Chemoenzymatic Synthesis of 3′-O-Acetal-Protected 2′-Deoxynucleosides as Building Blocks for Nucleic Acid Chemistry†

We have developed a simple and convenient synthetic strategy for the preparation of tetrahydropyranyl, 4-methoxy-tetrahydropyranyl, and tetrahydrofuranyl ethers of 2'-deoxynucleosides, which are useful building blocks for nucleic acid chemistry. Enzymatic benzoylation provides an efficient alternative for protecting the 5'-hydroxy group of the parent nucleosides in a regioselective manner. Subsequently, tetra-hydropyranylation and tetrahydrofuranylation of the 2'-deoxynucleosides at the 3'-hydroxy group were accomplished with p-toluensulfonic acid, MgBr 2 , or camphorsulfonic acid as catalysts. Deprotection of the 5'-O-benzoyl group furnished 3'-O-acetal-protected 2'-deoxynucleosides. The three-step process is expected to enable the large-scale synthesis of protected nucleosides.