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Synlett 2014; 25(10): 1381-1384
DOI: 10.1055/s-0033-1338621
letter
© Georg Thieme Verlag Stuttgart · New York

First Total Synthesis of Murrastifoline B and an Improved Route to Murrastifoline F

Carsten Börger
Department Chemie, Technische Universität Dresden, Bergstraße 66, 01069 Dresden, Germany   Fax: +49(351)46337030   Email: hans-joachim.knoelker@tu-dresden.de
,
Arndt W. Schmidt
Department Chemie, Technische Universität Dresden, Bergstraße 66, 01069 Dresden, Germany   Fax: +49(351)46337030   Email: hans-joachim.knoelker@tu-dresden.de
,
Hans-Joachim Knölker*
Department Chemie, Technische Universität Dresden, Bergstraße 66, 01069 Dresden, Germany   Fax: +49(351)46337030   Email: hans-joachim.knoelker@tu-dresden.de
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Further Information

Publication History

Received: 17 March 2014

Accepted after revision: 31 March 2014

Publication Date:
03 April 2014 (online)

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Abstract

We report the first total synthesis of murrastifoline B and an improved route to murrastifoline F using a twofold palladium-catalyzed Buchwald–Hartwig amination as key step. The mono­meric carbazole and the biaryl precursor are also prepared via ­palladium-catalyzed coupling reactions.

Key words

alkaloids - catalysis - cyclization - natural products - palladium

Supporting Information

    for this article is available online at http://www.thieme-connect.com/ejournals/toc/synthesis.
  • Supporting Information
 

  • References and Notes

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  • 24 Experimental Procedure for the Twofold Buchwald–Hartwig Coupling to Murrastifoline B (2) A solution of the aminocarbazole 6 (19.1 mg, 0.061 mmol), the bistriflate 5 (30.2 mg, 0.061 mmol), Pd2(dba)3 (11.2 mg, 0.012 mmol), XantPhos (14.1 mg, 0.024 mmol), and K3PO4 (61.9 mg, 0.292 mmol) in o-xylene (3 mL) was heated at 130 °C for 64 h. The reaction mixture was diluted with EtOAc and a sat. aq. solution of NH4Cl was added. The aqueous layer was separated and extracted three times with EtOAc. The combined organic layers were washed with brine and dried over MgSO4. Removal of the solvent and purification of the residue by flash chromatography on silica gel (isohexane–EtOAc, 6:1) afforded murrastifoline B (2); yield 16.4 mg (66%); colorless crystals; mp 58.5–59 °C (lit.7 oil). UV (MeOH): λ = 229 (sh), 242, 291, 335 nm. IR (ATR): ν = 3407, 3055, 2923, 2852, 1692, 1624, 1582, 1542, 1502, 1453, 1419, 1395, 1323, 1277, 1222, 1134, 1104, 1037, 1014, 991, 952, 909, 827, 765, 746, 698, 659, 638, 619 cm–1. 1H NMR (600 MHz, acetone-d 6): δ = 2.55 (s, 3 H), 3.63 (s, 3 H), 4.06 (s, 3 H), 6.89 (s, 1 H), 7.07 (d, J = 1.6 Hz, 1 H), 7.21–7.25 (m, 3 H), 7.35–7.37 (m, 1 H), 7.46 (ddd, J = 8.3, 7.1, 1.2 Hz, 1 H), 7.66 (dd, J = 1.3, 0.8 Hz, 1 H), 7.68 (dt, J = 8.2, 0.8 Hz, 1 H), 7.84 (m, 1 H), 8.15–8.17 (m, 2 H), 10.61 (br s, 1 H). 13C NMR and DEPT (150 MHz, acetone-d 6): δ = 21.68 (CH3), 56.10 (CH3), 56.24 (CH3), 108.13 (CH), 110.82 (CH), 111.20 (CH), 112.30 (CH), 113.11 (CH), 113.36 (CH), 119.88 (CH), 120.16 (CH), 120.69 (CH), 121.29 (CH), 123.8 (C), 124.4 (C), 126.45 (CH), 126.56 (CH), 129.97 (C), 130.06 (C), 132.77 (C), 141.2 (C), 144.0 (C), 146.39 (C), 147.82 (C); 3 C signals are missing. ESI-MS (10 V): m/z = 407 [M + H]+.
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  • 27 Murrastifoline F (3) Colorless crystals; 288–289 °C (lit.9 289 °C). UV (MeOH): λ = 227, 242 (sh), 260 (sh), 287 (sh), 351 nm. IR (ATR): ν = 3055, 2923, 2852, 1653, 1592, 1500, 1460, 1444, 1395, 1318, 1281, 1227, 1192, 1170, 1104, 1072, 1041, 938, 822, 745, 695, 637, 606 cm–1. 1H NMR (300 MHz, CDCl3): δ = 2.30 (s, 3 H), 2.40 (s, 3 H), 3.80 (s, 3 H), 3.91 (s, 3 H), 6.50–6.56 (m, 3 H), 6.69–6.82 (m, 4 H), 6.83 (s, 1 H), 6.94 (s, 1 H), 7.33 (t, J = 7.6 Hz, 1 H), 7.53 (d, J = 7.6 Hz, 1 H), 7.73 (d, J = 7.0 Hz, 1 H). ESI-MS (25 V): m/z = 438 [M + NH4]+.