57(P24) オルト-メタル化を経るイソキノリンアルカロイドの合成(ポスター発表の部)

• 折登 一彦

  北大院工

• 徳橋 隆志

  北大院工

• 堀端 顕議

  北大院工

• 上林 了

  北大院工

• 宮澤 守

  北大院工

• 徳田 昌生

  北大院工

書誌事項

タイトル別名

• 57(P24) SYNTHESIS OF ISOQUINOLINE ALKALOIDS VIA ORTHO-METALLATION

抄録

Benzolactone and benzolactam units are found in some groups of biologically active, naturally occurring heterocyclic compounds. We have developed a new method for the synthesis of such heterocycles, based on carboxylation or carbonylation via aromatic metallations induced by halogen-metal exchanges and ortho-metallations, leading to isoquinoline alkaloids. Stereoselective hydride reduction of 1-(2-bromobenzoyl)-3,4-dihydroisoquinolines 1, followed by carboxylation of the resultant erythro- and threo-amino alcohols 2 and 2' with CO_2 gas via a halogen-lithium exchange with BuLi, gave the corresponding benzolactones 3. Palladium-catalyzed carbonylation [Pd(OAc)_2-PPh_3/K_2CO_3/CO/boiling toluene] of 2 and 2' was found to be accelerated by an addition of Me_3SiCl, and resulted in the almost quantitative formation of erythro- and threo-phthalideisoquinoline alkaloids 3 and 3' after 20h. Treatment of erythro-amino alcohols 2 with K_2CO_3 in boiling DMF gave indolo[2,1-a]isoquinolines 6 in good yields. 1-(2-Bromobenzyl)-1,2,3,4-tetrahydroisoquinolines 11 were also subjected to a similar palladium-catalyzed carbonylation. The products, benzolactams 8, were subsequently treated with LiAlH_4 to give the corresponding protoberberine alkaloids 12 in good yields. When the carbamate (7) of 11 was treated with t-BuLi at room temperature, 8-oxoberbine (9) having t-Bu group at its 9 position in place of an alkoxy group was obtained in a good yield. A similar treatment with n-BuLi gave 8-butylidene derivative (10) of 8. It was found that palladium(0)-catalyzed carbonylation of 1-(3,4-methylene-dioxybenzyl)-1,2,3,4-tetrahydroisoquinoline 13 also gave 8-oxoberbine 8' with a 9,10-methylenedioxy group. In contrast, 3,4-dimethoxy derivative 14 gave only 10,11-dimethoxy-8-oxoberbine 15 by carbonylation with a stoichiometric amount of Pd(OAc)_2. Benzophenanthridine alkaloids, oxysanguinarine 24 and oxyavicine 25, were synthesized by similar carbonylations of naphthyl amines 20 and 22.

収録刊行物

• 天然有機化合物討論会講演要旨集

  天然有機化合物討論会講演要旨集 39 (0), 337-342, 1997

  天然有機化合物討論会実行委員会

詳細情報

• CRID: 1390282681055526144
• NII論文ID: 110006679551
• DOI: 10.24496/tennenyuki.39.0_337
• ISSN: 24331856
• 本文言語コード: ja
• データソース種別:
  • JaLC
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可