New Synthesis of a Pyrroloquinoline Skeleton, the Martinelline Core, Using a Tandem Michael-Aldol Strategy

Osamu Hara; Kazuhiko Sugimoto; Kazuishi Makino; Yasumasa Hamada

doi:10.1055/s-2004-829085

LETTER

New Synthesis of a Pyrroloquinoline Skeleton, the Martinelline Core, Using a Tandem Michael-Aldol Strategy

Osamu Hara^b, Kazuhiko Sugimoto^a, Kazuishi Makino^a, Yasumasa Hamada*^a
^a Graduate School of Pharmaceutical Sciences, Chiba University, Yayoi-cho, Inage-ku, Chiba, 263-8522, Japan
Fax: +81(43)2902987; e-Mail: hamada@p.chiba-u.ac.jp.;
^b Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 460-8503, Japan

Abstract

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Abstract

The pyrroloquinoline moiety of Martinelline, a naturally occurring bradykinin receptor antagonist, has been synthesized from 1,2-dihydroquinoline which was prepared by using a tandem Michael-aldol reaction as a key step.

Key words

aldol reactions - Michael reactions - cyclizations - pyrroloquinoline - tandem reactions

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References

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7 Compound 27: amorphous powder. IR (KBr): 3389, 2979, 1700, 1685, 1559, 1458 cm^-1. ¹H NMR (CDCl₃, 55 °C): δ = 1.09-1.19 (m, 1 H), 1.23-1.43 (m, 22 H), 1.62-1.75 (m, 3 H), 2.37 (s, 3 H), 3.08-3.22 (m, 4 H), 4.51-4.55 (m, 2 H), 6.45 (m, 1 H), 6.54 (d, J = 2.7 Hz, 1 H), 6.73 (dd, J = 8.5, 2.4 Hz, 1 H), 7.19 (d, J = 8.1 Hz, 2 H), 7.34 (d, J = 8.5 Hz, 1 H), 7.48 (d, J = 8.1 Hz, 2 H). ¹³C NMR (CDCl₃, 55 °C): δ = 21.4, 27.1, 28.5, 54.1, 80.0, 112.9, 114.9, 125.3, 126.9, 129.9, 130.4, 136.4, 155.7, 156.3. HRMS-FAB: m/z calcd for C₃₁H₄₃O₇N₃S: 601.2822 [M⁺ + 1]. Found: 601.2792 [M⁺ + 1]