不對稱全合成(-)-Isooncinotine與擬全合成Zoapatanols－結合環閉合置換反應和甲酸還原反應

Asymmetric Synthesis of (-)-Isooncinotine and Formal Syntheses of Zoapatanols by Ring-Closing Metathesis/Regioselective Formate Reduction

鄭秀宜(Hsiu-yi Cheng)

指導教授 ： 侯敦仁

國立中央大學/理學院/化學系/博士(2011年)

摘要

此論文有兩篇主題，首先是結合環閉合置換反應（ring closing metathesis）和位置選擇性甲酸還原反應（regioselective formate reduction）得到環外烯烴化合物的方法。開發以氯化烯丙基鈀（II）二聚物（allylpalldium chloride dimer）、二-三級丁基 2-聯苯基膦（di-tert-butyl 2-biphenylphosphine）、甲酸和三乙胺在N,N-二甲基甲醯胺溶劑下還原烯丙基酯（allylic acetate），可以有很好的區域選擇性和高產率得到環外烯烴（exocyclic olefins）結構，並利用此方法完成(-)-zoapatanol擬全合成（formal synthesis）。此不對稱合成以 (L)-蘋果酸（L-malic acid）衍生之內酯為起始物，藉由螯合控制（chelation control）進行親核性醯基加成反應（nucleophilic acyl addition）後得到zoapatanols結構中相鄰的兩個不對稱中心並且有很好的非鏡像選擇性。氧化、烴烯化、丙烯化、環閉合置換反應以及鈀金屬催化甲酸還原反應後得到關鍵中間物達成此擬全合成。
第二個主題是不對稱合成(-)-isooncinotine。利用(1S)-樟腦磺酸將外消旋的2-六氫吡啶基乙醇（2-piperidineethanol）作拆分（resolution）後，得到單一光學異構物作為起始物。然後作醯化、Michael加成和以三氫化鋁還原得到spermidine的骨架。環閉合置換反應形成具有22員環的內醯胺。我們發現以四氫化鋁鋰還原時會進行Michael加成的逆反應，因此深入研究四氫化鋁鋰或三氫化鋁還原β位置上具有醯胺或胺集團丙腈之差異。

關鍵字

還閉合置換反應 ； 甲酸還原反應

並列摘要

There are two topics in the thesis. The first is formal syntheses of zoapatanols by ring-closing metathesis/regioselective formate reduction.
The combination of ring-closing metathesis and regioselective formate reduction is an effective strategy for the synthesis of cyclic compounds with exo olefins. Reduction of allylic acetates, formed by ring-closing metathesis, using allylpalladium chloride dimer, di-tert-butyl 2-biphenyl-phosphine, and formic acid/ triethylamine in DMF gives the exo-cyclic olefins with excellent regioselectivity and high yields under a mild condition. Synthetic application to prepare zoapatanols is accomplishing. The key vicinal stereocenters in zoapatanol were constructed from the L-malic acid dericed lactone by the nucleophilic acyl addition with excellent diastereoselectivities. Then the oxidation, Olefination, subtle allylation, RCM and Pd-formate reduction to get the key intermediums。
The second is asymmetric synthesis of (‒)-isooncinotine. The asymmetric total synthesis of the macrocyclic spermidine alkaloid isooncinotine, was completed by efficient RCM from resolution of 2-piperidineethanol as a starting material. Michael addition, amidations, and aluminum hydride reduction were applied to form the moiety of spermidine. Retro-Michael addition was observed when β-amido- and β-amino-propionitriles were reduced by LAH. The effects of LAH versus AlH3 were discussed.

並列關鍵字

RCM ； Zoapatanol ； Isooncinotine ； formate reduction ； ring-closing metathesis

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