Supported Synthesis of Adenosine Nucleotides and Derivatives on a Benzene‐Centered Tripodal Soluble Support

Abstract

The first soluble-phase synthesis of adenosine nucleotides including α,β and β,γ-methylene bisphosphonate analogues on a multi-pod support is reported. Anchoring of a 2',3'-protected purine nucleoside to the tripodal support via the nucleobase was successfully achieved using a microwave assisted Cu(I)catalyzed azide-alkyne cycloaddition. Then, phosphorylation was performed, followed by cleavage with aqueous ammonia to provide adenine derivatives, and finally deprotection. When using benzylamine instead of ammonia, a derivative with N 6benzylamine adenine as nucleobase was obtained. This methodology allows to access adenosine 5'-mono, di and triphosphates, as well as various analogues of pharmacological interest in modest to good yields.

Synthesis of Azido and Triazolyl Purine Ribonucleosides

“…Previously, the 1,2,3‐triazolyl ring was used as a leaving group only in glycosylation chemistry (Watt, Gannon, Loft, Dinev, & Williams, 2008) or in acylation with acyl benzotriazoles (Katritzky, He, & Suzuki, 2000). Recently, other applications of S N Ar reactions using 1,2,3‐triazole leaving groups have been reported (Appy, Peyrottes, & Roy, 2021).…”

Ferrocene as a potential electrochemical reporting surrogate of abasic sites in DNA

“…10 This method is particularly alluring since it is compatible with Darwinian evolution methods to identify functional nucleic acids and it is not limited in terms of size or nature of the functional groups that can be incorporated. [11][12][13][14][15][16][17][18][19][20] In the latter, modified oligonucleotides can be accessed either by primer extension (PEX) reactions or under PCR amplification conditions by substituting one or multiple canonical nucleotides with the corresponding unnatural counterparts. Natural or engineered polymerases are particularly tolerant to nucleotides bearing modifications attached at position C5 of pyrimidine or N7 of 7-deazapurine nucleotides or with simple backbone modifications but can also be coerced to incorporate nucleotides with sugar or unnatural base surrogates.…”

Ferrocene as an electrochemical reporting surrogate of abasic sites in DNA

“…10 This method is particularly alluring since it is compatible with Darwinian evolution methods to identify functional nucleic acids and it is not limited in terms of size or nature of the functional groups that can be incorporated. [11][12][13][14][15][16][17][18][19][20] In the latter, modified oligonucleotides can be accessed either by primer extension (PEX) reactions or under PCR amplification conditions by substituting one or multiple canonical nucleotides with the corresponding unnatural counterparts. Natural or engineered polymerases are particularly tolerant to nucleotides bearing modifications attached at position C5 of pyrimidine or N7 of 7-deazapurine nucleotides or with simple backbone modifications but can also be coerced to incorporate nucleotides with sugar or unnatural base surrogates.…”