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Synlett 2024; 35(06): 684-690
DOI: 10.1055/a-2174-2554
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Special Issue to Celebrate the Centenary Year of Prof. Har Gobind Khorana

Serendipitous Synthesis of 5-Hydroxyuridine from 2′,3′-O-Isopropylidene N4-Acetylcytidine by Hypervalent Iodine(III)-Mediated Reaction

Mary Anne Maverick
,
Mathieu Noël
,
Jean-Jacques Vasseur 
,
Carine Baraguey∗
,
Françoise Debart  ∗
,
Michael Smietana  ∗
The GAVO consortium is gratefully acknowledged for financial support.
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Abstract

Whereas BAIB-TEMPO oxidation of 2′,3′-O-TBDMS-N4-acetylcytidine results in the expected 5′-carboxylic acid nucleoside, its 2′,3′-O-isopropylidene analogue reacts in a radically different way. We have demonstrated here that hypervalent iodine(III) in water triggers an unprecedented oxidative cyclization leading to a mixture of C5-substituted O6,5′-cyclo-5,6-dihydrouridines. This mixture of cyclouridines can be opened under basic conditions and, after deprotection, yields 5-hydroxyuridine, an important post-transcriptional modification of uridine at the wobble position (U34) of bacterial tRNA. NMR experimental values and calculations were performed to provide further insight on the specific reactivity of 2′,3′-O-isopropylidene N4-acetylcytidine.

Key words

hypervalent iodine - nucleosides - cyclouridine - oxidative cyclization - 5-hydroxyuridine

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-2174-2554.
  • Supporting Information


Publication History

Received: 15 July 2023

Accepted after revision: 12 September 2023

Accepted Manuscript online:
12 September 2023

Article published online:
18 October 2023

© 2023. Thieme. All rights reserved

Georg Thieme Verlag KG
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  • References and Notes

