P-57 金触媒を用いたアレニルシランの分子内環化反応を鍵とする(-)-Funebrineの全合成(ポスター発表の部)

抄録

(-)-Funebrine (1) is a novel pyrrole alkaloid isolated from fragrant flowers of Quararibea funebris at near Oaxaca, Mexico in 1984. The flowers have been used as a folk medicine for treating various diseases, and have also been used as an additive to chochlate drinds since pre-Columbian times. The structure of 1 was characterized by a 2,5-substituted pyrrole and two aminolactones poseessing three contiguous stereo centers. The datailed biological aactivity of 1 has not been unidentified probably due to insufficient supply of natural product. Only one report on an asymmetric synthesis of (-)-1 has been reported. Our synthetic plan toward the total synthesis of 1 was the use of α-amino γ-butyrolactone 4 as the key inermediate, which could be prepared via the enolate Claisen rearranement of the propargylsilane 5 followed by the novel Au-catalyzed regioselective γ-lactonization of the resulting allenylsilane 6. The Claisen rearrangement of optically active 5 gave desired allenylsilane 6. After screening of Au and other catalysts, [(Ph_3PAu)_3O]BF_4 was found to effectively catalyze the regiospecific γ-lactonizaton of 6 to give vinylsilane-containing γ-butyrolactone 7a. Since subsequent conversion of 7a to 4 was accompanied by a troublesome epimerization at C3, dimethylphenylsilane derivative 11 instead of 6a was employed as the starting material. Both the Claisen rearrangement and Au-catalyzed γ-lactonization proceeded smoothly to furnish the γ-butyrolactone 12 in a highly efficient manner, which, upon 4 step sequence of reactions, gave 4. Condensation of 4 with 1,4-diketone 3a produce the pyrrole-coupled 15. Finally, total synthesis of (-)-funebrine (1) was accomplished by the treatment of 2 with 4 upon heating.