title: Synthesis of 4'-Methoxy 2'-Deoxynucleoside Phosphoramidites for Incorporation into Oligonucleotides.
abstract: This unit contains detailed synthetic protocols for the preparation of 4'-methoxy 2'-deoxynucleoside phosphoramidite monomers for A, G, C, T, and U. First, 3'-silyl-protected 2'-deoxynucleosides (dNs) are converted in two steps to 4',5'-enol acetates as the key starting compounds. Next, 4'-methoxy dNs are prepared by a one-pot procedure comprising N-iodosuccinimide-promoted methoxylation, hydrolysis, and reduction of the formed intermediates. Finally, 3'-phosphoramidites of 4'-methoxy dNs are obtained by a routine three-step procedure. Title phosphoramidite monomers are suitable for the synthesis of oligonucleotides on solid phase according to conventional amidite chemistry. 4'-Methoxy substitution represents a simple modification of the sugar part of dNs, where β-D-erythro epimers preferentially adopt N-type (C3'-endo, RNA-like) conformation. Moreover, it imparts superior chemical stability, nuclease resistance, and excellent hybridization properties to modified 4'-methoxyoligodeoxynucleotides. The strong tendency toward RNA-selective hybridization suggests its potential utilization in antisense and/or RNAi technologies. © 2016 by John Wiley & Sons, Inc.
authors: Department of Bioorganic and Medicinal Chemistry, The Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague, Czech Republic.
authors: Magdalena
authors: M
authors: Petrová
authors: Department of Bioorganic and Medicinal Chemistry, The Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague, Czech Republic.
authors: Ivan
authors: I
authors: Rosenberg
mesh_terms: D060326:Chemistry Techniques, Synthetic; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D009841:Oligonucleotides; D009943:Organophosphorus Compounds; C434331:phosphoramidite
keywords: 4′-modified nucleosides; C3′-endo conformation; RNA mimics; oligonucleotides; phosphoramidite