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Synlett 2012; 23(20): 2951-2956
DOI: 10.1055/s-0032-1317622
letter
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Nuevamine Aza-Analogues by a Sequence: I-MCR–Aza-Diels–Alder–Pictet–Spengler

Alejandro Islas-Jácome
a   Departamento de Química, División de Ciencias Básicas e Ingeniería, Universidad Autónoma Metropolitana-Iztapalapa, San Rafael Atlixco 186, Col. Vicentina Iztapalapa, C. P. 09340, México D. F., México   Fax: +52(55)58044666   Email: egz@xanum.uam.mx
b   Departamento de Química, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Noria Alta S/N, Col. Noria Alta, C. P. 36050, Guanajuato, Guanajuato, México   Fax: +52(473)73200068168   Email: rociogm@ugto.mx
,
Luis E. Cárdenas-Galindo
b   Departamento de Química, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Noria Alta S/N, Col. Noria Alta, C. P. 36050, Guanajuato, Guanajuato, México   Fax: +52(473)73200068168   Email: rociogm@ugto.mx
,
Alberto V. Jerezano
c   Departamento de Química Orgánica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prol. Carpio y Plan de Ayala S/N, Col. Casco de Santo Tomás, C. P. 11340, México D. F., México
,
Joaquín Tamariz
c   Departamento de Química Orgánica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prol. Carpio y Plan de Ayala S/N, Col. Casco de Santo Tomás, C. P. 11340, México D. F., México
,
Eduardo González-Zamora*
a   Departamento de Química, División de Ciencias Básicas e Ingeniería, Universidad Autónoma Metropolitana-Iztapalapa, San Rafael Atlixco 186, Col. Vicentina Iztapalapa, C. P. 09340, México D. F., México   Fax: +52(55)58044666   Email: egz@xanum.uam.mx
,
Rocío Gámez-Montaño*
b   Departamento de Química, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Noria Alta S/N, Col. Noria Alta, C. P. 36050, Guanajuato, Guanajuato, México   Fax: +52(473)73200068168   Email: rociogm@ugto.mx
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Further Information

Publication History

Received: 03 September 2012

Accepted after revision: 24 October 2012

Publication Date:
23 November 2012 (online)

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Abstract

A series of nuevamine aza-analogues were prepared in moderate to good yields in two reaction steps. The synthetic strategy involves an isonitrile-based multicomponent reaction, including an aza-Diels–Alder cycloaddition and Pictet–Spengler reaction as postcondensation.

Key words

nuevamine aza-analogue - I-MCR - aza-Diels–Alder - S-oxidation - Pictet–Spengler cyclization
 

