Total Synthesis of (-)-Neoechinulin A

Toshiaki Aoki; Shinji Kamisuki; Masaaki Kimoto; Kensuke Ohnishi; Yoichi Takakusagi; Kouji Kuramochi; Yoshifumi Takeda; Atsuo Nakazaki; Kenji Kuroiwa; Takashi Ohuchi; Fumio Sugawara; Takao Arai; Susumu Kobayashi

doi:10.1055/s-2006-933113

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Synlett 2006(5): 0677-0680
DOI: 10.1055/s-2006-933113

LETTER

Total Synthesis of (-)-Neoechinulin A

Toshiaki Aoki^a,b, Shinji Kamisuki^c, Masaaki Kimoto^c, Kensuke Ohnishi^a,b, Yoichi Takakusagi^a,b, Kouji Kuramochi^c, Yoshifumi Takeda^a,b, Atsuo Nakazaki^a, Kenji Kuroiwa^c, Takashi Ohuchi^c, Fumio Sugawara^a,c, Takao Arai^c, Susumu Kobayashi*^a,b
^a Faculty of Pharmaceutical Sciences, Tokyo University of Science (RIKADAI), 2641 Yamazaki, Noda, Chiba 278-8510, Japan
Fax: +81(4)71213671; e-Mail: kobayash@rs.noda.tus.ac.jp;
^b Frontier Research Center for Genome and Drug Discovery, Tokyo University of Science (RIKADAI), 2641 Yamazaki, Noda, Chiba 278-8510, Japan
^c Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science (RIKADAI), 2641 Yamazaki, Noda, Chiba 278-8510, Japan

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Publication History

Received 10 December 2005
Publication Date:
09 March 2006 (online)

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Abstract

A total synthesis of neoechinulin A was accomplished with high enantiomeric excess. Our total synthesis of neoechinulin A established the absolute configuration of natural neoechinulin A. The synthetic route features aldol condensation of a 3-formyl indole derivative and intramolecular cyclization.

Key words

natural product - total synthesis - alkaloid - aldol reaction - cyclization

References and Notes

1a Itokawa H. Akita Y. Yamazaki M. Yakugaku Zasshi 1973, 93: 1251

Crossref Google Scholar
1b Dossena A. Marchelli R. Pochini A. J. Chem. Soc., Chem. Commun. 1974, 771

Crossref Google Scholar
1c Nagasawa H. Isogai A. Ikeda K. Sato S. Murakoshi S. Suzuki A. Tamura S. Agric. Biol. Chem. 1975, 39: 1901

Crossref Google Scholar
1d Marchelli R. Dossena A. Pochini A. Dradi E. J. Chem. Soc., Perkin Trans. 1 1977, 713

Crossref Google Scholar
2 Yagi R. Doi K. Biosci. Biotechnol. Biochem. 1999, 63: 932

Crossref PubMed Google Scholar
3 Li Y. Li X. Kim S.-K. Kang JS. Choi HD. Rho JR. Son BW. Chem. Pharm. Bull. 2004, 52: 375

Crossref PubMed Google Scholar
4 Maruyama K. Ohushi T. Yoshida K. Shibata Y. Sugawara F. Arai T. J. Biochem. 2004, 136: 81

Crossref PubMed Google Scholar
5 Marchelli R. Dossena A. Casnati G. J. Chem. Soc., Chem. Commun. 1975, 779

Crossref Google Scholar
6 Oikawa Y. Yoshikawa T. Yonemitsu O. Tennen Yuki Kagobutsu Toronkai Koen Yoshishu, 21st. 1978, 22

Google Scholar
7 Nakatsuka S. Miyazaki H. Goto T. Tetrahedron Lett. 1980, 21: 2817

Crossref Google Scholar
8 Cledera P. Avendaño C. Menéndez JC. Tetrahedron 1998, 54: 12349

Crossref Google Scholar
9a Tatsuta K. Mukai H. Mitsumoto K. J. Antibiot. 2001, 54: 105

Crossref Google Scholar
9b Schkeryantz JM. Woo JCG. Danishefsky SJ. J. Am. Chem. Soc. 1995, 117: 7025

Crossref Google Scholar
10 Sanz-Cervera JF. Glinka T. Williams RM. Tetrahedron 1993, 49: 8471

Crossref Google Scholar
11 Vilsmeier A. Haack A. Ber. 1927, 60: 119

Crossref Google Scholar
12a Smith GG. Baum R. J. Org. Chem. 1987, 52: 2248

Crossref Google Scholar
12b Hayashi Y. Orikasa S. Tanaka K. Kanoh K. Kiso Y. J. Org. Chem. 2000, 65: 8402

Crossref Google Scholar
13 Beugelmans R. Neuville L. Bois-Choussy M. Chastanet J. Zhu J. Tetrahedron Lett. 1995, 36: 3129

Crossref Google Scholar
14 Zimmerman HE. Ahramjian L. J. Am. Chem. Soc. 1959, 81: 2086

