APPLICATIONS OF IRON COMPLEXES TO ORGANIC SYNTHESIS

我们研究的长期目标是开发新的合成材料 立体定向构筑C-C键的方法学 时尚。这一新的方法将有助于编制 多烯大环内酯类化合物及其环丙烷的制备 天然产品。特别是，我们希望利用一个 铁羰基辅助剂：a)控制共轭化合物的立体化学 保护二烯和保护二烯免受还原氧化，以及 环加成反应；b)将相对立体化学控制在 与共轭二烯相邻和远离的不对称中心；c)至 控制三取代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 与反式二取代环丙烷相邻。 作为演示这些方法的工具，我们选择了 大乳酸菌素A，马杜霉素II，牛乳素，2-(2‘-羧基环丙基) 甘氨酸和FR-900848为靶点。大乳酸菌素A是从一种 不明深海细菌。这种化合物具有抗病毒作用。 抗单纯疱疹病毒I型和II型及HIV的初步活性 测试。由于这种细菌的培养一直是“不可靠的”， 进一步的生物学研究必须依靠全合成。马杜霉素II 是链球菌素A家族的成员，这种抗生素是 有效对抗革兰氏阳性细菌。Ambrticin是一种结构上的 复合抗真菌剂。这种化合物被发现具有口服活性。 抗组织胞浆菌病和球菌病的全身感染。 已发现几种2-(2‘-羧基环丙基)甘氨酸是有效的 代谢性谷氨酸受体的配体。FR-900848是一款 从发酵液中分离出的聚环丙烷分子 Fevens链霉菌抑制丝状真菌 黑曲霉，但对哺乳动物的毒性相对较低(LD50 大于1g/1千克)。

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).