中文摘要
本論文報導solidagolactone IV (62) 及V (63) 的全合成。整個策略的關鍵步驟是利用具有面向選擇性的Diels-Alder 環化加成反應來建立順式-十氫□骨架以及所需的立體位向。
如流程十三所示，親二烯化合物 73 可以從烯酮化合物 45 來合成。首先用4-溴-1-丁烯對化合物 45進行烷化，得到化合物 76， 接著用四氫鋁化鋰 (LAH) 還原後，加酸水解，並使其重排得到烯酮化合物 77 。化合物 77 經過三個步驟的轉換 (isoxazole route) 在α位置引進氰基後可得α氰基酮 80 。接著用DDQ進行氧化可得親二烯化合物 73 。
親二烯化合物 73 用碘化鋅催化進行Diels-Alder環化加成反應得化合物 82 ，此化合物可用□化鋰試劑進行還原取代反應 (reductive alkylation) 將氰基轉換為甲基可得化合物 84 ，並保有原先的立體位向。在一溴三甲基矽烷 (TMSBr) 的活化下，用Me2CuLi對 84 進行1,4加成可得高立體選擇性產物 85 ，LAH還原化合物 85 同樣具有高度的立體選擇性而得到化合物 95， 使用MOMCl保護化合物 95 的羥基 (hydroxyl group) ，可使接下來的Wacker反應順利進行而得到甲基酮化合物 100 ，使用dimethyldioxirane 103 試劑可成功地建立α-羥基酮化合物 101 ，接著進行HWE反應完成天然物的內酯環(lactone ring)支鏈的建立。最後使用RhCl3試劑進行雙鍵的位移而得到天然物 solidagolactone IV，將solidagolactone IV進行PCC氧化可得天然物solidagolactone V。使用Meyers教授發表的掌性輔助基 109可以合成出具有光學活性的中間物 (-)-77 ，其是用來進行天然物solidagolactone IV (62) 及V (63) 的不對稱合成的中間體。

Abstract

The total synthesis of naturally occurring cis-clerodanoids solidagolactone IV and V has been accomplished in 16 and 17 linear steps respectively with the key step being a Diels-Alder cycloaddition to construct the bicyclic core common to both natural products. Starting from ethoxy enone 45, Stork-Danheiser alkylation with 4-bromo-1-butene gave enone 76 which was reduced and hydrolyzed to afford enone 77 in excellent yield. Cyano enone 80 was then arrived at from enone 77 via an established protocol of formylation (77 □ 78), isoxazole formation (78 □ 79), and base promoted fragmentation (79 □ 80). The dienophilic carbon-carbon double bond was installed by treatment of enone 80 with DDQ under basic conditions, giving dienophile 73. Zinc (II) iodide mediated Diels-Alder cycloaddition of trans-piperylene with dienophile 73 furnished cycloadduct 82 possessing 3 of the 4 contiguous stereogenic centers present in the target molecules in the correct fashion. Reductive methylation of enone 82 afforded enone 84 with complete stereoselectivity which was subsequently subjected to a 1,4-addition reaction with lithium dimethylcuprate in the presence of trimethylsilyl bromide to install the final stereocenter found in the target natural products, yielded ketone 85. Treatment of ketone 85 with lithium aluminum hydride furnished alcohol 95 in a highly stereoselective manner, the alkoxy of which was protected as the MOM ether (95 □ 102). Wacker oxidation of the terminal olefin present in compound 102 afforded methyl ketone 100 which oxidized to hydroxy ketone 101 in a 2-step process. Hydroxy ketone 101 was treated with triethyl phosphonoacetate under Horner Wadsworth Emmons reaction conditions to give butenolide 106 which was subsequently treated with rhodium trichloride in refluxing ethanol to complete the total synthesis of solidagolactone IV. From there, oxidation with pyridinium chlorochromate realized the total synthesis of solidagolactone V. The particulars of the abovementioned total syntheses is detailed in this thesis.

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