Effective isomerization of 3',5'-O-(tetraisopropyldisiloxane-1,3- diyl)nucleosides in the presence of trimethylsilyl trifluoromethanesulfonate
Irina V. Kulikova, Daria A. Muradova, and Sergey N. Mikhailov*
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov str. 32, Moscow, 119991 Russia
E-mail: smikh@eimb.ru
Dedicated to Prof. Harri Lönnberg on his 60th birthday
Abstract
Trimethylsilyl trifluoromethanesulfonate catalyze effective isomerization of 3',5'-O- (tetraisopropyldisiloxane-1,3-diyl)nucleosides (1) in 1,2-dicloroethane at 0°C into 2',3'-O- (tetraisopropyldisiloxane-1,3-diyl)-derivatives (2), which can be obtained in 55-90% yields. On the other hand nucleosides 1 were found to be stable in the presence of tin tetrachloride. Only in the case of uridine derivative 1a a substantial amount of isomerization product 2a was formed.
Keywords: nucleoside protection, isomerization, 3',5'-O-(tetraisopropyldisiloxane-1,3- diyl)nucleosides, trimethylsilyl trifluoromethanesulfonate
Introduction
Tetraisopropyldisiloxane-1,3-diyl (TIPDS) group developed by Markiewicz1,2 is widely used for simultaneous protection of 3',5'-hydroxyl groups in ribonucleosides and subsequent manipulation with 2'-OH group of ribonucleosides: deoxygenation,3,4 oxidation,5 alkylation,6-10 glycosylation,11-16 protection,17-21 preparation of 2'-amino-2'-deoxynuclesides,22,23 and so on. This group may be considered as one of the most popular and useful protecting group in the field of nucleoside chemistry. It is believed that the reaction of 1,3-dichloro-tetraisopropyldisiloxane with ribonucleoside starts with silylation of primary 5'-hydroxyl followed by the formation of an 8-membered ring. It was also shown that the reaction with 5'-O-protected ribonucleosides resulted in the formation of 2',3'-O-derivatives with 7 membered ring.1,24,25 It should be also mentioned that simultaneous protection of both 3'- and 5'-hydroxyls can be carried out with N- unprotected ribonucleosides and with base-protected N-acyl derivatives. TIPDS group is removed with fluoride ion, usually with Bu4NF.3H2O in tetrahydrofuran.26
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