O⁶‐(Benzotriazol‐1‐yl)inosine Derivatives for C6 Modification of Purine Nucleosides

Abstract

A new class of reactive nucleosides, O(6)-(benzotriazol-1-yl) derivatives of inosine and 2'-deoxyinosine, have been developed via reaction of silyl-protected or unprotected inosine and 2'-deoxyinosine with 1H-benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP). Alternatively, the silyl-protected O(6)-(benzotriazol-1-yl) derivatives can be synthesized via reaction of protected inosine and 2'-deoxyinosine with triphenylphosphine/iodine/1-hydroxybenzotriazole. These new O(6)-(benzotriazol-1-yl) inosine derivatives are excellent reagents for the synthesis of other nucleoside analogues via S(N)Ar reaction with a range of nucleophiles.

Facile functionalization at the C4 position of pyrimidine nucleosides via amide group activation with (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP) and biological evaluations of the products

“…43–47 In our studies, we were the first to report O 6 -(benzotriazol-1-yl)purine nucleosides as stable, isolable, but reactive nucleoside derivatives. 35–37,39–41 In this work, we have evaluated the utility of BOP for activation of amide linkages in pyrimidine nucleosides (Figure 1), as a facile approach to modification at the C4 position.…”

Synthesis and Evaluations of “1,4‐Triazolyl Combretacoumarins” and Desmethoxy Analogs

“…Typically, 4‐azidocoumarins are prepared from 4‐hydroxycoumarins, by conversion to either the 4‐chloro or 4‐tosylate derivatives, followed by displacement with azide ion , . In our research on uncatalyzed nucleoside modification methods, we have developed facile approaches for C6 and C4 modification of purine and pyrimidine nucleosides . That chemistry involved the reaction of the oxygen atoms of the amide linkages in the nucleobases with (benzotriazol‐1yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP), a cheap and commercially available peptide‐coupling agent.…”

Two‐Step, One‐Pot Synthesis of Inosine, Guanosine, and 2′‐Deoxyguanosine O6‐Ethers via Intermediate O6‐(Benzotriazol‐1‐yl) Derivatives

“…The protocol described herein is a bridge between the actual isolation of the reactive nucleoside derivatives and in situ formation of a reactive species that undergoes further transformation. That is, as described earlier in our original publications (Bae and Lakshman 2007;Lakshman and Frank 2009) and a previous protocol (Bae et al, 2009), isolation of the reactive nucleoside derivatives S.3, its 2deoxy analog, S.7, and S.11, followed by displacement with alcohols as a separate, second step, is eminently possible. However, as described herein, isolation is not specifically necessary, and the etherification can be conducted as a two-step, one-pot operation, ensuring that S.3, S.7, or S.11 are pre-formed at the end of the first step.…”