P-29 Synthetic Studies on Martinellines via Radical Addition-Cyclization-Elimination Reaction as a Key Step

• Miyata Okiko

  Kobe Pharmaceutical University

• Shirai Atsushi

  Kobe Pharmaceutical University

• Yoshino Shintaro

  Kobe Pharmaceutical University

• Nakabayashi Toshiki

  Kobe Pharmaceutical University

• Takeda Yoshifumi

  Kobe Pharmaceutical University

• Naito Takeaki

  Kobe Pharmaceutical University

Bibliographic Information

Other Title

• P-29 ラジカル付加閉環脱離反応を鍵反応とするMartinelline類の合成研究(ポスター発表の部)

Abstract

The martinellines (1a and 1b) have attracted considerable interest since they were isolated from an organic extract of the Martinella iquitosensis root by Witherup in 1995, principally because of antagonist activity to some G-protein coupled receptors such as bradykinin B_1 and B_2, α_1-adrenergic, and muscarinic receptors. In addition, both alkaloids contain pyrroloquinoline ring system, which has not been discovered in natural products so far. We developed a new synthetic route involving the preparation of pyrroloquinoline core via radical addition-cyclization-elimination (RACE) reaction. (1) Radical Addition-Cyclization-Elimination Reaction of Oxime Ethers Carrying Unsatutated Ester Treatment of 5 with Bu_3SnH and AIBN gave pyrroloquiniline 6 as a result of RACE reaction. Similarly, the oxime ether 9 was subjected to RACE reaction to give 10 with an alkyl chain. We found a useful RACE reaction which has provided a novel and efficient method for the construction of the pyrroloquinolines which is key step for synthesis of martinellines. (2) Formal Synthesis of (±)-Martinelline A formal synthesis of (±)-martinelline has been accomplished via two types of radical reactions as the key steps. The cis-pyrroloquinoline 6, prepared from oxime ether 5 by RACE reaction, was converted into 17 having the acetyl group at C8 position via the reduction, Friedel-Crafts reaction, and acylation. The amide 17 was treated with Bu_3SnH and AIBN in the presence of methyl acrylate to give the desired compound 18 as a single diastereomer which was formed via a 1,5-hydrogen atom translocation and subsequent Michael-type radical addition. Finally, the pyrroloquinoline 18 was transformed into the desired alcohol 21 which is a key intermediate for the synthesis of (±)-martinelline. (3) Formal Synthesis of (-)-Martinellic Acid The optically active substrate 28b for RACE reaction was prepared via the coupling reaction of 27b with (S)-5-oxoproline ethyl ester in the presence of Pd_2(dba)_3. RACE reaction of 28b proceeded smoothly to give the dipyrroloquinoline 29b. The chemoselective reduction of (3aR,11bS)-29b having three different types of carbonyl groups followed by acylation of the resulting amine with TFAA gave the desired trifluoroacetamide 32 which has been previously converted into (-)-martinellic acid.

Journal

• Symposium on the Chemistry of Natural Products, symposium papers

  Symposium on the Chemistry of Natural Products, symposium papers 47 (0), 319-324, 2005

  Symposium on the Chemistry of Natural Products Steering Committee

Details

• CRID: 1390282681055413760
• NII Article ID: 110006682565
• DOI: 10.24496/tennenyuki.47.0_319
• ISSN: 24331856
• Text Lang: ja
• Data Source:
  • JaLC
  • CiNii Articles
• Abstract License Flag: Disallowed