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Synlett 2011(4): 565-568  
DOI: 10.1055/s-0030-1259521
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Studies towards the Total Asymmetric Synthesis of the Pentacyclic Indole Alkaloid Arboflorine: Asymmetric Synthesis of a Key Intermediate

Yu Dua, Hui-Ying Huangb, Hui Liua, Yuan-Ping Ruana, Pei-Qiang Huang*a
a Department of Chemistry and Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005, P. R. of China
Fax: +86(592)2186400; e-Mail: pqhuang@xmu.edu.cn;
b School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, P. R. of China
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Publication History

Received 27 November 2010
Publication Date:
27 January 2011 (online)

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Abstract

The synthesis of a plausible key intermediate for a biomimetic asymmetric synthesis of indole alkaloid arboflorine is described. The method featured the use of Ellman’s sulfinamide chemistry for the establishment of the first chiral center, and the Polonovski-Potier reaction for the formation of the α-aminonitrile moiety.

Key words

indole alkaloids - biogenetic pathway - intermediate - Polonovski-Potier reaction - Ellman’s sulfinamide

    References and Notes

  • For some recent reviews, see:
  • 1a Kam T.-S. Lim K.-H. Alkaloids of Kopsia, In The Alkaloids: Chemistry and Biology   Vol. 66:  Cordell GA. Academic Press; Amsterdam: 2008.  p.1-111  
    Google Scholar
  • 1b Ishikura M. Yamada K. Abe T. Nat. Prod. Rep.  2010,  27:  1630 
    Google Scholar
  • 1c Li S.-M. Nat. Prod. Rep.  2010,  27:  57 
    Google Scholar
  • 2 Lim K.-H. Kam T.-S. Org. Lett.  2006,  8:  1733 
    CrossrefGoogle Scholar
  • 3 Huang P.-Q. Synlett  2006,  1133 
    Article in Thieme ConnectGoogle Scholar
  • 4a Xiao K.-J. Liu L.-X. Huang P.-Q. Tetrahedron: Asymmetry  2009,  20:  1181 
    Google Scholar
  • 4b Lin G.-J. Huang P.-Q. Org. Biomol. Chem.  2009,  7:  4491 
    Google Scholar
  • 4c Zheng X. Chen G. Ruan Y.-P. Huang P.-Q. Sci. China, Ser. B: Chem.  2009,  52:  1631 
    Google Scholar
  • 4d Yang R.-F. Huang P.-Q. Chem. Eur. J.  2010,  16:  10319 
    Google Scholar
  • 4e Xiao K.-J. Wang Y. Ye K.-Y. Huang P.-Q. Chem. Eur. J.  2010,  16:  12792 
    Google Scholar
  • 5a Liu L.-X. Xiao K.-J. Huang P.-Q. Tetrahedron  2009,  52:  3834 
    Google Scholar
  • 5b Fu R. Du Y. Li Z.-Y. Xu W.-X. Huang P.-Q. Tetrahedron  2009,  65:  9765 
    Google Scholar
  • 5c Fu R. Chen J. Guo L.-C. Ruan Y.-P. Huang P.-Q. Org. Lett.  2009,  11:  5242 
    Google Scholar
  • 5d Fu R. Ye J.-L. Dai X.-J. Ruan Y.-P. Huang P.-Q. J. Org. Chem.  2010,  75:  4230 
    Google Scholar
  • 5e Zheng X. Zhu W.-F. Huang P.-Q. Sci. China, Ser. B: Chem.  2010,  53:  1914 
    Google Scholar
  • 6a Li Z.-P. Li C.-J. Eur. J. Org. Chem.  2005,  3173 
    Google Scholar
  • 6b Baslé O. Li C.-J. Green Chem.  2007,  9:  1047 
    Google Scholar
  • 6c Li C.-J. Acc. Chem. Res.  2009,  42:  335 
    Google Scholar
  • 7a Grierson D. Org. React. (N.Y.)  1990,  39:  85 
    Google Scholar
  • 7b Polonovski M. Bull. Soc. Chim. Belg.  1930,  39:  1 
    Google Scholar
  • 7c Potier P. Annu. Proc. Phytochem. Soc. Eur.  1980,  17:  159 
    Google Scholar
  • 8a Ellman JA. Owens TD. Tang TP. Acc. Chem. Res.  2002,  35:  984 
    Google Scholar
  • 8b Ellman JA. Pure Appl. Chem.  2003,  75:  39 
    Google Scholar
  • 8c Senanayake CH. Krishnamurthy D. Lu Z.-H. Han Z. Gallon E. Aldrichimica Acta  2005,  38:  93 
    Google Scholar
  • 8d Daniel M. Stockman RA. Tetrahedron  2006,  62:  8869 
    Google Scholar
  • 9 Chelucci G. Baldino S. Chessa S. Pinna GA. Soccolini F. Tetrahedron: Asymmetry  2006,  17:  3163 
    CrossrefGoogle Scholar
  • 10a Liu G. Cogan DA. Owens TD. Tang TP. Ellman JA. J. Org. Chem.  1999,  64:  1278 
    Google Scholar
  • 10b Cogan DA. Ellman JA. J. Am. Chem. Soc.  1999,  121:  268 
    Google Scholar
  • 10c Davis FA. Zhang Y. Andemichael Y. Fang T. Fanelli DL. Zhang H. J. Org. Chem.  1999,  64:  1403 
    Google Scholar
  • 11a Kuehne ME. Xu F. J. Org. Chem.  1997,  62:  7950 
    Google Scholar
  • 11b Schkeryantz JM. Woo JCG. Siliphaivanh P. Depew KM. Danishefsky SJ. J. Am. Chem. Soc.  1999,  121:  11964 
    Google Scholar
  • 12 For an alternative method, see: Johansen MB. Kerr MA. Org. Lett.  2010,  12:  4956 
    CrossrefPubMedGoogle Scholar
  • 13 Fry EM. Beisler JA. J. Org. Chem.  1970,  35:  2809 
    CrossrefGoogle Scholar
  • 14 Passarella D. Martinelli M. Llor N. Amat M. Bosch J. Tetrahedron  1999,  55:  14995 
    CrossrefGoogle Scholar
  • 15a Murahashi SI. Komiya N. Terai H. Angew. Chem. Int. Ed.  2005,  44:  6931 
    Google Scholar
  • 15b Murahashi SI. Nakae T. Terai H. Komiya N. J. Am. Chem. Soc.  2008,  130:  11005 
    Google Scholar
  • 16a Grierson DS. Harris M. Husson H.-P. J. Am. Chem. Soc.  1980,  102:  1064 
    Google Scholar
  • 16b Grierson DS. Vuilhorgne M. Husson H.-P. J. Org. Chem.  1982,  47:  4439 
    Google Scholar
  • 16c Sundberg RJ. Grierson DS. Husson H.-P. J. Org. Chem.  1984,  49:  2400 
    Google Scholar
  • 17 Bonjoch J. Solé D. García-Rubio S. Bosch J. J. Am. Chem. Soc.  1997,  119:  7230 
    Google Scholar
  • 19 Agami C. Couty F. Evano G. Org. Lett.  2000,  2:  2085 
    CrossrefGoogle Scholar
18

