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.