APPLICATIONS OF IRON COMPLEXES TO ORGANIC SYNTHESIS

铁配合物在有机合成中的应用

基本信息

批准号：
6385944
负责人：
William A Donaldson
金额：
$ 14.75万
依托单位：
MARQUETTE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-07-01 至 2003-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6385944
关键词：
alkylation antibacterial agents antibiotics antifungal agents antiviral agents biological products chemical synthesis cyclopropanes diene drug design /synthesis /production iron compounds metal complex polyenes stereochemistry

项目摘要

The long range goal of our research is to develop new synthetic methodology for the construction of C-C bonds in a stereospecific fashion. This new methodology will be useful for the preparation of polyene macrolides and for the preparation of cyclopropane containing natural products. In particular, we wish to utilize the ability of an ironcarbonyl adjunct: a) to control the stereochemistry of conjugated dienes and to protect the diene against reduction oxidation, and cycloaddition reactions; b) to control the relative stereochemistry at asymmetric centers adjacent and remote to a conjugated diene; c) to control the relative stereochemistry of trisubstituted cyclopropanes; d) to control the relative stereochemistry at asymmetric centers adjacent to a trans-disubstituted cyclopropane. As vehicles for demonstration of these methodologies, we have chosen macrolactin A, madumycin II, ambruticin, 2-(2'- carboxycyclopropyl) glycines, and FR-900848 as targets. Macrolactin A was isolated from an unidentified deep sea bacterium. This compound exhibits antiviral activity against Herpes Simplex I and II and against HIV in initial tests. Since the culturing of this bacterium has been "unreliable", further biological research must rely on total synthesis. Madumycin II is a member of the streptogramin A family of antibiotics which are active against Gram-positive organisms. Ambruticin is a structurally complex antifungal agent. This compound was found to be orally active against systemic infections of histoplasmosis and coccidiomycosis. Several 2-(2'-carboxycyclopropyl)glycines have been found to be potent ligands for metabotropic glutamate receptors. FR-900848 is a polycyclopropane molecule isolated from the fermentation of Streptoverticillium fevens which inhibits filamenteous fungi such as Aspergillus niger, but has relatively low toxicity in mammals (LD50 greater than 1g/1kg).

我们研究的远距离目标是开发新的合成在立体特定中构建C-C键的方法时尚。这种新方法将对准备多烯大环内酯类以及用于含有环丙烷的制备天然产品。特别是，我们希望利用辅助辅助：a）控制共轭的立体化学二烯并保护二烯免受还原氧化，并环加成反应； b）控制相对立体化学邻近的不对称中心和与共轭二烯的遥控中心； c）到控制三取代的环丙烷的相对立体化学； d）控制不对称中心的相对立体化学毗邻反式取代的环丙烷。作为证明这些方法论的车辆，我们选择了大元A，Madumycin II，Ambruticin，2-（2'-羧基丙烷）甘氨酸和FR-900848作为靶标。从一个从一个身份不明的深海细菌。该化合物表现出抗病毒针对单纯疱疹I和II的活动以及初始对艾滋病毒的活动测试。由于这种细菌的培养是“不可靠的”，所以进一步的生物学研究必须依赖于总合成。 Madumycin II 是链球菌素的成员A抗生素家族活跃于革兰氏阳性生物。 Ambruticin在结构上是复杂的抗真菌剂。发现该化合物是口服活性的针对组织胞浆病和球霉症的全身感染。已经发现几种2-（2'-羧基环丙丙基）甘氨酸是有效的代谢型谷氨酸受体的配体。 FR-900848是从发酵的多环丙烷分子抗链球菌fevens，抑制丝状真菌，例如尼日尔曲霉，但在哺乳动物中的毒性相对较低（LD50 大于1g/1kg）。