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Synlett 2011(7): 907-910  
DOI: 10.1055/s-0030-1259705
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

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;
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Publication History

Received 12 October 2010
Publication Date:
08 March 2011 (online)

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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

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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).

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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.