Abstract
摘 要 本論文的第一部分敘述a-碘基烯酮的製備，並利用a-碘基烯酮合成許多天然物所共有的骨架-—六氫苯駢-3-伕喃酮123。在a-碘基烯酮的製備方面，我們以環烯酮為起始物，利用疊氮三甲基矽烷先行與烯酮反應二個小時，以形成有利碘化的中間體b-疊氮三甲矽基烯醇醚100；而後加入碘的沘啶和二氯甲烷溶液，經過碘化和消去反應後可生成a-碘基烯酮59, 73, 103, 105, 106, 107, 108, 109和110，此流程於當起始物環烯酮的b-位置有長大的取代基時亦能有不錯的碘化產率。在六氫苯駢-3-伕喃酮123的合成方面，我們以a-碘基烯酮59為起始物，歷經Luche還原反應、醚類形成反應和陰離子醯化反應後可得到產物123，其中進行陰離子醯化反應時加入氯化三甲基矽烷可充分抑制副反應的發生而使得產率提高至72%。 本論文的第二部分乃延續第一部分陰離子醯化反應的成果，利用此流程來合成天然物avermectins南半邊之六氫苯駢伕喃的片段76。我們以甲基環己烯酮82為起始物，經雙羥基化、保護、烯酮形成反應和碘化反應可生成a-碘基烯酮80，80經Luche還原反應、醚類形成反應和醯胺生成反應可得到Weinreb*s醯胺92，92經陰離子醯化反應可得到環化的烯酮78。78經有機銅1,4-加成反應、去保護、乙醯化和脫水反應後可得到101，惟101進行七號碳的氧化時產率仍不理想，需另覓氧化條件。由起始物82合成至101共使用了十三個步驟，總產率8.6%。Abstract The thesis consists of two parts. Part onedescribes the direct preparation of a-iodoenones and thesynthesis of hexahydrobenzo-3-furanone 123, the common structureof many natural products. Treatment of a b-substitutedcycloalkenone with azidotrimethylsilane and a mixture of iodine/pyridine in dichloromethane afforded the corresponding b-substituted a-iodocycloalkenone. Conjugate addition ofazidotrimethylsilane to cycloalkenone 101 gave an intermediateb-azido trimethylsilyl enol ether 100, which on subsequentiodination and elimination of hydrazoic acid afforded a-iodocycloalkenone 59, 73, 103, 105, 106, 107, 108, 109 and 110.Hexahydrobenzo-3-furanone 123 was synthesized from a-iodoenone59 via Luche reduction, etherification, metal-halogen exchangeand anionic acylation. The addition of chlorotrimethylsilane inanionic acylation reaction trapped the resulting oxyanion andinhibited side reactions. Part two describes theapplication of anionic acylation approach for the synthesis ofhexahydrobenzofuran subunit of avermectins 76.3-Methylcyclohexenone 82 was converted to a-iodoenone 80 viadihydroxylation, protection, enone formation and iodination.Luche reduction of 80 followed by etherification and amideformation gave tethered Weinreb*s amide 92. Metallation andanionic acylation of 92 by n-butyllithium gave cyclized enone78. Organocuprate 1,4-addition of 78 followed by deprotection,acetylation and dehydration afforded 101. But oxidation in C7of 101 was not satisfactory yet. This 13-step conversion of 82to 101 proceeded in 8.6% overall yield.