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

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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• 10 This paper mostly reports on the tritylation reaction in the presence of DABCO in molten TBAB. Attempted microwave irradiation produces low yields and the nucleobase is lost. See: Khalafi-Nezhad A. Moktari B. Tetrahedron Lett.  2004,  45:  6737 
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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]⁺.