Synthesis of 2'-deoxynucleosides of purine derivatives using lewis catalyst, CsI.

Abstract

The synthesis of 2``-deoxynucleosides of purine derivatives using catalyst, cesium iodide (CsI) was studied. In order to prepare the 2``-deoxynucleosides, purine bases were converted into their trimethylsilyl derivatives by treatment with hexamethyldisilazane (HMDS) in the presence of ammonium sulfate as catalyst, followed by distillation of HMDS. This trimethylsilyl derivatives were reacted with 2-deoxy-3,5-di-O-p-toluoyl-erythro-pentosyl chloride($\alpha$-chlorosugar) in anhydrous acetonitrile in the presence of cesium iodide as catalyst to give the corresponding protected 2``-deoxy nucleosides of purine derivatives. Deacylation of the protected 2``-deoxynucleosides in saturated methanolic ammonia at 0 - $5\,^\circ\!C$ afforded the anomeric mixture of 2``-deoxynucleosides of purine derivatives. The anomeric mixture was seperated by eluting appropriate solvent systems on silica gel preparative TLC. The results commonly showed high yield of purine bases, but low $\beta/\alpha$ ratio. For the synthesis of 5-bromo-2,3-trideoxy-D-ribofuranosyl acetate, (S)(+)-$\gamma$-tosylmethyl-$\gamma$-butyrolactone was synthesized by the known method. Bromination of this compound gave (S)-$\gamma$-brome-$\gamma$-butyrolactone. Reduction of (S)-$\gamma$-butyrolactone using diisobutylaluminiumhydride (DIBAL-H) followed by acetylation gave 5-bromo-2,3,5-trideoxy-D-ribofuranosyl acetate.