A series of phenanthroindolizidine and phenanthroquinolizidine alkaloids and their (13aS,14S)-14-amino-derivat...
Ziwen Wang~a,Meng Wu~a,Zheng Li~a,Lei Wang~a,Gui fang Han~a,Fazhong Chen~a,Yu xiu Liu~a, Kai liang Wang~b,Ao Zhang ~(*,b),Linghua Meng~c,Qing min Wang~(*,a) a:State Key Laboratory of Elemento-Organic Chemistry,Research Institute of Elemento-Organic Chemistry,Nankai University,Tianjin 300071,People’s Republic of China
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.
