【作者】 顾大伟；

【导师】 郭勋祥；

【作者基本信息】 上海交通大学 ， 生物学， 2016， 硕士

【摘要】 吲哚并[2,3-c]吡喃酮及噻吩并[2,3-c]吡喃酮类化合物是一类重要的杂环化合物,其结构单元广泛存在于许多天然产物和生物活性的物质中。近年来的研究表明该类化合物在治疗癌症、抑制肿瘤生长等方面有着潜在的开发价值。目前,吲哚并[2,3-c]吡喃酮及噻吩并[2,3-c]吡喃酮类化合物的合成方法,主要有以下几种:一是使用钯、铑、钌、金等贵重金属作为催化剂;二是使用铜或铁金属作为促进剂,但这类体系需要使用当量的金属盐才能有效促进反应;三是使用无金属的反应体系,然而,该类体系往往存在着底物需要多步反应的预官能化,或者需要苛刻的反应条件,诸如高温,超声等。由于以上合成方法都存在一定的局限性,阻碍了该类化合物性质的进一步研究。因此,如何开发出高效构建该类化合物的合成方法成为人们关注的一个热点。本论文使用廉价、低毒的金属铜盐作为催化剂,通过使用易于制备的β-卤代-α,β-不饱和羧酸和炔烃化合物作为底物,高效构建了一系列吲哚并[2,3-c]吡喃酮及噻吩并[2,3-c]吡喃酮化合物。本论文以1-甲基-3-碘-吲哚-2-甲酸和丁炔二酸二甲酯作为模块反应,研究了各种反应条件,包括铜盐、碱、溶剂、温度、反应时间等对反应体系的影响。此外还考察了不同取代基的β-卤代-α,β-不饱和羧酸和炔烃化合物在最优反应条件下的兼容性,借助这一催化体系,一些新颖的吲哚并[2,3-c]吡喃酮及噻吩并[2,3-c]吡喃酮化合物能够以较好的产率被合成出来。本论文将为构建吲哚并[2,3-c]吡喃酮及噻吩并[2,3-c]吡喃酮化合物提供一种简单、高效的合成方法,这一合成方法将进一步促进吲哚并[2,3-c]吡喃酮及噻吩并[2,3-c]吡喃酮化合物的性质研究。更多还原

【Abstract】 Indolo[2,3-c]pyrane-1-ones and thieno[2,3-c]prane-7-ones are ones of the important heterocycles,which exist extensively in many natural products and biologically active compounds.Especially,they have shown anti-cancer potential and inhibiting tumor cell growth based on recent reports.There are several methodologies for the synthesis of indolo[2,3-c]pyrane-1-ones and thieno[2,3-c]pyrane-7-ones.For example,most reported cases used expensive transition-metal complexes,such as palladium,rhodium,ruthenium,and gold as the catalyst.The examples,which use inexpensive transition-metal complexes of copper and iron,suffered from the need of stoichiometric amounts of metals.Other examples did not use transition-metal complexes,however,the reactions have to prepare the functional substrates by mutil-steps or activate the inert substrates by harsh reaction conditions,such as high temperature or microwaves.The study of these compounds’ properties is confined by the disadvantages as mentioned above.As a result,the development of an efficient synthetic method for the synthesis of indolo[2,3-c]pyrane-1-ones and thieno[2,3-c]pyrane-7-ones has attracted considerable attention.In this thesis,we used a copper salt,which is low cost and low toxicity,as a catalyst to develop an effective method for the synthesis of indolo[2,3-c]pyrane-1-ones and thieno[2,3-c]pyrane-7-ones from easily available heteroaromatic β-halo-α,β-unsaturated carboxylic acids with alkynes.We chose 1-methyl-3-iodo-indole-2-carboxylic acid and dimethyl acetylenedicarboxylate as the model starting materials to test the reaction conditions,such as copper salts,bases,solvents,reaction temperature and reaction time.Futhermore,the tolerance of different functional groups was tested under the optimal condition,and a series of indolo[2,3-c]pyrane-1-ones and thieno[2,3-c]pyrane-7-ones were obtained in moderate to good yields.This thesis provides a simple and efficient strategy for the synthesis of indolo[2,3-c]pyrane-1-ones and thieno[2,3-c]pyrane-7-ones,and further benefits the research of these compounds’ properties.更多还原