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Synlett 2016; 27(17): 2497-2499
DOI: 10.1055/s-0035-1562776
letter
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Ieodomycin D

Jørn Eivind Tungen
Department of Pharmaceutical Chemistry, School of Pharmacy, University of Oslo, P.O. Box 1068, Blindern, N-0316 Oslo, Norway   Email: anders.vik@farmasi.uio.no
,
Marius Aursnes
Department of Pharmaceutical Chemistry, School of Pharmacy, University of Oslo, P.O. Box 1068, Blindern, N-0316 Oslo, Norway   Email: anders.vik@farmasi.uio.no
,
Anders Vik*
Department of Pharmaceutical Chemistry, School of Pharmacy, University of Oslo, P.O. Box 1068, Blindern, N-0316 Oslo, Norway   Email: anders.vik@farmasi.uio.no
› Author Affiliations
Further Information

Publication History

Received: 15 April 2016

Accepted after revision: 17 June 2016

Publication Date:
14 July 2016 (online)

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Abstract

A synthesis of the marine natural product ieodomycin D has been achieved in seven steps and 16% overall yield from commercially available pyridinium-1-sulfonate. The key synthetic step was a B-alkyl Suzuki–Miyaura cross-coupling reaction. The enantiomer of ieodomycin D was also prepared using the same synthetic strategy.

Key words

ieodomycin D - B-alkyl Suzuki–Miyaura reaction - marine natural product - antibacterial effects - 5-bromopenta-2,4-dienal

Supporting Information

    Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0035-1562776.
  • Supporting Information
 

  • References and Notes

  • 2 Mondol MA. M, Kim JH, Lee MA, Tareq FS, Lee H.-S, Lee Y.-J, Shin HJ. J. Nat. Prod. 2011; 74: 1606
    CrossrefSearch in Google Scholar
  • 4 Chinnababu B, Reddy SP, Reddy DK, Rao DC, Venkateswarlu Y. Synthesis 2012; 44: 311
    Thieme ConnectSearch in Google Scholar
  • 5 Tungen JE, Aursnes M, Hansen TV. Tetrahedron 2014; 70: 3793
    CrossrefSearch in Google Scholar
  • 8 Nolsøe JM. J, Aursnes M, Tungen JE, Hansen TV. J. Org. Chem. 2015; 80: 5377
    CrossrefSearch in Google Scholar
    • 9a Becher J. Org. Synth. 1980; 59: 79
      Search in Google Scholar
    • 9b Soullez D, Ple G, Duhamel L. J. Chem. Soc., Perkin Trans. 1 1997; 1639
  • 10 Vicart N, Castet-Cailabet D, Ramondenc Y, Plé G, Duhamel L. Synlett 1998; 411
    Thieme Connect
  • 11 Okada M, Miyagawa H, Ueno T. Biosci., Biotechnol., Biochem. 1999; 63: 1253
    CrossrefSearch in Google Scholar
  • 12 Experimental Procedure and Analytical Data for Compound 11 (R)-tert-Butyldimethyl(pent-4-en-2-yloxy)silane (10, 1.0 equiv) was dissolved in dry THF (4.5 mL/mmol 10) and added to a solution of 9-BBN-H (2.0 equiv, 0.50 M in THF) at 0 °C under an argon atmosphere. After stirring for 90 min, the ice-bath was removed, and the mixture was allowed to stir for an additional 90 min. Then a freshly prepared solution of methyl (2E,4E)-5-bromopenta-2,4-dienoate (9, 1.10 equiv) in dry DMF (4.5 mL/mmol 10) was added, followed by an aqueous solution of K3PO4 (0.68 mL/mmol 10, 3.0 M). Pd(dppf)Cl2·CH2Cl2 (0.05 equiv) was added against a gentle stream of argon, and the mixture was stirred at room temperature for 20 h. To the mixture was added sat. aq NaHCO3 and extracted with Et2O (3×). The combined organic layers were washed with brine, dried (Na2SO4), and evaporated in vacuo. The residue was purified by flash chromatography on silica gel (5% EtOAc in heptane) to afford the desired product 11 as a colorless oil in 77% yield (20 mg). TLC (heptane–EtOAc, 19:1, UV light): R f = 0.26; [α]D 20 –11 (c 0.6, CHCl3), lit.4 [α]D 20 –11.6 (c 0.6, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 7.26 (dd, J = 15.4, 9.9 Hz, 1 H), 6.23–6.06 (m, 2 H), 5.79 (d, J = 15.4 Hz, 1 H), 3.83–3.73 (m, 1 H), 3.73 (s, 3 H), 2.16 (m, 2 H), 1.57–1.33 (m, 4 H), 1.11 (d, J = 6.1 Hz, 3 H), 0.88 (s, 9 H), 0.04 (d, J = 2.1 Hz, 6 H). 13C NMR (101 MHz, CDCl3): δ = 167.9, 145.5, 144.8, 128.6, 118.9, 68.5, 51.6, 39.3, 33.1, 26.0 (3 C), 26.0, 24.0, 18.4, –4.2, –4.7. HRMS (EI): m/z calcd for C17H32O3Si [M]+: 312.2121; found: 312.2110.
  • 13 Experimental Procedure and Analytical Data for Ieodomycin D (4) The methylester 12 (1.0 equiv) was dissolved in a mixture of THF (50 mL/mmol 12), MeOH (50 mL/mmol 12) and water (25 mL/mmol 12), cooled in an ice bath and added solid LiOH (30 equiv). The ice bath was then removed, and the mixture was stirred for 6 h. MeOH and THF were removed in vacuo, and to the residue was added sat. aq NaH2PO4 and extracted with EtOAc (3×). The combined organic layers were dried over Na2SO4 and evaporated in vacuo to give the desired product as a colorless oil (96% yield, 20 mg) which solidified in the freezer. [α]D 20 –5 (c 1.3, CHCl3). 1H NMR (400 MHz, CD3OD); δ = 7.25 (dd, J = 15.3, 10.3 Hz, 1 H), 6.32–6.12 (m, 2 H), 5.78 (d, J = 15.4 Hz, 1 H), 3.81–3.66 (m, 1 H), 2.24–2.16 (m, 2 H), 1.63–1.36 (m, 4 H), 1.15 (d, J = 6.2 Hz, 3 H). 13C NMR (101 MHz, CD3OD): δ = 170.8, 146.9, 145.7, 129.8, 120.5, 68.3, 39.6, 33.9, 26.1, 23.5. HRMS (EI): m/z calcd for C10H16O3 [M]+: 184.1099; found: 184,1091.
  • 14 Souris C. Sequential photochemical and catalytic transformations: towards the total synthesis of polyenic natural products.. University of Vienna, 2014 , Ph.D. thesis.
    Search in Google Scholar
  • 18 Zheng CJ, Yoo J.-S, Lee T.-G, Cho H.-Y, Kim Y.-H, Kim W.-G. FEBS Lett. 2005; 579: 5157
    CrossrefSearch in Google Scholar