All new compounds gave satisfactory analytical and spectral data.
Experimental Procedure for the Synthesis of the Key Intermediate 28: A solution of MCPBA (72%, 84 mg, 0.35 mmol) in CH2Cl2 (1 mL) was added dropwise to a solution of compound 25 (138 mg, 0.25 mmol) in CH2Cl2 (1.5 mL) at 0 ˚C. After stirring at 0 ˚C for 1 h, K2CO3 (70 mg, 0.5 mmol) was added. After stirring for an additional 1 h at 0 ˚C, the mixture was filtered through celite. The residue was purified by flash column chromatography on silica gel (R f 0.18, eluent: CH2Cl2-MeOH, 15:1) to give N-oxide 26 (140 mg, 98%), which was dissolved in anhyd CH2Cl2 (2.0 mL) and cooled to 0 ˚C. TFAA (0.07 mL, 0.5 mmol) was added. After being stirred for 30 min at 0 ˚C, an aqueous solution (0.5 mL) of KCN (65 mg, 1.0 mmol) was added, and the solution was buffered to pH 4 by addition of AcOH and NaOAc. After stirring for 1 h at 0 ˚C, the mixture was basified with K2CO3 and extracted with CH2Cl2 (3 × 3 mL). The combined extracts were successively washed with H2O (2 mL) and brine (1 mL), dried over anhyd Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on neutral Al2O3 (R f = 0.4, eluent: EtOAc-n-hexane, 1:4) to give compound 28 (108 mg, 74% from 25) as a white amorphous solid. IR (film): 3370, 2978, 2934, 2216 (w, CN), 1730 (s), 1511, 1458, 1392, 1367, 1328, 1248, 1169, 1133 cm-¹. ¹H NMR (400 MHz, CDCl3; diastereomeric mixture and rotamers): δ = 1.25 (m, 3 H, CH2CH 3), 1.33 (m, 3 H, CHCH 3), 1.44 [m, 9 H, C(CH3)3], 1.65 [s, 9 H, C(CH3)3], 2.08-2.18 (m, 1 H, C=CHCH 2), 2.26-2.44 (m, 1 H, C=CHCH 2), 2.53-2.63 (m, 1 H, C=CHCH2CH 2), 2.70-2.95 (m, 5 H, C=CHCH2CH 2, ArCH 2CH 2N), 4.03 (s, 2 H, CH2CO2), 4.16 (m, 2 H, CH 2CH3), 4.27 (s, 1 H, CHCN), 4.22-4.38 (m, 1 H, CHCH3), 4.57 (br s, 1 H, NH), 5.86, 5.89 (br s, 1 H, C=CH), 7.24 (t,

J = 7.3 Hz, 1 H, ArH), 7.29 (t, J = 7.3 Hz, 1 H, ArH), 7.53 (d, J = 7.8 Hz, 1 H, ArH), 8.09 (d, J = 7.8 Hz, 1 H, ArH). ¹³C NMR (100 MHz, CDCl3; diastereomeric mixture and rotamers): d = 14.2, 22.4, 22.5, 25.1, 25.2, 28.1, 28.25, 28.29, 28.33, 28.7, 29.6, 33.17, 33.2, 45.6, 45.65, 47.5, 52.4, 55.2, 55.3, 60.8, 79.8, 80.1, 84.0, 115.7, 115.9, 116.1, 118.0, 118.1, 118.2, 122.5, 124.2, 124.449, 124.458, 129.2, 129.7, 129.8, 134.08, 134.14, 135.8, 150.4, 155.3, 170.12, 170.18. HRMS: m/z [M + Na+] calcd for C32H44N4NaO6: 603.3159; found: 603.3153.