【作者】 李洋；

【导师】 曹小平；

【作者基本信息】 兰州大学 ， 有机化学， 2006， 博士

【摘要】 本论文主要探讨了酰胺结构天然产物的全合成研究,进行了海洋天然产物malyngamides U,V的全合成,并利用Ramberg-Backlund反应合成了一系列天然共轭多烯酰胺生物碱,同时对本组发现的氢化铝锂还原α,β-不饱和羰基化合物的新反应做了进一步研究。论文共分为四章: 首先综述了合成malyngamides U,V的手性源香芹酮近年来在天然产物合成中的应用,根据它在各类天然产物骨架构筑中的不同作用进行归类,指出了天然手性源香芹酮在这些天然产物合成中的重要作用。 第2章详细介绍了具有新颖骨架结构的海洋天然产物malyngamides U,V的全合成研究。首先,对malyngamides类酰胺化合物进行了结构分析,综合归属介绍。其次,对malyngamides U,V的手性长链脂肪酸部分(-)-(4E,7S)-7-甲氧基-4-十二烯酸进行了合成,以正己醛的不对称烯丙基化反应和在t-BuLi存在下的手性末端炔和保护的3-溴-1-醇进行的S_N2偶联反应为关键步骤,通过8步反应以24%的总产率完成了其合成。同时以天然手性源(S)-香芹酮为起始原料完成了malyngamide U的全合成。在合成中,以(S)-香芹酮的羟甲基化反应和不对称Henry反应为关键步骤,通过关键中间体的单晶结构,不对称Henry反应,以及相关的1D NOESY实验等重要环节完成了天然产物malyngamide U的结构修正,并通过旋光实验确定了它的绝对构型。另一方面,以Evans-aldol反应为关键步骤对malyngamide V氨部分的六元环骨架构筑进行了初探,为进一步合成积累了经验。 第3章将本组在Ramberg-Backlund反应方面的研究拓展到共轭多烯酰胺生物碱的合成中。以该反应为关键步骤合成了13个具有吡咯烷,异丁基或哌啶结构的天然生物碱和一个类似物。 第4章在本组工作的基础上,深入研究了由氢化铝锂还原α,β-不饱和酯和α,β-不饱和酮制备1,3-二醇的方法,该方法有望应用到含有1,3-二醇骨架结构的天然产物合成中。更多还原

【Abstract】 This thesis is concerning on the synthesis of malyngamides U, V as well as the application of Ramberg-Backlund reaction to the synthesis of naturally occurring unsaturated amide alkaloids. Additionally, a novel reaction of α,β -unsaturated esters and ketones with lithium aluminum hydride was studied based on our group research. It mainly consists of the following four parts:First, we summarized the recent application of carvone which served as a narural chiral pool for the synthesis of malyngamides U and V in the synthesis of the natural products on the basis of the different function in construction of the skelecton. It was pointed out the importance of carvone in the natural product synthesis.In chapter 2, the total synthesis of malyngamides U, V was introduced detailedly. At first, a brief introduction of malyngamides was given. After that, a stereoselective synthesis of (-)-(4E,7S)-7-methoxydodec-4-enoic acid which is the acid portion of malyngamides U and V was accomplished in eight steps from hexanal in 24% overall yield. The key steps involved the catalytic asymmetric allylation of hexanal and the coupling reaction of a chiral alkyne and a protected bromide in the presence of t-BuLi. Then the structural revision and determination of absolute configuration of malyngamide U were presented by first total synthesis. Natural chiral pool (S)-carvone was selected as starting material. The key steps involved a hydroxymethylation of (S)-carvone and an asymmetric Henry reaction of key aldehyde. At last, the synthesis of malyngamide V was investigated. During the course Evans-aldol reaction was as the key step for the construction of the six membered ring of the amine portion.In chapter 3, based on the work of our lab, 13 naturally occurring unsaturated amide alkaloids bearing pyrrolidine, isobutyl and piperidine moieties and one analogue were synthesized by Ramberg-Backlund reaction.At last, a novel reaction of reduction of α,β-unsaturated esters and ketones with lithium aluminum hydride to afford 1,3-diol was presented based on our work. Direct application can be expected in the synthesis of the natural products containing 1,3-diol structural unit.更多还原