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Organocatalytic Domino Michael-Aldol Reactions for the Construction of Heterocyclic Natural Products

有机催化多米诺迈克尔-羟醛反应构建杂环天然产物

基本信息

批准号：
122350281
负责人：
Professor Dr. Stefan Bräse
金额：
--
依托单位：
Institut für Organische Chemie (IOC)
依托单位国家：
德国
项目类别：
Priority Programmes
财政年份：
2009
资助国家：
德国
起止时间：
2008-12-31 至 2010-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/122350281?language=en
关键词：
Organocatalytic Domino Michael Aldol Reactions

项目摘要

A large number of natural products contain heterocycie motifs. Although many approaches have been used, there are only few organo-catalytic domino reactions known in the literature. In this project, aldol/vinylogous aldol and Michael reactions will be combined with organo catalysis to give chiral complex heterocycie scaffolds. In particular, the natural products yaequinolone, lachnone C and marmycin A will be synthesized for the very first time. Yaequinolones are polycyclic chiral chromenes. They were isolated from the culture broth of the fungal strain Penicillium sp. FKI-2140 and showed growth inhibitory activity against brine shrimp {Artemia salina). Lachnone C is a recently isolated chromone, isolated from the filamentous fungus Lachnum sp. BCC 2424. Lachnones mildly inhibited the growth of Mycobacterium tuberculosis. Using the reaction sequence outlined above, we will synthesize the heterocyclic part of the marmycins. They are new cytotoxic quinones of the angucycline class and were isolated from the culture broth of a marine sediment-derived actinomycete related to the genus Streptomyces. The gross structures and absolute configurations of both compounds were determined by spectroscopic and crystallographic methods. Marmycin A displayed significant cytotoxicity against several cancer cell lines, some at nanomolar concentrations. For marmycin A, tumor cell cytotoxicity appeared to coincide with induction of modest apoptosis and arrest in the GI phase of the cell cycle.

大量的天然产物含有杂环基序。虽然已经使用了许多方法，但文献中已知的有机催化多米诺反应很少。在本项目中，将醛醇/葡萄醛醇与Michael反应结合有机催化得到手性配合杂环支架。其中，首次合成了天然产物马霉素A、拉奇诺酮C、马霉素A。萘醌是一种多环手性铬。从真菌青霉菌菌株FKI-2140的培养液中分离得到的3个菌株对盐碱对虾（Artemia salina）有生长抑制作用。Lachnone C是最近从丝状真菌Lachnum sp. BCC 2424中分离到的一种色素。拉克农内酯对结核分枝杆菌的生长有轻度抑制作用。根据上述反应顺序，我们将合成马霉素的杂环部分。它们是从链霉菌属的一种海洋沉积物源放线菌培养液中分离出来的新的细胞毒性醌类药物。用光谱学和晶体学方法测定了两种化合物的总体结构和绝对构型。马霉素A对几种癌细胞表现出显著的细胞毒性，其中一些达到纳摩尔浓度。对于马霉素A，肿瘤细胞毒性似乎与诱导适度凋亡和细胞周期的GI期阻滞相一致。