本論文第一部份是敘述(-)-manthine (3)全合成研究。從商業可獲得的D-(-)-quinic acid 67經四步反應可得到具光學活性的起始物烯酮68，接著進行Johnson碘化反應、Luche還原反應、Mitsunobu反應和陰離子環化反應後生成多氫吲哚酮73，之後利用Luche還原反應得醇並轉換成烯炳酯和位置選擇性烷化反應作成75，75經濃鹽酸水解產生雙醇78。一開始我們將雙醇78轉為單一保護化合物84，反轉C3位置之立體化學生成86，經水解、去保護、二甲基化後生成89，但因84反應成86之再現性不佳，造成後續全合成推進之不易，故我們改從雙醇78先製備單一芐基保護產物80，80再作成乙醯基化合物82，經水解、甲基化生成93，接著將化合物93進行去N-對甲苯磺醯基保護得二級胺94，利用Pictet-Spengler環化反應建立5,11-methanomorphanthridine骨架得到95，最後以BF3•OEt2移除芐基並轉為甲基順利完成(-)-manthine (3)全合成。
本論文第二部分是敘述(-)-stenine (2)全合成研究。合成途徑1中，首先以59為起始物，利用Mitsunobu反應製備Weinreb’s amide 61，接著進行anionic cyclization得環化產物62，藉由1,4-加成反應生成68，後經三步官能基轉換反應移除□基保護得71，惟62作成68之產率雖嘗試改善卻仍偏低，最後不得不放棄此路徑。合成途徑2中，我們以77當起始物，同樣經Mitsunobu反應、anionic cyclization得環化產物80，建立天然物六、七環骨架，80進行1,4-加成反應引入C9位置上的乙基得到84，化合物84經X-ray單晶繞射分析實驗確定結構後，接著移除□基、解離acetonide保護後生成87。後續我們計劃先建立內酯環部分，然後在C12引入二個碳支鏈、去N-對甲苯磺醯基保護來建立五圓環部分，期望完成(-)-stenine (2)全合成。

The thesis consists of two chapters. The first chapter describes the total synthesis of (-)-manthine (3). We chose optically pure enone 68 as starting material, which was prepared from commercially available D-(-)-quinic acid 67 in four chemical operations. Iodination of enone 68 followed by Luche reduction, Mitsunobu reaction and anionic cyclization furnished perhydroindole 73 in 48% overall yield. Treatment of 73 with NaBH4 in the presence of CeCl3•7H2O, followed by subsequent esterification with pivaloyl chloride in pyridine gave the allylic pivalate 74. Regioselective alkylation of 74 with 3,4-(methylenedioxy)phenylmagnesium bromide in the presence of 10% CuI afforded 75 in 91%. Hydrolysis of 75 with conc. HCl gave diol 78. Regioselective monobenzylation of diol 78 with benzaldehyde dimethylacetal in the presence of catalyst CSA, followed by reduction with DIBALH formed 80 in 97%. Treatment of 80 with trifluoromethanesulfonic anhydride and pyridine led to inversion of configuration at the carbon atom attached hydroxy moiety to afford unstable triflate 81. Reaction of 81 with cesium acetate and 18-crown-6 in toluene produced acetate 82. Hydrolysis of acetate 82 followed by methylation provided 93. Cleavage of sulfonamide in 93 with sodium naphthalide followed by conventional Pictet-Spengler cyclization afforded 5,11-methanomorphanthridine skeleton 95. Finally removal of benzyl group with BF3•OEt2 and DMS followed by methylation achieved (-)-manthine (3). Thus, the total synthesis of (-)-manthine (3) was completed in 4.6% overall yield from enone 68 in eighteen synthetic operations.
The second chapter presents study of total synthesis of (-)-stenine (2). The key starting material allylic alcohol 78 was synthesized as disclosed in the previous chapter. Mitsunobu reaction of 78 followed by anionic cyclization gave perhydrobenzoazepine 80 in 70%. Treatment of 80 with ethylmagnesium bromide in the presence of CuI, HMPA, TMSCl and Et3N underwent 1,4-addition to produce silylenolether 82 in 79%, followed by hydrolysis with 2 N HCl afforded ketone 84 in 68%. Reduction of carbonyl group was carried out by means of Wolff-Kishner reaction to generate 86 in 52%. Acetonide was hydrolyzed with conc. HCl to achieve diol 87 in 88%. Further efforts have to be made to ultilize the compound 87 for the total synthesis of (-)-stenine (3).

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