毕业论文海洋吡咯生物碱——片螺素结构简化物的合成.docVIP

Marine Alkaloids— Synthesis of the simplified analogues of Lamellarins A Thesis Submitted in Partial Fulfillment of the Requirement For the Master Degree in Applied Chemical 摘要 以廉价易得的醛、酮、α-氨基酸等为起始原料，经多步反应高效合成了系列海洋吡咯生物碱——片螺素结构简化物通过重结晶分离纯化，用、IR、NMR、熔点仪、显微镜等仪器检测和鉴定结构结果表明的合成方法能够高效合成原料中间体以及片螺素结构简化物，操作简单，放大和工业化生产药物筛选提供。论文： 第一章文献，系统介绍了海洋吡咯生物碱生物活性，以及海洋吡咯生物碱的发展、研究现状合成情况在此基础之上，提出本课题研究的科学依据设计了目标产物路线。 第二章制作了简易微管连续流反应器在40KHz的超声波作用下，反应温度在26-38?C之间，使用该反应器合成12种α，β不饱和酮，且产率达80～90％与传统的烧瓶反应相比较，反应时间由原来的1-6h缩短到10min左右。该法不但具有反应产率高、反应时间短等优点，而且可以连续、大规模地合成α，β不饱和酮（查酮）化合物。 第三章实验的α，β不饱和酮与对甲苯磺酰甲基异氰（TosMIC）合成芳香酮类片螺素结构简化物传统an Leusen方法芳香酮类片螺素结构简化物进行合成以NaH为催化剂在乙醚中进行，由于NaH一般需要在无水无氧溶剂中进行，NaH价格昂贵和乙醚闪点低，极易着火，很难放大合成以工业化生产。用NaCH2SOCH3作为催化剂DMSO为溶剂来取代NaH和乙醚金属Na和DMSO进行反应生成强碱NaCH2SOCH3，同时DMSO做溶剂，α，β不饱和酮类化合物为原料，能够方便地合成芳香酮类片螺素结构简化物。an Leusen法an Leusen法操作简单产率高催化剂价格低廉可工业化生产等。第四章α-氨基酸和二乙酰琥珀酸二乙酯Knorr-Paal 合成方法，通过路线设计和实验论证，合成得到N-羧基类吡咯生物碱并合成机理。结果表明，传统的回流反应超声波和微波在3h之内，产率可达到64～91%与传统的回流反应相比，时间短，产率高。 关键词：吡咯生物碱；片螺素；简化物；α，β不饱和酮；合成Abstract A series of the marine pyrrole alkaloids - simplified analogue of the lamellarins were synthesised by an optimized and efficient synthetic approach using the common chemicals aldehydes, ketones, and α-amino acids etc. as the starting material in multi-steps. All the compounds were purified by recrystallization and characterized by TLC, IR, 1HNMR and melting point meter. The results showed that the intermediates and simplified analogues of lamellarins can be efficiently synthesized by means of the improved synthetic method, which can help to Scale-up synthesis and to product industrialization. The significance of this work is to probe an effective method of synthesis for pyrrole alkaloids and to afford new chemical entities for drug screen. This paper was summarized as follows: The first chapter described the biological activity of the marine pyrrole alkaloids, the development situation of the marine pyrrole alkaloids, and the synthesis development , as reported in the literature. Furt