Synthetic Studies on Biological Active Marine Natural Products Possessing Iminoquinolinequinone Structure

在过去的十年里，从海洋生物和植物中分离出了多种多环芳香生物碱，如苯并咪啶、胱氨酸二异氰酸酯A-I、双胺A、美尼定、11-羟基海藻二胺(1)、鸟钩藤碱A(2)和真核生物碱1(3a)、2(3b)和3(3c)。本项目的目的是为具有亚氨基喹诺酮结构的生物碱开发一条通用的合成路线。1-3(3a-c)的合成：(6-甲氧基)1，4-萘醌和(2-甲氧基)2-丁烯基二甲基肼经Diels-Alder杂化反应得到4a-c。用DMF二乙缩醛处理4a-c，然后在冰醋酸中处理氯化铵，得到3a-c。葛根素A(2)的合成：6-甲氧基苯并-4，7-二酮和2-氨基苯乙酮在氯化铈存在下在甲醇中反应得到5。5用DMF二乙缩醛处理，然后在冰醋酸中用氯化铵反应得到2.3。以4-甲氧基-5，8-喹啉二酮和2-氨基苯乙酮为原料合成11-羟基海藻双菌素(1)：11-甲氧基海鞘双菌素(6)，再用三溴化硼处理得到1，4，6-甲氧基-5，8-喹啉二酮和2-氨基-5-甲氧基苯乙酮合成的新蒜素乙酸酯(7)的结构测定结果与新蒜氨酸乙酸酯的结构一致。因此，我们确定了新决明酸乙酸酯的结构为8，即3-乙酰氧基阿司匹林。降冰片灵(9)的合成：以4-氨基-3-甲氧基苯甲酸甲酯为原料，合成了一种用于制备半胱氨酸等的中间体。现在，我们正在研究半胱氨酸A和B的合成，以及双胺A的合成。

During the past ten years a variety of polycyclic aromatic alkaloids have been isolated from marine organisms and plants ; e.g.amphimedine, cystodytins A-I, diplamine A, meridine, 11-hydroxyascididemin (1), kuanoniamine A (2), and eupomatidines 1 (3a), 2(3b) and 3 (3c). The purpose of this project is to develop a common synthetic route for the alkaloids possessing iminoquinolinequinone structure.1. Synthesis of eupomatidines 1-3 (3a-c)(isolated from a tree) : The hetero Diels-Alder reaction of (6-methoxy-) 1, 4-naphthoquinone and (2-methoxy-)2-butenal dimethylhydrazine followed by dehydrogenation gave 4a-c. Treatment of 4a-c with DMF diethyl acetal followed by ammonium chloride in acetic acid furnished 3a-c.2. Synthesis of kuanoniamine A (2) : The reaction of 6-methoxybenzothiazole-4, 7-dione and 2-aminoacetophenone in the presence of cerium (III) chloride in methanol gave 5. Treatment of 5 with DMF diethyl acetal followed by ammonium chloride in acetic acid furnished 2.3. Syntheses of 11-hydroxyascididemin (1) : 11-Methoxyascididemin (6) prepared from 4-methoxy-5, 8-quino-linedione and 2-aminoacetophenone by the similar method, was treated with boron tribromide to afford 1.4.Structure determination of neocalliactine acetate, derivative of calliactine : 3-Methoxyascididemin (7) prepared from 6-methoxy-5, 8-quinolinedione and 2-amino-5-methoxyacetophenone by the similar method, was treated with hydrobromic acid followed by acetic anhydride in pyridine to afford 8. The spectral data of synthetic 8 were identical with those of neocalliactine acetate. Thus, we determined the structure of neocalliactine acetate to be 8 i.e. 3-acetoxyascididemin.5. Synthesis of norsegoline (9) : Norsegoline (9) a useful intermediate for the preparation of cystodytins etc, was synthesized from methyl 4-amino-3-methoxybenzoate. Now, we are studying the synthesis of cystodytins A and B, and diplamine A via 9.