl-propionyloxymethyl)-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-3-yloxy]-(2-methoxy-ethoxy)-phosphoryloxymethyl]-malonic acid diethyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: 2-[Bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-2-[[(2R,3S,5R)-2-(2,2-dimethyl-propionyloxymethyl)-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-3-yloxy]-(2-methoxy-ethoxy)-phosphoryloxymethyl]-malonic acid diethyl ester(357610-46-9)
• EPA Substance Registry System: 2-[Bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-2-[[(2R,3S,5R)-2-(2,2-dimethyl-propionyloxymethyl)-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-3-yloxy]-(2-methoxy-ethoxy)-phosphoryloxymethyl]-malonic acid diethyl ester(357610-46-9)

Safety Data

• Hazardous Substances Data: 357610-46-9(Hazardous Substances Data)

Upstream product

• 40615-36-9 4,4'-dimethoxytrityl chloride 
• 20605-01-0 diethyl bis(hydroxymethyl)malonate 
• 109-86-4 2-methoxy-ethanol 
• 40733-25-3 2'-deoxy-5'-O-pivaloylthymidine 
• 171285-26-0 diethyl 2-hydroxymethyl-2-(4,4'-dimethoxytrityloxymethyl)malonate 

Relevant articles and documents

Hydrolytic stability of nucleoside phosphotriesters derived from bis(hydroxymethyl)-1,3-dicarbonyl compounds and their congeners: Towards a novel pro-drug strategy for antisense oligonucleotides

Four different nucleoside phosphodiester protecting groups derived from bis(hydroxymethyl)-1,3-dicarbonyl compounds and their congeners have been prepared and introduced to 5′-O-pivaloylthymidine 3′-(2-methoxyethyl)-phosphate and its monothioate analogs. Nucleoside phosphotriesters having either 2,2-bis(ethoxycarbonyl)-3-(4,4′-dimethoxytrityloxy)propyl (1a), 2-cyano-2-methoxycarbonyl-3-(4,4′-dimethoxytrityloxy)propyl (1b), 2,2-bis(cyano)-3-(4,4′-dimethoxytrityloxy)propyl (1c) or 2-acetyl-2-benzoyl-3-(4,4′-dimethoxytrityloxy)propyl (1d) protecting group have been prepared. Additionally were synthesized the O- and S-esterified phosphoromonothioate analogs of 1b. After removal of the dimethoxytrityl group under acidic conditions, each of the detritylated protecting groups is readily cleaved from the phosphate/thiophosphate moiety by a reaction suggested to involve a base-catalyzed retro-aldol condensation and following elimination of the phosphodiester from the formed carbanion intermediate. The kinetics of the hydroxide ion-catalyzed cleavage have been studied by HPLC over a pH range 2-7. The half-lives of the cleavage at pH 7 and 25 °C vary from 0.3 s (for1c) to 5500 s (for 1a). The results confirm that these protecting groups have promising chemical properties for use in the development of antisense oligonucleotide pro-drug strategies.