This review focuses on new trends in nucleoside biotechnology, which have emerged during the
last decade. Continuously growing interest in the study of this class of compounds is fueled by
a number of factors: ( i ) a growing need for large–scale production
of natural 2 ′ –deoxy– β –D–ribonucleosides as well as their
analogs with modifications in the carbohydrate and base fragments, which can then be used for
the synthesis and study of oligonucleotides, including short–interfering RNA (siRNA),
microRNA (miRNA), etc.; ( ii ) a necessity for the development of efficient
practical technologies for the production of biologically important analogs of natural
nucleosides, including a number of anticancer and antiviral drugs; ( iii ) a
need for further study of known and novel enzymatic transformations and their use as tools for
the efficient synthesis of new nucloside analogs and derivates with biomedical potential. This
article will review all of these aspects and also include a brief retrospect of this field of
research.
Trinucleotide phosphoramidites that correspond to the codons of all 20 amino acids were synthesized in high yield in 5g scale. Precursors of those amidites--trinucleotide phosphotriesters--have been prepared using the phosphotriester approach without protection of the 3'-hydroxyl function. The structures of trinucleotide phosphotriesters and intermediates were confirmed by 1H- and 31P-NMR spectra, mass-spectra and by analysis of SPDE-hydrolysates of deprotected preparations. Purity of the target products has been confirmed by test reactions. The synthons have been used for automated synthesis of oligonucleotides and corresponding libraries by a phosphite-triester approach. A 54mer, containing 12 randomized internal bases, and a 72mer with 24 internal randomized bases have been synthesized.
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