  • References and Notes

  • 4 Selvakumar J, Ramanathan RC. Org. Biomol. Chem. 2011; 9: 7643 ; and references cited therein
    CrossrefPubMedSearch in Google Scholar
    • 6a Bahajaj AA, Vernon JM, Wilson GD. J. Chem. Soc., Perkin Trans. 1 2001; 1446
    • 6b Hitchings GJ, Vernon JM. J. Chem. Soc., Perkin Trans. 1 1990; 1757
    • 6c Hitchings GJ, Vernon JM. J. Chem. Soc., Chem. Commun. 1988; 623
    • 6d Zamudio-Medina A, García-Gonzalez MC, Padilla J, González-Zamora E. Tetrahedron Lett. 2010; 51: 4837
      CrossrefSearch in Google Scholar
    • 8a El Kaim L, Gámez-Montaño R, Grimaud L, Ibarra-Rivera T. Chem. Commun. 2008; 11: 1350
      Search in Google Scholar
    • 8b Gámez-Montaño R, Ibarra-Rivera T, El Kaim L, Miranda LD. Synthesis 2010; 1285
      Thieme Connect
  • 9 Islas-Jácome A, González-Zamora E, Gámez-Montaño R. Tetrahedron Lett. 2011; 52: 5245
    CrossrefSearch in Google Scholar
  • 10 Procedure for the Synthesis of Pyrrolo[3,4-b]pyridin-5-ones 11a–d: Selected Compound 6-(3,4-Dimethoxyphenethyl)-2-benzyl-6,7-dihydro-3-morpholino-7-[(phenylthio)methyl]pyrrolo[3,4-b]pyridin-5-one (11a) 3,4-Dimethoxyphenethylamine (0.671 mmol, 1.0 equiv) and 2-thiophenylacetaldehyde (0.603 mmol, 0.9 equiv) were placed in a 10 mL sealed CEM DiscoverTM microwave reaction tube and diluted in 1.0 mL of dry toluene. Then, the mixture was irradiated (MW, 80 °C, 25 W) for 10 min and Sc(OTf)3 (0.0211 mmol, 0.03 equiv) was added. The mixture was irradiated (MW, 80 °C, 25 W) for 10 min, and 2-isocyano-1-morpholino-3-phenylpropan-1-one (0.805 mmol, 1.2 equiv) was added. The mixture was again irradiated (MW, 80 °C, 25 W), this time for 15 min, and maleic anhydride (0.805 mmol, 1.2 equiv) was added. Finally, this reaction mixture was irradiated (MW, 80 °C, 25 W) for 15 min, and the solvent was removed under reduced pressure. The crude was dissolved in CH2Cl2 (5.0 mL) and washed with a concentrated aq solution of NaHCO3 (3 × 25 mL) and with brine (3 × 25 mL). The organic layer was dried with Na2SO4, and the solvent was removed under vacuum. The residue was immediately purified using a silica gel chromatoflash (hexane–EtOAc = 2:1) to afford compound 11a (68%) as a pale yellow powder; mp 58–59 °C; Rf = 0.25 (hexane–EtOAc = 1:1). Spectral Data for Compound 11a 1H NMR (500 MHz, CDCl3): δ = 7.79 (s, 1 H, H-4), 7.25–7.13 (m, 10 H, HAr), 6.76–6.69 (m, 3 H, HAr), 4.51 (m, 1 H, H-7), 4.27 (d, J = 14.2 Hz, 1 H, H-10), 4.19 (d, J = 14.2 Hz, 1 H, H-10), 4.21–4.13 (m, 1 H, H-17), 3.83 (s, 3 H, H-25), 3.83–3.79 (m, 4 H, H-16), 3.78 (s, 3 H, H-26), 3.56 (dd, J = 14.1, 3.8 Hz, 2 H, H-27), 3.25–3.19 (m, 1 H, H-17), 2.96–2.89 (m, 1 H, H-18), 2.88–2.82 (m, 1 H, H-18), 2.82–2.80 (m, 4 H, H-15). 13C NMR (125 MHz, CDCl3): δ = 167.0 (C-5), 161.1 (C-2), 158.3 (C-8), 148.9 (C-23), 147.8 (C-3), 147.6 (C-22), 139.2 (C-11), 135.2 (C-28), 131.0 (C-19), 130.7 (C-12), 128.8 (C-13), 128.8 (C-29), 128.3 (C-30), 126.7 (C-14), 126.2 (C-31), 125.1 (C-9), 123.2 (C-4), 120.5 (C-20), 111.8 (C-21), 111.2 (C-19), 67.1 (C-16), 60.1 (C-7), 55.9 (C-25, C-26), 52.9 (C-15), 41.7 (C-17), 39.8 (C-10), 35.6 (C-27), 34.0 (C-18). FT-IR (film in CH2Cl2): 1691 (C=O) cm–1. HRMS: m/z calcd for C33H31N3O4S: 595.2505; found: 595.2507.
  • 12 Firestone RA, Harris EE, Reuter W. Tetrahedron 1967; 23: 943
    CrossrefSearch in Google Scholar
  • 13 Kato I, Higashimoto M, Tamura O, Ishibashi H. J. Org. Chem. 2003; 68: 7983
    CrossrefSearch in Google Scholar
  • 15 Ishibashi H, Kawanami H, Ikeda M. J. Chem. Soc., Perkin Trans. 1 1997; 817
  • 16 Procedure for the Synthesis of Nuevamine Aza-Analogues 6a–d: Selected Compound 6a To a stirred solution of S-oxide 4a (0.034 mmol, 1.0 equiv) in CH2Cl2 (1.0 mL) at 0 °C, drops of TFAA (0.172 mmol, 5.0 equiv) were added. After stirring at r.t. for 3 h, the solvent was removed under reduced pressure, and the crude was dissolved in CH2Cl2 (1.0 mL), and washed with an aq solution of NaHCO3 (3 × 10 mL) and with brine (3 × 10 mL). The organic layer was dried with Na2SO4, and the solvent was removed under vacuum. The residue was immediately purified using a silica gel chromatoflash (hexane–EtOAc = 1:1) to afford compound 6a (92%) as a pale pink powder; mp 72–74 °C; Rf = 0.15 (hexane–EtOAc = 1:1). Spectral Data for Compound 6a 1H NMR (500 MHz, CDCl3): δ = 7.84 (s, 1 H, H-9), 7.67 (s, 1 H, H-4), 7.27–7.16 (m, 5 H, HAr), 6.55 (s, 1 H, H-1), 4.67–4.63 (m, 1 H, H-6), 4.50 (d, J = 14.5 Hz, 1 H, H-20), 4.32 (d, J = 14.5 Hz, 1 H, H-20), 3.83–3.79 (m, 7 H, H-19, H-25), 3.67 (s, 3 H, H-26), 3.42–3.26 (m, 1 H, H-6), 3.06–2.99 (m, 1 H, H-5), 2.84–2.82 (m, 4 H, H-18), 2.76–2.72 (m, 1 H, H-5), 1.81 (s, 3 H, H-13). 13C NMR (125 MHz, CDCl3): δ = 167.7 (C-8), 163.5 (C-16), 161.0 (C-11), 148.0 (C-3), 147.7 (C-10), 147.5 (C-2), 139.6 (C-21), 129.6 (C-16), 128.9 (C-22), 128.3 (C-23), 126.2 (C-24), 124.6 (C-17), 123.7 (C-9), 123.1 (C-15), 111.2 (C-1), 109.9 (C-4), 67.2 (C-19), 63.1 (C-12), 55.9 (C-25), 55.8 (C-26), 53.0 (C-18), 40.0 (C-20), 34.7 (C-6), 29.0 (C-5), 27.9 (C-13). FT-IR (film in CH2Cl2): 1693 (C=O) cm–1. HRMS: m/z calcd for C33H29N3O4S: 485.2315; found: 485.2314.
  • 19 Maryanoff BE, Zhang H.-C, Cohen JH, Turchi IJ, Maryanoff CA. Chem. Rev. 2004; 104: 1431
    CrossrefPubMedSearch in Google Scholar