Abstract
以(s)-dihydrocarvone 124為起始物, 依照Takazawa的方法, 在其烯酮官能基的γ位置引入一個碳單元, 接著進行Rubottom反應可得到α三甲基矽氧基酮 126, 然後在酸性催化下即可得到重要中間體架橋雙環烯酮127,烯酮 127進行1,4-加成反應後, 以氯化三甲基矽烷捕捉生成的烯醇陰離子即順利得到矽烯醇醚 129, 再以本實驗室發展的方法, 加入碘化鈉及間－氯過氧苯甲酸即得α－碘基酮 130, 130 進行自由基環化反應, 以慢慢加入三丁基氫化錫的技巧可得烯酮 131, 此時已具備了目標物所有的骨架原子, 烯酮 131進行質子加成去矽基反應得 132, 接著依照Grieco的方法, 加入乙醚合三氟化硼及間－氯過氧苯甲酸即可將內縮醛氧化成內酯156,內酯 156在進行氫硼化反應時也還原了酮基, 最後得到的產物是雙醇 162,選擇性將一級醇作成磺酸酯, 再以疊氮化鈉取代便得疊氮化物164, 164 的二級醇以Jones 試劑氧化後可得酮 165, 165 進行Staudinger反應可得環亞胺, 在一鍋法的條件下, 加入還原劑還原所得的亞胺便可得到二級胺 168, 二級胺 168不須進一步純化直接進行氮的甲基化即完成石斛鹼 1 的全合成。 (±)-pinguisone 的全合成工作方面, 目前已完成模型研究(model study), 以苯環代替furane環部份, 對2-甲基2-環戊烯酮進行1,4-加成反應－碘化反應－自由基環化反應即可得到環化加成產物, 接著進行質子加成去矽基反應也可順利達成, 我們也已經成功製備出2,3,4-三甲基2-環戊烯酮及furane化物, 後續的研究工作正在進行中。(s)-Dihydrocarvone 124 was treated sequentially with MeMgCl,FeCl3, TMSCl and then a mixture of trimethyl orthoformate andboron trifluoride etherate to give acetal 125. Reaction of 125with LDA and TMSCl generated the corresponding trimethylsilylenol ether, which was treated with m-CPBA to give siloxy-enone127. Cuprous iodide mediated conjugate addition to 127followed by trapping with TMSCl yielded 129. Iodination ofcrude 129 with a mixture of NaI and m-CPBA in THF gave iodoketone 130. The tricyclic ketone 131 was formed when iodoketone 130 was treated with tributyltinhydride and AIBN by theslow addition technique. Removal of the TMS group from 131 bytrifluoroacetic acid gave 132, which was oxidized by m-CBA inthe presence of boron tri- fluoride etherate to give a labileperoxy compound 161. Crude compound 161 was converted to lacton156 upon the addition of DBU. Hydroboration of 156 with boranedimethyl sulfide complex followed by oxidative workup gave diol162. Treatment of 162 with MsCl and triethyl amine gave 163.Reaction of 163 with NaN3 afforded 164. Jones oxidation of 164yielded azido ketone 165. Staudinger reaction of 165 withtriphenylphosphine followed by sodium cyanoborohydridereduction afforded amine 168. The crude amine 168 wasmethylated to give (-)-dendrobine (1).