Synthesis of 2′-Deoxy-2′-C-α-methylpurine Nucleosides

Nan-Sheng Li; Joseph A. Piccirilli

doi:10.1055/s-2005-872204

PAPER

Synthesis of 2′-Deoxy-2′-C-α-methylpurine Nucleosides

Nan-Sheng Li*, Joseph A. Piccirilli*
Howard Hughes Medical Institute, Department of Biochemistry & Molecular Biology and Department of Chemistry, University of Chicago, 5841 S. Maryland Ave., MC 1028, Chicago, IL 60637, USA
Fax: +1(773)7020271; e-Mail: nli@uchicago.edu; e-Mail: jpicciri@uchicago.edu;

Abstract

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Abstract

2′-Deoxy-2′-C-α-methylribonucleosides provide valuable biochemical probes with which to study RNA structure and function. Using methyl 2-acetoxymethyl-3,5-di-O-(tert-butyldimethylsilyl)-d-ribofuranoside (1) as a glycosylating agent, we achieved in four steps an improved synthesis of 2′-deoxy-2′-C-α-methyladenosine (8) and the first synthesis of 2′-deoxy-C-α-methylguanosine (9) in 25% and 17% overall yield, respectively.

Key words

nucleosides - deoxygenation - glycosylation - deoxymethyladenosine - deoxymethylguanosine

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References

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<A NAME="RM02705SS-12">12</A> The ¹³C NMR data of the adenine ring are assigned as follows: For 2a (CDCl₃): δ = 152.6 (C-6), 151.7 (C-2), 149.3 (C-4), 142.8 (C-8), 122.2 (C-5) and 2b (CDCl₃): δ = 152.7 (C-6), 151.8 (C-2), 149.5 (C-4), 141.6 (C-8), 123.2 (C-5); cf. experimental section. For 7-methyladenine (DMSO-d ₆): δ = 159.82 (C-4), 152.31 (C-2), 151.91 (C-6), 145.94 (C-8), 111.77 (C-5) and 9-methyladenine (DMSO-d ₆): δ = 155.98 (C-6), 152.50 (C-2), 149.94 (C-4), 141.47 (C-8), 118.72 (C-5); see: Chenon M.-T. Pugmire RJ. Grant DM. Panzica RP. Townsend LB. J. Am. Chem. Soc. 1975, 97: 4627

<A NAME="RM02705SS-13">13</A> The ¹³C NMR data of the guanine ring are assigned as follows: For 3a (CDCl₃): δ = 155.9 (C-6), 148.2 (C-4), 147.4 (C-2), 138.9 (C-8), 120.4 (C-5), 3b (CDCl₃): δ = 156.0 (C-6), 148.4 (C-4), 147.4 (C-2), 137.0 (C-8), 120.8 (C-5) and 3c (CDCl₃): δ = 156.8 (C-6), 152.8 (C-4), 148.2 (C-2), 141.6 (C-8), 111.4 (C-5); cf. experimental section. For N ²-acetyl-2′,3′,5′-tri-O-acetyl-9-guanosine (DMSO-d ₆): δ = 154.68 (C-6), 148.58 (C-4), 148.22 (C-2), 137.79 (C-8), 120.38 (C-5) and N ²-acetyl-2′,3′,5′-tri-O-acetyl-7-guanosine (DMSO-d ₆): δ = 158.37 (C-6), 152.17 (C-4), 147.51 (C-2), 144.12 (C-8), 110.56 (C-5); see: Boryski J. J. Chem. Soc., Perkin Trans. 2 1997, 649