Towards Total Synthesis of
Communesins and Perophoramidine: Unexpected Cascade Reaction
of Michael-Mannich-Mannich Additions

Haoxing Wu; Xue Xiao; Yong Qin

doi:10.1055/s-0030-1259705

LETTER

Towards Total Synthesis of Communesins and Perophoramidine: Unexpected Cascade Reaction of Michael-Mannich-Mannich Additions

Haoxing Wu, Xue Xiao, Yong Qin*
Department of Medicinal Natural Products, Key Laboratory of Drug Targeting and Drug Delivery Systems of the Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, P. R. of China
Fax: +86(28)85503842; e-Mail: yongqin@scu.edu.cn;

Abstract

Alle Artikel dieser Rubrik

Abstract

A new type of chiral amidinobenzodiene 5 was prepared from isatin in ten steps. While attempting to prepare the core structure from 5 and tryptamine derivative 17 via a hetero Diels-Alder reaction for the total synthesis of communesin and perophoramidine, we observed an unexpected three-step, one-pot cascade reaction of Michael-Manich-Manich additions. The cascade reaction between 5 and 17 yielded diasteromers 21a and 21b with a complex polycyclic skeleton of 2,3,4,5-diindolinohexahydropyrrole in 76% yield and a ratio of 3:1. The stereochemistry of 21a was confirmed by X-ray crystal-structural analysis.

Key words

communesin - perophoramidine - cascade reaction - Michael addition - Mannich addition

Volltext

Referenzen

References and Notes

1 Numata A. Takahashi C. Ito Y. Takada T. Kawai K. Usami Y. Matsumura E. Imachi M. Ito T. Hasegawa T. Tetrahedron Lett. 1993, 34: 2355

2a Dalsgaard PW. Blunt JW. Munro MHG. Frisvad JC. Christophersen C. J. Nat. Prod. 2005, 68: 258

2b Jadulco R. Edrada RA. Ebel R. Berg A. Schaumann K. Wray V. Steube K. Proksch P. J. Nat. Prod. 2004, 67: 78

