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Synlett 2006(20): 3474-3478  
DOI: 10.1055/s-2006-958430
LETTER
© Georg Thieme Verlag Stuttgart · New York

Pyridine-Free and Solvent-Free Acetylation of Nucleosides Promoted by Molecular Sieves

Marcus Mandolesi Sá*, Lidiane Meier
Departamento de Química, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil
Fax: +55(48)33316850; e-Mail: msa@qmc.ufsc.br;
Further Information

Publication History

Received 1 September 2006
Publication Date:
08 December 2006 (online)

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Abstract

A practical method for the acetylation of purine and ­pyrimidine nucleosides employing a combination of acetic an­hydride and potassium-exchanged molecular sieves is described. Besides the high yields obtained for the acylated nucleosides, the procedure is simple, inexpensive and environmentally benign, avoiding the use of pyridine or co-solvents as additives.

Key words

green chemistry - acylation - heterogeneous catalysis - molecular sieves - nucleosides

11

Preparation of Potassium-Exchanged Molecular Sieves.
A suspension of the appropriate molecular sieves (1.0 g) and 1 M KCl (10 mL) was stirred at r.t. for 15-18 h, followed by vacuum filtration and air-drying, obtaining a clear amorphous solid that can be stored for months without any special precautions.
General Procedure for the Synthesis of Acetylated Nucleosides 1-10.
Nucleoside (1.0 mmol), catalyst (0.6 g) and Ac2O (8-10 mmol) were stirred at 90-100 °C for the time indicated in Table [2] . The final mixture was cooled to r.t., filtered, the catalyst was rinsed with CH2Cl2, and the filtrate was concentrated under reduced pressure. The resulting residue was diluted in EtOAc and washed with sat. NaHCO3 and H2O. Then the aqueous phases were back-extracted with CH2Cl2 and the combined organic extracts were dried over Na2SO4, filtered and concentrated to give a solid residue that was purified by recrystallization with CH2Cl2.
Selected Data.
2′,3′,5′-O-Triacetylxanthosine (4): white solid; mp 135-137 °C. IR (KBr): νmax = 3475, 3193, 1749, 1700, 1232 cm-1. 1H NMR (400 MHz, DMSO-d 6): δ = 2.04 (s, 3 H, CH3), 2.10 (s, 6 H, CH3), 4.22-4.38 (m, 3 H, H-4′ and H-5′), 5.39 (m, 1 H, H-3′), 5.66 (t, J = 5.5 Hz, 1 H, H-2′), 6.04 (d, J = 5.5 Hz, 1 H, H-1′), 7.86 (s, 1 H, H-8), 10.33 (s, 1 H, D2O exchange). 13C NMR (100 MHz, DMSO-d 6): δ = 25.64 (CH3), 25.78 (CH3), 25.96 (CH3), 68.40 (CH2), 75.16 (CH), 77.69 (CH), 84.80 (CH), 89.98 (CH), 120.72 (C), 139.40 (CH), 150.20 (C), 158.83 (C), 163.88 (C), 174.74 (C=O), 174.89 (C=O), 175.54 (C=O). Anal. Calcd for C16H18N4O9·2H2O (%): C, 43.05; H, 4.97; N, 12.55. Found: C, 43.28; H, 4.57; N, 12.74.
2′,3′-O-Isopropylidene-2-N-5′-O-diacetylguanosine (9b): white solid; mp 124-125 °C. IR (KBr): νmax = 3454, 3202, 3178, 1738, 1708, 1683, 1250 cm-1. 1H NMR (400 MHz, DMSO-d 6): δ = 1.32 (s, 3 H, CH3), 1.52 (s, 3 H, CH3), 1.97 (s, 3 H, CH3), 2.20 (s, 3 H, CH3), 4.08 (dd, J = 7.0, 12.0 Hz, 1 H, H-5′), 4.19 (dd, J = 4.5, 12.0 Hz, 1 H, H-5′), 4.30 (m, 1 H, H-4′), 5.18 (dd, J = 3.5, 6.5 Hz, 1 H, H-3′), 5.30 (dd, J = 2.0, 6.5 Hz, 1 H, H-2′), 6.11 (d, J = 2.0 Hz, 1 H, H-1′), 8.16 (s, 1 H, H-8), 11.54 (s, 1 H, D2O exchange), 12.07 (s, 1 H, D2O exchange). 13C NMR (100 MHz, DMSO-d 6): δ = 21.19 (CH3), 24.61 (CH3), 26.04 (CH3), 27.69 (CH3), 64.54 (CH2), 81.47 (CH), 84.29 (CH), 84.92 (CH), 89.24 (CH), 114.15 (C), 121.33 (C), 139.19 (CH), 148.56 (C), 148.64 (C), 155.46 (C), 170.76 (C=O), 174.23 (C=O). Anal. Calcd for C17H21N5O7·H2O (%): C, 48.00; H, 5.45; N, 16.46. Found: C, 47.92; H, 5.80; N, 16.41.
General Procedure for the Microwave-Assisted Synthesis of Acetylated Nucleosides.
Microwave reactions were performed in 10 mL sealed tubes in a commercially available monomode reactor (CEM Discover) with IR temperature monitoring and non-invasive pressure transducer. In a typical procedure, nucleoside (1.0 mmol), Ac2O (8-10 mmol) and the catalyst (0.6 g) were placed in a 10 mL glass tube. The vessel was then sealed with a septum, placed into the microwave cavity and irradiated with stirring under the conditions presented in Table [3] . After allowing the mixture to cool to r.t., the reaction vessel was opened and the contents were treated as above to give pure acetylated products after recrystallization.