Process Research on the Preparation of DMT Protected 2′-O-Methoxyethylguanosine for Oligonucleotide Synthesis in Therapeutic Applications

Abstract

An optimized process to synthesize DMT protected 2 ′-O-methoxyethylguanosine is described. A key step involves the enzymatic deamination of a mixture of alkylated products to selectively afford the desired material without resorting to chromatography for purification. This approach was scaled up to kilogram quantities for use in oligonucleotide therapeutics.

Keywords:

• Oligonucleotides
• antisense
• 2-aminoadenosine
• diaminopurine riboside
• modified nucleoside
• 2′-O-methoxyethylguanosine
• adenosine deaminase