2c Hayashi H. Matsumoto H. Akiyama K. Biosci. Biotechnol. Biochem. 2004, 68: 753

3 Verbitski SM. Mayne CL. Davis RA. Concepcion GP. Ireland CM. J. Org. Chem. 2002, 67: 7124

4a Evans MA. Sacher JR. Weinreb SM. Tetrahedron 2009, 65: 6712

4b George JH. Adlington RM. Synlett 2008, 2093

4c Siengalewicz P. Gaich T. Mulzer J. Angew. Chem. Int. Ed. 2008, 47: 8170

4d Crawley S. Funk RL. Org. Lett. 2006, 8: 3995

4e Seo JH. Artman GD. Weinreb SM. J. Org. Chem. 2006, 71: 8891

4f Yang J. Song H. Xiao X. Wang J. Qin Y. Org. Lett. 2006, 8: 2187

4g May JA. Stoltz BM. Tetrahedron 2006, 62: 5262 ; and references cited therein

4h Crawley S. Funk RL. Org. Lett. 2003, 5: 3169

4i Artman GD. Weinreb SM. Org. Lett. 2003, 5: 1523

4j May JA. Zeidan RK. Stoltz BM. Tetrahedron Lett. 2003, 44: 1203

5a Fuchs JR. Funk RL. J. Am. Chem. Chem. 2004, 126: 5068

5b Sabahi A. Novikov A. Rainier JD. Angew. Chem. Int. Ed. 2006, 45: 4317

6a Yang J. Wu HX. Shen LQ. Qin Y. J. Am. Chem. Soc. 2007, 129: 13794

6b Liu P. Seo JH. Weinreb SM. Angew. Chem. Int. Ed. 2010, 49: 2000

6c Seo JH. Liu P. Weinreb SM. J. Org. Chem. 2010, 75: 2667

7 Zuo ZhW. Xie WQ. Ma DW. J. Am. Chem. Soc. 2010, 132: 13226

8 Wu HX. Xue F. Xiao X. Qin Y. J. Am. Chem. Soc. 2010, 132: 14052

9 Somei M. Yamada F. Kunimoto M. Kaneko C. Heterocycles 1984, 22: 797

10

Analytical Data
Compound 21a: ^¹H NMR (400 MHz, CDCl₃): δ = 0.32 (br, 1 H), 1.60-1.64 (m, 1 H), 1.74 (d, J = 7.6 Hz, 3 H), 2.04-2.12 (m, 1 H), 2.64-2.72 (m, 1 H), 2.69 (s, 3 H), 3.18-3.33 (m, 2 H), 3.72-3.79 (m, 1 H), 3.94 (s, 3 H), 4.25-4.29 (m, 1 H), 4.74-4.81 (m, 2 H), 5.16 (br, 1 H), 5.40 (s, 1 H), 5.62-5.67 (m, 2 H), 6.50 (t, J = 6.8 Hz, 1 H), 6.61 (t, J = 8.0 Hz, 1 H), 6.71 (d, J = 6.8 Hz, 1 H), 6.92 (t, J = 7.6 Hz, 2 H), 7.17 (t, J = 7.6 Hz, 2 H), 7.31-7.34 (m, 1 H), 7.39-7.43 (m, 2 H), 7.53-7.56 (m, 5 H), 7.65-7.74 (m, 4 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 21.74, 29.32, 29.33, 30.55, 34.19, 34.20, 36.04, 52.09, 52.10, 54.70, 69.23, 72.65, 92.73, 99.60, 99.73, 112.95, 113.43, 121.13, 122.66, 122.67, 123.75, 124.77, 126.83, 127.48, 127.50, 127.51 127.78, 127.79, 127.85, 128.11, 128.17, 128.43, 128.44, 128.45, 128.46, 129.50, 130.86, 132.19, 133.42, 133.48, 137.03, 144.82, 151.73, 153.36, 154.89, 167.61. HRMS: m/z [M + H⁺] calcd for C₄₆H₄₃N₄O₆: 747.3183; found: 747.3142. IR (KBr): 3463, 2950, 2875, 1712, 1608, 1446, 1393, 1208, 716 cm^-¹. [α]_D ^²0 +1.98 (c 1.0, CHC1₃).
Compound 21b: ^¹H NMR (400 MHz, CDCl₃): δ = 1.57 (s, 3 H), 1.71 (d, J = 6.8 Hz, 3 H), 1.80-1.84 (m, 1 H), 2.05-2.12 (m, 1 H), 2.60-2.68 (m, 1 H), 2.87-2.94 (m, 1 H), 3.48-3.55 (m, 1 H), 3.73-3.79 (m, 1 H), 3.80-3.96 (m, 1 H), 3.96 (s, 3 H), 4.31-4.35 (m, 1 H), 5.15 (d, J = 11.6 Hz, 1 H), 5.29 (d, J = 11.6 Hz, 1 H), 5.30-5.36 (m, 2 H), 5.32 (br, 1 H), 5.49 (d, J = 7.6 Hz, 1 H), 6.07 (d, J = 8.4 Hz, 1 H), 6.55-6.57 (m, 1 H), 6.75 (t, J = 8.0 Hz, 1 H), 6.89-6.93 (m, 1 H), 6.93-6.97 (m, 1 H), 7.24-7.28 (m, 1 H), 7.33-7.43 (m, 6 H), 7.65-7.67 (m, 2 H), 7.72-7.74 (m, 2 H), 7.75-7.78 (m, 2 H), 7.85-7.89 (m, 2 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 20.05, 29.42, 29.66, 31.15, 35.40, 36.97, 52.39, 53.18, 54.40, 69.79, 72.49, 72.92, 93.04, 99.56, 100.00, 113.03, 113.25, 121.26, 123.13, 123.14, 124.53, 125.04, 127.08, 127.10, 127.71, 127.72, 127.86, 127.88, 128.12, 128.15, 128.35, 128.47, 129.14, 129.15, 129.88, 131.15, 132.27, 133.80, 133.82, 137.68, 141.41, 144.51, 151.69, 153.57, 155.46, 168.06. HRMS: m/z [M + H⁺] calcd for C₄₆H₄₃N₄O₆: 747.3183; found: 747.3141. IR (KBr): 3464, 2951, 2868, 1709, 1606, 1445, 1389, 1189, 719 cm^-¹. [α]_D ^²0 -0.43 (c 1.0, CHC1₃).

11

The crystallographic data of 21a (C₄₆H₄₂N₄O₆) have been deposited with the Cambridge Crystallographic Data Centre; the entry CCDC 776462 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from the Cambridge Crystallo-graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.