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Synlett 2007(11): 1733-1735  
DOI: 10.1055/s-2007-982532
LETTER
© Georg Thieme Verlag Stuttgart · New York

Microwave-Assisted Selective 5′-O-Trityl Protection of Inosine Derivatives

Elena Casanovaa,b, María-Jesús Pérez-Péreza, C. Oliver Kappe*b
a Instituto de Química Médica (C.S.I.C.), Juan de la Cierva, 3, 28006 Madrid, Spain
b Christian Doppler Laboratory for Microwave Chemistry (CDLMC) and Institute of Chemistry, Karl-Franzens-University Graz, Heinrichstrasse 28, 8010 Graz, Austria
Fax: +43(316)3809840; e-Mail: oliver.kappe@uni-graz.at;
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Publication History

Received 12 March 2007
Publication Date:
25 June 2007 (online)

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Abstract

The efficient microwave-assisted synthesis of 5′-O-trityl inosine derivatives is described. The reported protocol allows the protection of inosine derivatives in significantly higher yields and shorter reaction times than the standard thermal conditions. This procedure is particularly suitable for modified inosines where the 5′-OH is sterically hindered (i.e. 8-bromoinosine).

Key words

protecting groups - microwave synthesis - nucleosides - tritylether - medicinal chemistry

    References and Notes

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13

Spectroscopic data for N 1-benzylinosine (4): 1H NMR (360 MHz, DMSO-d 6): δ = 3.60 (m, 2 H, H-5′), 3.93 (m, 1 H, H-4′), 4.11 (m, 1 H, H-3′), 4.48 (m, 1 H, H-2′), 5.05 (t, J = 5.7 Hz, 1 H, OH), 5.21-5.23 (m, 3 H, CH2, OH), 5.49 (m, 1 H, OH), 5.85 (d, J = 5.8 Hz, 1 H, H-1′), 7.24-7.36 (m, 5 H, Ph), 8.36, 8.62 (s, 2 H, H-2, H-8). MS (ES, positive mode): m/z = 358 [M + 1]+.

16

Spectroscopic data for 8-bromo-5′-O-tritylinosine (8): white solid, mp 175-178 °C (MeOH). 1H NMR (300 MHz, DMSO-d 6): δ = 3.16 (m, 2 H, H-5′), 4.05 (m, 1 H, H-4′), 4.42 (m, 1 H, H-3′), 5.06 (m, 1 H, H-2′), 5.22 (d, J = 4.8 Hz, 1 H, OH), 5.56 (d, J = 5.7 Hz, 1 H, OH), 5.83 (d, J = 4.2 Hz, 1 H, H-1′), 7.19-7.30 (m, 15 H, Ph), 7.88 (s, 0.66 H, H-2), 7.93 (s, 0.33 H, H-2), 12.56 (br s, 1 H, NH). MS (ES, positive mode): m/z = 589 [M + 1]+.