Suyeal Bae

A Novel Polymer Supported Approach to Nucleoside Modification

Polymer-supported O(6)-(benzotriazol-1-yl)inosine derivatives (Pol-I and Pol-dI) have been synthesized reasonably effectively via reaction of nucleoside phosphonium salts with polymer-linked HOBt (Pol-HOBt). In constast to solution chemistry, use of polymer-supported BOP (Pol-BOP) did not lead to efficient nucleoside loading. Presence of the nucleosides on the support could be readily detected by MAS NMR. Exposure of the polymer-supported nucleosides, Pol-I and Pol-dI, to alcohol, phenol, thiol and amine nucleophiles caused cleavage from the support leading directly to the C-6 modified nucleoside analogues. To our knowledge, these are the first examples of the application of such technology for nucleoside modification. Where possible, results of reactions with the polymer-supported nucleosides are compared to those from solution chemistry, providing insight into the differences between the two techniques. These new polymer-supported nucleosides can be conveniently utilized for diversity-oriented synthesis.

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

A new class of reactive nucleosides, O6‐(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 O6‐(benzotriazol‐1‐yl) derivatives can be synthesized via reaction of protected inosine and 2′‐deoxyinosine with triphenylphosphine/iodine/1‐hydroxybenzotriazole. These new O6‐(benzotriazol‐1‐yl) inosine derivatives are excellent reagents for the synthesis of other nucleoside analogues via SNAr reaction with a range of nucleophiles. Curr. Protoc. Nucleic Acid Chem. 36:1.22.1‐1.22.23.