Crossref Google Scholar

15

All new compounds were fully characterized on the basis of spectral data (IR, ¹H NMR, ¹³C NMR, and HRMS).
Compound 4: yellow oil, [α]_D ²⁵ -66.8 (c 0.62, MeOH). IR (neat): 3465, 1690, 1630, 1460 cm^-1. ¹H NMR (600 MHz, CDCl₃): δ = 1.55 (s, 6 H), 1.59 (d, J = 7.0 Hz, 3 H), 2.64 (s, 3 H), 3.40 (s, 3 H), 5.06 (d, J = 17.5 Hz, 1 H), 5.12 (q, J = 7.0 Hz, 1 H), 5.14 (d, J = 10.6 Hz, 1 H), 5.52 (s, 2 H), 6.19 (dd, J = 10.6, 17.5 Hz, 1 H), 7.16-7.19 (m, 3 H), 7.44 (d, J = 8.3 Hz, 1 H), 7.47 (s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 20.0, 27.0, 29.75, 29.81, 40.7, 52.8, 55.7, 75.2, 105.4, 110.6, 112.3, 117.6, 118.6, 121.7, 123.3, 124.9, 125.5, 138.1, 146.6, 166.3, 172.0. ESI-MS: m/z calcd for C₂₃H₂₇N₃O₄Na [M + Na]⁺: 432.1893; found: 432.1905.
Compound 5: white solid, mp 180-182.5 °C (EtOAc-hexane); [α]_D ²⁶ -15.5 (c 0.61 MeOH). IR (KBr): 3200, 3060, 2970, 2930, 2870, 1670, 1635 cm^-1. ¹H NMR (600 MHz, CDCl₃): δ = 1.58 (d, J = 7.0 Hz, 3 H), 1.59 (s, 6 H), 3.39 (s, 3 H), 4.28 (dq, J = 1.6, 7.0 Hz 1 H), 5.05 (d, J = 17.5 Hz, 1 H), 5.12 (d, J = 10.6 Hz, 1 H), 5.50 (s, 2 H), 6.18 (dd, J = 10.6, 17.5 Hz, 1 H), 6.68 (br, 1 H), 7.16 (t, J = 7.2 Hz, 1 H), 7.21-7.25 (m, 2 H), 7.32 (br, 1 H), 7.42 (d, J = 7.2 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 20.8, 29.7, 40.5, 51.6, 55.6, 75.1, 105.1, 110.3, 112.1, 113.1, 118.9, 121.3, 123.1, 125.2, 125.4, 138.0, 143.2, 146.8, 159.5, 165.6. ESI-MS: m/z calcd for C₂₁H₂₅N₃O₃Na [M + Na]⁺: 390.1788; found: 390.1794.
Compound 10: yellow amorphous; [α]_D ²⁵ +20.6 (c 1.85 MeOH). IR (KBr): 3320, 3055, 2975, 2940, 1710, 1630, 1505, 1440, 1375 cm^-1. ¹H NMR (600 MHz, CDCl₃): δ = 1.13 (d, J = 7.0 Hz, 3 H), 1.35 (t, J = 7.1 Hz, 3 H), 1.57 (s, 6 H), 4.32 (dq, J = 1.4, 7.1 Hz, 2 H), 4.46 (m, 2 H), 5.18-5.28 (m, 4 H), 5.86 (m, 1 H), 6.10 (dd, J = 10.6, 6.7 Hz, 1 H), 7.07 (t, J = 7.2 Hz, 1 H), 7.14 (t, J = 7.2 Hz, 1 H), 7.24 (d, J = 7.2 Hz, 1 H), 7.31 (d, J = 7.2 Hz, 1 H), 7.33 (br, 1 H), 7.72 (s, 1 H), 8.26 (br, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 14.2, 18.3, 27.46, 27.52, 39.2, 50.4, 61.4, 65.7, 106.3, 111.1, 113.1, 117.7, 120.2, 120.4, 122.0, 122.5, 126.1, 126.2, 132.5, 134.1, 144.3, 144.5, 155.5, 164.8, 170.0. ESI-MS: m/z calcd for C₂₅H₃₁N₃O₅Na [M + Na]⁺: 476.2155; found: 476.2173.
Neoechinulin A: white needle crystal, mp 272-275 °C; [α]_D ²³ -55 (c 0.59 MeOH; 93% ee). IR (KBr): 3300, 3060, 2970, 2925, 1680, 1630 cm^-1. ¹H NMR (600 MHz, DMSO-d ₆): δ = 1.37 (d, J = 6.9 Hz, 3 H), 1.47 (s, 6 H), 4.17 (dq, J = 6.9, 1.7 Hz, 1 H), 5.02 (d, J = 17.8 Hz, 1 H), 5.05 (d, J = 11.0 Hz, 1 H), 6.07 (dd, J = 11.0, 17.8 Hz, 1 H), 6.88 (s, 1 H), 7.00 (t, J = 7.4 Hz, 1 H), 7.08 (t, J = 7.4 Hz, 1 H), 7.19 (d, J = 7.4 Hz, 1 H), 7.41 (d, J = 7.4 Hz, 1 H), 8.37 (s, 1 H), 8.77 (s, 1 H), 11.07 (s, 1 H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 19.8, 27.7, 39.2, 50.7, 103.6, 110.3, 110.7, 111.8, 119.1, 119.5, 120.9, 125.1, 126.2, 135.3, 144.1, 145.3, 160.1, 166.6. ESI-MS: m/z calcd for C₁₉H₂₁N₃O₂Na [M + Na]⁺: 346.1525; found: 346.1531.