0469801 - ÚOCHB 2018 RIV US eng M - Část monografie knihy
Petrová, Magdalena - Rosenberg, Ivan
Synthesis of 4′-methoxy 2′-deoxynucleoside phosphoramidites for incorporation into oligonucleotides.
Current Protocols in Nucleic Acid Chemistry. Vol. 66. Hoboken: Wiley, 2016 - (Egli, M.; Herdewijn, P.; Matsuda, A.; Sanghvi, Y.), 1.38.1-1.38.27. ISBN 978-0-471-14270-6
Grant CEP: GA ČR GA13-26526S; GA MZd NV15-31604A
Institucionální podpora: RVO:61388963
Klíčová slova: C3′-endo conformation * 4′-modified nucleosides * oligonucleotides * phosphoramidite * RNA mimics
Obor OECD: Organic chemistry
DOI: https://doi.org/10.1002/cpnc.15

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 beta-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.
Trvalý link: http://hdl.handle.net/11104/0267606