SAITO Naoki Meiji College of Pharmacy, Organic Chemistry, Research Associate, 薬化学教室, 助手 (80142545)
NAKAHARA Akinori Meiji College of Pharmacy, Organic Chemistry, Assistant Professor, 薬化学教室, 講師 (60180337)
KITAHARA Yoshiyasu Meiji College of Pharmacy, Organic Chemistry, Associate Professor, 薬化学教室, 助教授 (70114460)
|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1992 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1991 : ¥1,500,000 (Direct Cost : ¥1,500,000)
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.