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

• Published in: European Journal of Organic Chemistry 2010-03, Vol.2010 (9), p.1736-1744
• Main Authors: Rodríguez-Pérez, Tatiana, Fernández, Susana, Martínez-Montero, Saúl, González-García, Tania, Sanghvi, Yogesh S., Gotor, Vicente, Ferrero, Miguel
• Format: Article
• Language: English
• Subjects: Acylation; Bioconversions. Hemisynthesis; Biological and medical sciences; Biotechnology; Carbohydrates. Nucleosides and nucleotides; Catalysis; Catalysts: preparations and properties; Chemistry; Enzymes; Exact sciences and technology; Fundamental and applied biological sciences. Psychology; General and physical chemistry; Green chemistry; Methods. Procedures. Technologies; Nucleosides; Nucleosides, nucleotides and oligonucleotides; Organic chemistry; Preparations and properties; Protecting groups; Theory of reactions, general kinetics. Catalysis. Nomenclature, chemical documentation, computer chemistry
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.200901428

We have developed a simple and convenient synthetic strategy for the preparation of tetrahydropyranyl, 4‐methoxytetrahydropyranyl, 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, tetrahydropyranylation and tetrahydrofuranylation of the 2′‐deoxynucleosides at the 3′‐hydroxy group were accomplished with p‐toluensulfonic acid, MgBr2, 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. A simple and convenient chemoenzymatic strategy for the preparation of tetrahydropyranyl, 4‐methoxytetrahydropyranyl, and tetrahydrofuranyl ethers of 2′‐deoxynucleosides, which are useful building blocks for nucleic acid chemistry, has been developed. The three‐step process is expected to enable the large‐scale synthesis of protected nucleosides.