Nucleosides, nucleotides and nucleic acids p. 307 - 314 (2006)
Update date:2022-08-29
Topics:
Kore, Anilkumar
Parmar, Gaurang
Reddy, Srinu
An improved strategy for the selective synthesis of 2′- O -methyl and 3′- O -methyl guanosine from 2-aminoadenosine is reported by using the catalyst stannous chloride. The regioselectivity of the 2′ and 3′- O -alkylation was achieved by optimizing the addition, timing, and concentration of the catalysts and diazomethane during the methylation reaction. An efficient and selective alkylation at 2′-OH of 2-aminoadenosine was achieved by mixing a stoichiometric amount of stannous chloride at room temperature in DMF. The reaction mixture was stirred at 50°C for 1 min and immediately followed by addition of diazomethane. The resulting 2′- O -methyl 2-aminoadenosine was treated with the enzyme adenosine deaminase, which resulted in an efficient conversion to the desired 2′- O -methylguanosine (98% yield). The product was isolated by crystallization. In contrast, the methylation at 3′-OH of 2-aminoadenosine was achieved by mixing a stoichiometric amount of stannous chloride in DMF and stirring at 50°C for 15 min, followed by addition of diazomethane. The resulting mixture containing 3′- O -methyl-2- aminoadenosine in 90% yield and 2′- O -methyl-2-aminoadenosine in 10% yield was treated with the enzyme adenosine deaminase, which preferentially deaminated only 3′- O -methyl-2-aminoadenosine, resulting in the production of 3′- O -methylguanosine in 88% yield. Due to the extremely low solubility 3′- O -methylguanosine, the compound precipitated and was isolated by centrifugation. This synthetic route obviates the chromatographic purification. Selective monomethylation is achieved by using the unprotected ribonucleoside. As a result, the method described herein represents a significant improvement over the current synthetic approach by providing superior product yield and economy, a much more facile purification of 2′,3′- O -methylated isomers, and eliminating the need for protected ribonucleosides reagents. Copyright Taylor & Francis Group, LLC.
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