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Synlett 2021; 32(03): 295-298
DOI: 10.1055/s-0040-1705959
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Synthesis of Optically Active Maresin 2 and Maresin 2n-3 DPA

Narihito Ogawa  ∗
a   Department of Applied Chemistry, Meiji University, 1-1-1 Higashimita, Tama-ku, Kawasaki, Kanagawa 214-8571, Japan   Email: narihito@meiji.ac.jp
,
Takahito Amano
a   Department of Applied Chemistry, Meiji University, 1-1-1 Higashimita, Tama-ku, Kawasaki, Kanagawa 214-8571, Japan   Email: narihito@meiji.ac.jp
,
Yuichi Kobayashi
b   Organization for the Strategic Coordination of Research and Intellectual Properties, Meiji University, 1-1-1 Higashimita, Tama-ku, Kawasaki, Kanagawa 214-8571, Japan
› Author AffiliationsThis work was supported by Research Project Grant (B) by Institute of Science and Technology Meiji University (N.O.).
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Abstract

Maresins are among the most potent antiinflammatory lipid metabolites. We report stereoselective syntheses of maresin 2 and maresin 2n-3 DPA. The anti-diol was constructed through epoxide ring opening of an optically active β,γ-epoxy aldehyde, synthesized in situ by Swern oxidation of the corresponding alcohol. Finally, the target compounds were synthesized through a Sonogashira coupling of a C9–C22 iodide and methyl (Z)-oct-4-en-7-ynoate or methyl oct-7-ynoate, respectively.

Key words

maresins - asymmetric synthesis - trienes - Swern oxidation

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0040-1705959.
  • Supporting Information


Publication History

Received: 02 September 2020

Accepted after revision: 02 October 2020

Article published online:
02 November 2020

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  • References and Notes

  • 2 Deng B, Wang C.-W, Arnardottir HH, Li Y, Cheng C.-YC, Dalli J, Serhan CN. PLoS One 2014; 9: e102362
    CrossrefPubMedSearch in Google Scholar
  • 3 Dalli J, Colas RA, Serhan CN. Sci. Rep. 2013; 3: 1940 ; corrigendum: Sci. Rep. 2014, 4, 6726
    CrossrefPubMedSearch in Google Scholar
  • 7 Kobayashi Y, Morita M, Ogawa N, Kondo D, Tojo T. Org. Biomol. Chem. 2016; 14: 10667
    CrossrefPubMedSearch in Google Scholar
  • 8 The double bond of the product was obtained with high selectivity. The corresponding olefin isomer could not be detected by 1H NMR spectroscopy.
  • 9 Druais V, Hall MJ, Corsi C, Wendeborn SV, Meyer C, Cossy J. Org. Lett. 2009; 11: 935
    CrossrefPubMedSearch in Google Scholar
  • 10 Banfi L, Basso A, Guanti G, Riva R. Tetrahedron 2006; 62: 4331
    CrossrefSearch in Google Scholar
  • 11 Matsumura K, Hashiguchi S, Ikariya T, Noyori R. J. Am. Chem. Soc. 1997; 119: 8738
    CrossrefSearch in Google Scholar
  • 12 Gao Y, Hanson RM, Klunder JM, Ko SY, Masamune H, Sharpless KB. J. Am. Chem. Soc. 1987; 109: 5765
    CrossrefSearch in Google Scholar
    • 13a Miwa K, Aoyama T, Shioiri T. Synlett 1994; 107
    • 13b Colvin EW, Hamill BJ. J. Chem. Soc., Chem. Commun. 1973; 151
  • 15 Afonso CM, Barros MT, Maycock CD. J. Chem. Soc., Perkin Trans. 1 1987; 1221
    Crossref
  • 16 Boland W, Schroer N, Sieler C, Feigel M. Helv. Chim. Acta 1987; 70: 1025
    CrossrefSearch in Google Scholar
  • 17 Maresin 2 (2) Cu(OAc)2 (101 mg, 0.55 mmol) and AgNO3 (103 mg, 0.61 mmol) were added to a slurry of Zn (1.08 g, 16.5 mmol) in H2O (1 mL), and the mixture was stirred for 1 h then filtered by using a Hirsch funnel. The remaining Zn solids were washed successively with H2O (1 mL), MeOH (1 mL), acetone (1 mL), and Et2O (1 mL). The activated Zn solids were transferred to 1:1 MeOH–H2O (2 mL), and a solution of alkyne 25 (30.7 mg, 0.082 mmol) in MeOH (1 mL) was added to the suspension of activated Zn. The mixture was stirred for 11 h then filtered through a plug of cotton that was washed with EtOAc. The mixture was concentrated, and the residue was semi-purified by chromatography (silica gel), ready for the next reaction. To an ice-cold solution of the resulting ester in MeOH (1 mL) and THF (1 mL) was added 2 N aq LiOH (0.82 mL, 1.64 mmol). After 5 h at 0 °C, citrate–phosphate buffer (pH 5.0, 40 mL) was added, and the resulting mixture was extracted with EtOAc (×7). The combined extracts were dried (MgSO4) and concentrated, and the residue was purified by chromatography (silica gel, hexane–EtOAc) to give maresin 2 (2) as a pale-yellow oil; yield: 18.5 mg (63% from 25); Rf = 0.61 (hexane–EtOAc, 1:2); [α]D 24 +45.8 (c 0.37, MeOH). IR (neat): 3454, 2064, 1727, 1652 cm–1. 1H NMR (400 MHz, CD3OD): δ = 0.86 (t, J = 7.4 Hz, 3 H), 1.97 (quin, J = 7.4 Hz, 2 H), 2.02–2.13 (m, 1 H), 2.20–2.33 (m, 5 H), 2.70 (t, J = 6.2 Hz, 2 H), 2.89 (t, J = 6.0 Hz, 2 H), 3.47 (dt, J = 8.4, 5.0 Hz, 1 H), 3.92 (dd, J = 7.0, 5.0 Hz, 1 H), 4.84 (s, 3 H, overlapped with the residue from CD3OD), 5.15–5.43 (m, 7 H), 5.72 (dd, J = 14.8, 7.0 Hz, 1 H), 5.94 (t, J = 11.0 Hz, 1 H), 6.16 (dd, J = 14.8, 11.0 Hz, 1 H), 6.26 (dd, J = 14.8, 11.0 Hz, 1 H), 6.48 (dd, J = 14.8, 11.0 Hz, 1 H). 13C NMR (100 MHz, CD3OD): δ = 14.7, 21.5, 23.8, 26.6, 27.0, 31.8, 35.0, 75.8, 76.3, 127.1, 128.2, 129.1, 129.5, 129.7, 129.8, 131.0, 131.2, 132.7, 133.6, 133.7, 133.8, 177.1. HRMS (FD): m/z [M+] calcd for C22H32O4: 360.23006; found: 360.23029. UV (MeOH): λmax = 262, 274, 282 nm.