  • 4 Eaton MA. W, Hutchinson DW. Biochim. Biophys. Acta 1973; 319: 281
    CrossrefPubMedSearch in Google Scholar
  • 5 Mieczkowski A, Roy V, Agrofoglio LA. Chem. Rev. 2010; 110: 1828
    CrossrefPubMedSearch in Google Scholar
  • 6 Gissot A, Massip S, Barthelemy P. ACS Omega 2020; 5: 24746
    CrossrefPubMedSearch in Google Scholar
  • 7 Kozak W, Demkowicz S, Dasko M, Rachon J, Rak J. Russ. Chem. Rev. 2020; 89: 281
    CrossrefPubMedSearch in Google Scholar
  • 8 Nabel CS, Manning SA, Kohli RM. ACS Chem. Biol. 2012; 7: 20
    CrossrefPubMedSearch in Google Scholar
  • 9 Kameyama K, Sako M, Hirota K, Maki Y. J. Chem. Soc., Chem. Commun. 1984; 1658
    Crossref
  • 10 Maverick MA, Gaillard M, Vasseur JJ, Debart F, Smietana M. Eur. J. Org. Chem. 2022; e202101061
    Crossref
  • 11 Clavé G, Dursun E, Vasseur J.-J, Smietana M. Org. Lett. 2020; 22: 1914
    CrossrefPubMedSearch in Google Scholar
  • 12 Epp JB, Widlanski TS. J. Org. Chem. 1999; 64: 293
    CrossrefPubMedSearch in Google Scholar
  • 13 Dudycz L, Stolarski R, Pless R, Shugar D. Z. Naturforsch., C: J. Biosci. 1979; 34: 359
    CrossrefPubMedSearch in Google Scholar
  • 14 General Procedure for the Synthesis of 3 and 5: 2′,3′-O-Isopropylidene N4-acetylcytidine (200 mg, 0.615 mmol) and bis(acetoxy)iodobenzene (396 mg, 1.23 mmol) were dissolved in a mixture of CH3CN/water (5:5 v/v, 1.23 mL) and the mixture was stirred for 3 h at room temperature. The solvent was evaporated under vacuum and the crude material was purified by chromatography on silica gel (EtOAc/cyclohexane, 50 to 80%) to afford compound 3 (149 mg, 71%) and compound 5 (22 mg, 11%) as white powders.Compound 3: 1H NMR (CDCl3, 298 K, 500 MHz): δ = 8.03 (bs, 1 H), 6.28 (s, 1 H), 5.50 (d, 1 H), 5.00 (d, 1 H), 4.73 (s, 2 H), 4.51 (d, 1 H), 4.14 (d, 1 H), 3.70 (dd, 1 H), 2.22 (s, 3 H), 1.52 (s, 3 H), 1.32 (s, 3 H). 13C NMR (CDCl3, 298 K, 125 MHz): δ = 169.5, 164.1, 148.6, 113.0, 92.4, 87.7, 87.2, 86.6, 82.6, 75.8, 70.1, 26.4, 24.8, 20.7. HRMS (ESI+): m/z [M + H]+ calcd. for C14H19N2O8: 343.1141; found: 343.1136.Compound 5: 1H NMR (CDCl3, 298 K, 500 MHz): δ = 8.06 (bs, 1 H), 6.29 (s, 1 H), 4.85 (d, 1 H), 4.75 (d, 1 H), 4.71 (d, 1 H), 4.53 (d, 1 H), 4.28 (d, 1 H), 4.24 (d, 1 H), 3.80 (dd, 1 H), 1.52 (s, 3 h), 1.33 (s, 3 H). 13C NMR (CDCl3, 298 K, 150 MHz): δ = 169.0, 148.7, 113.0, 92.3, 89.8, 87.7, 86.5, 82.7, 76.2, 70.5, 26.4, 24.8. HRMS (ESI+): m/z [M + H]+ calcd. for C12H17N2O7: 301.1036; found: 301.1030.
  • 15 Rupanawar BD, Mane KD, Suryavanshi G. New J. Chem. 2022; 46: 16832
    CrossrefPubMedSearch in Google Scholar
  • 17 Soni R, Sihag M, Rani N, Kinger M, Aneja DK. Asian J. Org. Chem. 2022; e202200125
    Crossref
  • 18 Lakshman MK, Zajc B. ARKIVOC 2018; (ii): 252
    CrossrefPubMedSearch in Google Scholar
  • 20 Synthesis of 5-OHU: Compound 6 (92 mg, 0.305 mmol) was treated with a formic acid/water solution (9 mL, 1:1, v/v) for 24 h at room temperature. The solvent was evaporated under vacuum and the residue was co-evaporated with EtOH. The crude material was purified on C18-reverse-phase flash chromatography using an isocratic 20 mM TEAAc buffer (pH 7). Pure fractions containing the desired compound were pooled, evaporated and lyophilized from water to afford 5-OHU (71.4 mg, 0.274 mmol, 90%).
  • 21 1H NMR (D2O, 298 K, 500 MHz): δ = 7.37 (s, 1 H), 5.83 (d, 1 H), 4.23 (t, 1 H), 4.13 (t, 1 H), 4.02 (m, 1 H), 3.81 (dd, 1 H), 3.70 (dd, 1 H). 13C NMR (D2O, 298 K, 125 MHz): δ = 162.2, 150.4, 132.6, 121.3, 88.6, 84.2, 73.3, 69.5, 60.7. HRMS (ESI–): m/z [M–H]– calcd. for C9H11N2O7: 259.0572; found: 259.0581.
  • 22 Altona C, Sundaralingam M. J. Am. Chem. Soc. 1973; 95: 2333
    CrossrefPubMedSearch in Google Scholar
  • 23 Katti SK, Seshadri TP, Viswamitra MA. Acta Crystallogr., Sect. B: Struct. Sci. 1981; 37: 407
    CrossrefSearch in Google Scholar
  • 25 van de Ven FJ. M, Hilbers CW. Eur. J. Biochem. 1988; 178: 1
    CrossrefPubMedSearch in Google Scholar
  • 26 Haasnoot CA. G, de Leeuw FA. A. M, de Leeuw HP. M, Altona C. Org. Magn. Reson. 1981; 15: 43
    CrossrefSearch in Google Scholar
  • 27 Haasnoot CA. G, Deleeuw F, Altona C. Tetrahedron 1980; 36: 2783
    CrossrefSearch in Google Scholar