2140-71-8Relevant articles and documents
Noncanonical RNA Nucleosides as Molecular Fossils of an Early Earth—Generation by Prebiotic Methylations and Carbamoylations
Schneider, Christina,Becker, Sidney,Okamura, Hidenori,Crisp, Antony,Amatov, Tynchtyk,Stadlmeier, Michael,Carell, Thomas
supporting information, p. 5943 - 5946 (2018/04/30)
The RNA-world hypothesis assumes that life on Earth started with small RNA molecules that catalyzed their own formation. Vital to this hypothesis is the need for prebiotic routes towards RNA. Contemporary RNA, however, is not only constructed from the four canonical nucleobases (A, C, G, and U), it also contains many chemically modified (noncanonical) bases. A still open question is whether these noncanonical bases were formed in parallel to the canonical bases (chemical origin) or later, when life demanded higher functional diversity (biological origin). Here we show that isocyanates in combination with sodium nitrite establish methylating and carbamoylating reactivity compatible with early Earth conditions. These reactions lead to the formation of methylated and amino acid modified nucleosides that are still extant. Our data provide a plausible scenario for the chemical origin of certain noncanonical bases, which suggests that they are fossils of an early Earth.
An efficient process for synthesis of 2′-O-methyl and 3′-O-methyl guanosine from 2-aminoadenosine using diazomethane and the catalyst stannous chloride
Kore, Anilkumar,Parmar, Gaurang,Reddy, Srinu
, p. 307 - 314 (2007/10/03)
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.
Novel synthesis of 2′-O-methylguanosine
Chow, Suetying,Wen, Ke,Sanghvi, Yogesh S.,Theodorakis, Emmanuel A.
, p. 1631 - 1634 (2007/10/03)
An efficient and chemoselective synthesis of 2′-O-methylguanosine (6) has been accomplished in high yield without protection of the guanine base. The salient feature of the synthesis of 6 lies in the application of methylene-bis-(diisopropylsilyl chloride), (MDPSCl2, 2) as a new 3′,5′-O-protecting group for nucleosides. Use of CH3Cl as a weak electrophile and NaHMDS as a mild base was crucial to the success of the 2′-O-methylation of 3′,5′-O-protected guanosine.
