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The synthesis of (S)-(+)-tylophorine and its seco analogues has been accomplished by using free radical reaction. -N-(2,3,6,7-Tetramethoxyphenanthren-9-ylmethyl)-2-bromomethylpyrrolidine (7) and -N-(2,3,6,7-tetramethoxyphenanthren-9-ylcarbonyl)-2-bromomethylpyrrolidine (9) have been obtained for the first time in three and two linear steps from 2,3,6,7-tetramethoxyphenanthrene-9-carboxylic acid (4), respectively. When bromide 7 was subjected to the action of tri-n-butyltin hydride and catalytic amount of azobisisobutyronitrile in acetonitrile at reflux, only a new structural N-((2,3,6,7-tetramethoxyphenanthren-9-yl)methyl)piperidine (2) was obtained in excellent yield, without expected (+)- ty- lophorine. As an alternative route, when bromide 9 was treated with azobisisobutyronitrile and tri-n-butyltin hydride in toluene at reflux, tylophorin-9-one (10) was provided in 33.6% yield. At the same time, a new structural (+)-N-((2,3,6,7-tetramethoxyphenanthren-9-yl)carbonyl)-2-methylpyrrolidine (11) was afforded as the main product in 65% yield. Notably, azobisisobutyronitrile plays dual roles in this reaction, and the possible mechanism has been described. Compounds 10 and 11 were reduced by lithium aluminum hydride to give (+)-tylophorine and (+)-N-((2,3,6,7-tetramethoxyphenanthren-9-yl) methyl)-2-methylpyrrolidine (3), respectively.
The synthesis of (S) - (+) - tylophorine and its seco analogues has been accomplished by using free radical reaction. N- (2,3,6,7-Tetramethoxyphenanthren-9-ylmethyl) -2-bromomethylpyrrolidine and N- (2,3,6,7-tetramethoxyphenanthren-9-ylcarbonyl) -2-bromomethylpyrrolidine (9) have been obtained for the first time in three and two linear steps from 2,3,6,7-tetramethoxyphenanthrene- 9-carboxylic acid (4), respectively. When bromide 7 was subjected to the action of tri-n-butyltin hydride and catalytic amount of azobisisobutyronitrile in acetonitrile at reflux, only a new structural N - ((2,3,6,7 -tetramethoxyphenanthren-9-yl) methyl) piperidine (2) was obtained in excellent yield, without expected (+) - ty- lophorine. When amber 9 was treated with azobisisobutyronitrile and tri-n-butyltin hydride in toluene At the same time, a new structural (+) - N - ((2,3,6,7-tetramethoxyphenanthren-9-yl) carbonyl) -2-methylpyrroli Notably, azobisisobutyronitrile plays dual roles in this reaction, and the possible mechanism has been described. Compounds 10 and 11 were reduced by lithium aluminum hydride to give (+) - tylophorine and (+) - N - ((2,3,6,7-tetramethoxyphenanthren-9-yl) methyl) -2-methylpyrrolidine