P-66 ラジカルカスケードを用いる多環性アルカロイドの全合成(ポスター発表の部)
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概要
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1. Total Synthesis of Stemonamides Stemonamide (1), stemonamine (2), isostemonamide (3), and isostemonamine (4) were isolated from the roots of Stemona japonica, which have been used as Chinese and Japanese folk medicine. Herein, the total synthesis of stemonamide and related alkaloids based on the radical cascade as a key step is described. Radical precursor 6 was readily prepared from 1,2-cyclopentanedione 5. Treatment of 6 with Bu_3SnH/ACN (1,1-azobiscyclohexanecarbonitrile) caused radical cascade involving 7-endo-trig/5-endo-trig cyclization to afford the mixture of tricyclic compounds 7 and 8 (1:1). The mixture of tricyclic compounds 7 and 8 was converted to α,β-nusaturated ketones 9 as the by aldol condensation with benzaldehyde. Addition of lithium ethyl propiolate to α,β-nusaturated ketones 9 afforded compounds 10 and 11 in 50% and 48% yields, respectively. Synthesis of stemonamide (1) and isostemonamide (3) was accomplished by elaboration of compounds 10 and 11 including construction of methyl tetronate moiety, oxidative cleavage of olefin, and introductions of the methyl group and double bond, respectively. Stemonamine (2) and isostemonamine (4) were synthesized from stemonamide (1) and isostemonamide (3) by selective reduction of lactam via thioamidation. 2. Total Synthesis of (-)-Cephalotaxine Cephalotaxine (20), which was isolated from Cephalotaxus harringtonia, has attracted much attention from many chemists due to a combination of its fascinating pentacyclic structure and the antileukemic activity of its ester derivatives such as harringtonine (21) and homoharringtonine (22). Herein, a very short synthesis of (-)-cephalotaxine using the same radical cascade strategy is described. Radical Precursor 30 was readily prepared form known compounds 28 and 29. Treatment of 30 with Bu_3SnH/ACN caused radical cascade involving 7-endo-trig/5-endo-trig cyclization to afford a pentacyclic compound 31. After the removal of silyl groups of compound 31, the resulted diol 32 was oxidized to afford diketone 33. Synthesis of (-)-cephalotaxine 20 was accomplished by selective O-methylation of diketone 33 followed by reduction of two carbonyl groups.
- 2008-09-01