Synthesis of Antitumor Benzophenanthridine Alkaloids and Related Compounds

抗肿瘤苯并菲啶生物碱及相关化合物的合成

• 批准号: 61470148
• 负责人: HANAOKA Miyoji
• 金额: $ 3.84万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1986
• 资助国家: 日本
• 起止时间: 1986 至 1987
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-61470148/
• 关键词: Benzophenanthridine Alkaloid; Protoberberine Alkaloid; Antitumor alkaloid Biomimetic Synthesis; Cationic Cyclization; カチオン閉環反応; 立体選択的合成; ベンゾフェナンスリジン; プロトベルベリン; 生合成類似反応; 抗腫瘍性アルカロイド; ファガロニン; ニチジン

1,Regioselective synthesis of 2,3,9,10-oxygenated protoberbering alkaloids was developed starting from readily available benzaldehydes and phenethyl amines.2.2,3,9,10-oxygenated protoberbering were converted to2,3,10,11-oxygenated protoberberines through C_8-C_<8a> bond cleavage followed by photo-cyclization.3.Biomimetic and efficient conversion of berbering to chelerythrine was achieved through regioselective C_6-N bond cleavage,acetalization with thallium trinitrate, and then acidic cyclization.Fagaridine was synthesized from berberine via oxychelerythrine through selective demethylation.4.The above synthetic method was applied to a convevient synthesis of antitumor alkaloids,nitidine and fagaronine.5.This synthetic method was further confirmed tobe a general method for a synthesis of fully aromatized benzophenanthridine alkaloids by a synthesis of oxyterihanine and sanguilutine.6.Chelidonine and chelamine were stereoselectively synthesized from coptisine through cationic cyclization,that established the stereochemistry of chelamine. Similarly,berbering was converted to homochelidonine and chelamidine.7.The present synthesis provides a novel synthesis of both B/C-hexahybro-and fully aromatized benzophenanthridine alkaloids via common intermediates,which gave also sanguinarine and chelerythrine.

1.以苯甲醛和苯乙胺为原料，区域选择性地合成了2，3，9，10-含氧原小檗碱。2.通过C_8-C_2键断裂和光环化反应，将2，3，9，10-含氧原小檗碱转化为2，3，10，11-含氧原<8a>小檗碱。3.通过C_6-C_8键断裂和光环化反应，实现了小檗碱的高效仿生转化。以小檗碱为起始原料，经羟白屈菜红碱选择性脱甲基反应合成了金合欢定碱。4.将上述合成方法应用于抗肿瘤生物碱的快速合成，5.进一步证实了该合成方法是一种通过合成oxyterihanine合成全芳香化苯并菲啶生物碱的通用方法，6.以黄连碱为起始原料，通过阳离子环合反应，立体选择性地合成了白屈菜碱和螯光胺，建立了螯光胺的立体化学结构。7.本合成方法提供了一种新的合成方法，既可以合成B/C-六氢苯并菲啶生物碱，又可以合成全芳香化的苯并菲啶生物碱，还可以合成血根碱和白屈菜红碱。

项目成果

Miyoji Hanaoka: Chem. Pharm. Bull.35. 677-681 (1987)

花冈美代二：化学。

Miyoji Hanaoka: J. Chem. Soc. , Perkin Trans. 1. 35. 195-199 (1987)

花冈美代二：J. Chem。

Shingo Yasuda: "A Novel and Convenient Synthesis of Protoberberine Alkaloids: <plus-minus>-Tetrahydropalmatine,<plus-minus>-Sinactine,<plus-minus>-Canadine,and <plus-minus>-Sted Prot" Tetrahedron Letters. 28. 2399-2402 (1987)

Shingo Yasuda：“一种新颖且方便的原小檗碱生物碱合成：<正负>-四氢延胡索乙素、<正负>-Sinactine、<正负>-Canadine 和 <正负>-Sted Prot”四面体字母。

Miyoji Hanaoka: Heterocycles. 26. 1499-1501 (1987)

花冈美代二：杂环。

Miyoji Hanaoka: "Chemical Transformation of Protoberberines. Part 10.A Novel Synthesis of Sanguilutine and Dihydrosanguilutine,Fully Aromatised 2,3,7,8,10-Pentaoxygenated Benzo[c]phenanthridine Alkaloids" J.Chem.Soc.,Perkin Trans.1. 677-681 (1987)

Miyoji Hanaoka：“原小檗碱的化学转化。第 10 部分。完全芳香化的 2,3,7,8,10-五氧化苯并[c]菲啶生物碱的血桂碱和二氢血桂碱的新合成”J.Chem.Soc.，Perkin Trans。