Synthesis of Antitumor Benzophenanthridine Alkaloids and Related Compounds

1、以苯甲醛和苯乙胺为起始原料，进行了区域选择性合成2,3,9,10-氧合原黄檗生物碱的研究，通过C_8-C_<8a>键裂解和光循环作用，将2,3,9,10-氧合原黄檗转化为2,3,10,11-氧合原黄檗碱。通过区域选择性C_6-N键裂解，与三硝酸铊缩醛化，再进行酸性环化，实现了黄柏素向车车菊啉的仿生高效转化。以小檗碱为原料，经氧切赤藓碱选择性去甲基化，合成Fagaridine。将上述合成方法应用于抗肿瘤生物碱、尼替丁和fagaronine的简便合成。进一步证实了该合成方法是由氧基苯胺和血嘧啶合成完全芳构化苯并苯胺生物碱的通用方法。以黄柏碱为原料，通过阳离子环化，立体选择性地合成了Chelidonine和chelamine，确立了Chelidonine的立体化学性质。同样地，柏柏素被转化为高chelidonine和chelamidine。本合成提供了一种通过常见中间体合成B/ c -六羟基和完全芳构化的苯并苯胺生物碱的新方法，它还得到了血碱和车腥草碱。

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.