Synlett 2021; 32(11): 1135-1140
DOI: 10.1055/a-1509-9275
letter

A Single-Step Asymmetric Phosphodiester Synthesis from Alcohols with Phosphoenolpyruvate Phosphodiester

Kohei Fujiyoshi
,
Shigehiro A. Kawashima
,
,
Motomu Kanai
This work was supported from the Japan Society for the Promotion of Science (JSPS KAKENHI Grant Numbers JP17K15420 and JP20H00489, K.Y. and M.K.), and SUNBOR Grant (K.Y.).


Abstract

Phosphodiesters are important structural motifs observed in a diverse field of molecular science. It is, thus, important to develop a simple and robust way to synthesize them from corresponding alcohols. Here we report a single-step asymmetric phosphodiester synthesis from alcohols with phosphoenolpyruvate phosphodiesters as phosphoryl donors. This transformation allows for the use of various functionalized alcohols as substrates and would be useful for diverse fields including biology and medicine.

Supporting Information



Publication History

Received: 05 May 2021

Accepted after revision: 17 May 2021

Accepted Manuscript online:
17 May 2021

Article published online:
08 June 2021

© 2021. Thieme. All rights reserved

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  • References and Notes

  • 1 Hunter T. Philos. Trans. R. Soc., B 2012; 367: 2513
  • 2 Kirby AJ, Nome F. Acc. Chem. Res. 2015; 48: 1806
  • 3 Sinden RR. DNA Structure and Function . Academic Press; London: 1994
  • 4 Dowhan W. Annual Review of Biochemistry 1997; 66: 199
  • 5 Oumzil K, Benizri S, Tonelli G, Staedel C, Appavoo A, Chaffanet M, Navailles L, Barthélémy P. ChemMedChem 2015; 10: 1797
  • 6 Yu X, Liu Z, Janzen J, Chafeeva I, Horte S, Chen W, Kainthan RK, Kizhakkedathu JN, Brooks DE. Nat. Mater. 2012; 11: 468
  • 7 Jain MK, Tao W, Rogers J, Arenson C, Eibl H, Yu BZ. Biochemistry 1991; 30: 10256
  • 8 Masuyer G, Jabeen T, Öberg CT, Leffler H, Nilsson UJ, Acharya KR. FEBS J. 2012; 279: 193
  • 9 Sosa M, Saha A, Giner-Sorolla A, Hadden E, Hadden JW. Ann. N. Y. Acad. Sci. 1993; 685: 458
  • 10 Rodriguez MJ, Vasudevan V, Jamison JA, Borromeo PS, Turner WW. Bioorg. Med. Chem. Lett. 1999; 9: 1863
  • 11 Marugg JE, Burik A, Tromp M, van der Marel GA, van Boom JH. Tetrahedron Lett. 1986; 27: 2271
  • 12 Bonnet H. Justus Liebigs Ann. Chem. 1857; 104: 337
    • 13a Mushika Y, Hata T, Mukaiyama T. Bull. Chem. Soc. Jpn. 1971; 44: 232
    • 13b Ramirez F, Glaser SL, Stern P, Ugi I, Lemmen P. Tetrahedron 1973; 29: 3741
    • 13c Ramirez F, Marecek JF, Okazaki H. J. Am. Chem. Soc. 1976; 98: 5310
  • 14 Domon K, Puripat M, Fujiyoshi K, Hatanaka M, Kawashima SA, Yamatsugu K, Kanai M. ACS Cent. Sci. 2020; 6: 283
  • 15 Hamasaki N, Kawamura H, Ohtsu N, Nakakoshi I, Ataka K, Oomori K, Kouno M. EP239357A2, 1987
  • 16 Clark VM, Kirby AJ. J. Am. Chem. Soc. 1963; 85: 3705
  • 17 Benkovic SJ, Schray KJ. J. Am. Chem. Soc. 1969; 91: 5653
  • 18 Baccolini G, Boga C, Micheletti G. Phosphorus, Sulfur, Silicon Relat. Elem. 2010; 185: 2303
  • 19 Wolfe AJ. Microbiol. Mol. Biol. Rev. 2005; 69: 12
  • 20 Standard Procedures for Phosphorylation of Alcohols: Methyl 4-(3-{[hydroxy(methoxy)phosphoryl]oxy}propoxy) Benzoate (23) A heat-gun-dried and argon-flushed test tube equipped with a magnetic stirrer bar was charged with 3-bromopyruvic acid (50.1 mg, 300 μmol, 1.0 equiv.) and diethyl ether (180 μL, 1.66 M). Then, a solution of trimethyl phosphite (37.2 mg, 300 μmol, 1.0 equiv.) in diethyl ether (180 μL, 1.66 M) was added dropwise at a gently reflux rate, and the reaction mixture was stirred at r.t. After 1 h, the solvent was removed under high vacuum, and the resulting dimethyl phosphoenolpyruvate was used without further purification. To the freshly-prepared dimethyl phosphoenolpyruvate (58.5 mg, 300 μmol, 3.0 equiv.) were added sequentially acetonitrile (1.0 mL, 0.10 M), substrate methyl 4-(3-hydroxypropoxy)benzene (21.0 mg, 100 μmol, 1.0 equiv.), and methyl nicotinate (13.7 mg, 100 μmol, 1.0 equiv.). The mixture was warmed to 60 °C and stirred for 6 h. Then the reaction mixture was cooled to r.t. and concentrated. After adding saturated aq. Na2CO3, the mixture was washed three times with diethyl ether. The aqueous layer was acidified with concentrated HCl to pH 1 and extracted five times with dichloromethane. The combined organic layers were dried over with Na2SO4, filtered, and concentrated to afford crude product, which was purified by preparative HPLC to afford the corresponding phosphorylated product 23 in 52% yield. 1H NMR (CDCl3, 400 MHz): δ = 7.95 ­(d, J = 8.7 Hz, 2 H), 6.88 (d, J = 8.7 Hz, 2 H), 4.21 (dt, J = 6.4, 6.4 Hz, 2 H), 4.10 (t, J = 6.4 Hz, 2 H), 3.86 (s, 3 H), 3.68 (d, J = 11.4 Hz, 3 H), 2.17–2.11 (m, 2 H). 13C NMR (CDCl3, 100 MHz): δ = 166.9, 162.4, 131.6, 122.7, 114.0, 64.1 (d, J = 4.8 Hz), 63.7, 54.0 (d, J = 5.7 Hz), 51.9, 29.9 (d, J = 6.7 Hz). 31P NMR (CDCl3, 159 MHz): δ = 1.6. ESI-MS: m/z = 303.1 [M – H]. HRMS: m/z calcd for [C12H16O7P]: 303.0639; found: 303.0639.
  • 21 This manuscript was posted on ChemRxiv: Fujiyoshi K, Kawashima S, Yamatsugu K, Kanai M. ChemRxiv 2021; reprint DOI: 10.26434/chemrxiv.14531847.v1.