| Summary: | 博士 === 國立清華大學 === 化學系 === 91 === 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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