莲子心生物碱的研究——Ⅳ.莲心碱的全合成

本文报导了莲心碱(Ⅰ)全合成的研究。(1)合成了1-(3′-溴-4′-苄氧基)苄基-2-甲基-6,7-二甲氧基-1,2,3,4-四氢异喹啉(Ⅷ)和1-(4′-苄氧基)苄基-2-甲基-6-甲氧基7-羟基-1,2,3,4-四氢异喹啉(XV).(2)1-(3′-溴-4′-苄氧基)苄基-6,7-二甲氧基-1,2,3,4-四氢异喹啉(Ⅵ)和1-(4′-苄氧基)苄基-6-甲氧基-7-乙酰氧基-1,2,3,4-四氢异喹啉(ⅩⅢ)借d-和1-DPT-酒石酸各自拆分为其对映体。D-(-)-Ⅵ和L-(+)-Ⅵ以甲酸和甲醛甲基化分别生成D-(-)-Ⅷ和L-(+)-Ⅷ。D-(+)-;ⅩⅢ和L-(-)-ⅩⅢ经N-甲基化后再进行水解卽得D-(-)-ⅩⅤ和L-(+)+ⅩⅤ。(3)D-(-)-Ⅷ和D-(-)-ⅩⅤ在吡啶中有铜粉和碳酸钾存在下进行Ullmann反应,反应物经氧化鋁柱层析可分得一油状物,此油状物经盐酸水解得黄色无定形固体,后者与过氯酸生成过氯酸盐结晶,其理化性质均与天然莲心碱过氯酸盐相同。(±)-Ⅷ和(±)-ⅩⅤ在相似的条件下缩合则生成(±)-莲心碱。

Studies on the Alkaloids of Embryo Loti,Nelumbo nucifera Geartn.——Ⅳ.Total Synthesis of Liensinine

In the present paper, the total synthesis of liensinine, an alkaloid of embryo loti,Nelumbo nucifera Geartn., was described. 1-(3'-Bromo-4'-benzyloxy)benzy1-2-methyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (Ⅷ) and 1-(4'-benzyloxy)benzyl-2-methyl-6-methoxy-7-hydroxy-1,2,3,4-tetrahydroisoquinoline (ⅩⅤ),the two key intermediates,have firstly been synthesized. N-β-(3,4-dimethoxy)phenylethyl amine was condensed with 3-bromo-4-benzyloxy-phenylacetic acid to give the corresponding amide(Ⅳ).Amide (Ⅸ) was converted to the acetyl derivative(Ⅹ). By the Bischler-Nipierlski reaction,compounds(Ⅳ)and(Ⅹ)underwent cyclodehydration to give the corresponding 3,4-dihydroisoquinoline derivatives(Ⅴ)and(Ⅺ).Reduction of the latters with potassium borohydride or sodium borohydride afforded 1- (3'-bromo-4'-benzyloxy) benzyl-6,7-di-methoxy-1,2,3,4-tetrahydroisoquinoline(Ⅵ) and 1-(4'-benzyloxy)benzyl-6-methoxy-7- acetoxy-1,2,3,4-tetrahydroisoquinoline (ⅩⅢ), which were then N-methylated to give Ⅷ and ⅪⅤ respectively.Compound ⅪⅤ was hydrolyzed to afford at last ⅩⅤ. Compound Ⅷ and ⅩⅤ were also prepared by reducing the methiodides Ⅶ and Ⅻ obtained by treatment of compound Ⅴ and Ⅺ with methyl iodide. Secondly the compounds Ⅵ and Ⅷ were resolved into their optical antipodes with satisfactory yield with the aid of (+)-and(-)-DPT-tartaric acid.After N-methyla-tion both D-(-)-Ⅵ and L-(+)-Ⅵ afforded oily D-(-)-Ⅷ and L-(+)-Ⅷ characterized as their crystalline oxalates.D-(+)-ⅩⅢ and L-(-)-ⅩⅢ were methylated and followed by alkaline hydrolysis to give D-(-)-ⅩⅤ and L-(+)-ⅩⅤ respectively. Finally, while D-(-)-Ⅷ and D-(-)-ⅩⅤ were subjected to Ullmann reaction in pyridine in the presence of copper powder and potassium carbonate, there was obtained an oily substance by employing chromatography on alumina. The oily substance was then hydrolyzed to a yellowish amorphorus solid which was converted to crystalline perchlorate identical with natural liensinine perchlorate in all respects.(±)-Liensinine was also synthesized by the condensation of (±)-Ⅷ and (±)-XV in the same condition.