Applications of the Stereoretentive O and C Rearrangemen

立体保留O和C重排的应用

• 批准号: 6931791
• 负责人: Tomislav Rovis
• 金额: $ 2.41万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6931791
• 关键词: chemical synthesis; ketal; lactams; molecular rearrangement; pyrans; saturated /unsaturated bonds; stereochemistry; vinyl ether

DESCRIPTION: (provided by applicant) The overall goal of this research is to develop stereoselective methods for the formation of sterically congested carbon-carbon bonds in order to provide rapid, efficient, and selective routes to biologically active molecules. These types of bonds are found in numerous natural product targets. The structurally related class of tetramic acid macrolactams, characterized by a polysubstituted bicyclo (3.3.0 core and a tetramic acid moiety connected within a macrolactam, are accessible by this methodology. They are of fundamental interest since members of this class exhibit a diverse biological activity profile. Cylindramide exhibits cytotoxicity against B16 melanoma cells. Geodin A is a potent nematocidal agent. Alteramide A shows cytotoxicity against murine leukemia P388 cells, murine lymphoma L1210 cells, and the human epidermoid carcinoma KB cells in vitro. Discodermide inhibits the in vitro proliferation of cultured murine P388 leukemia cells and has some antifungal activity. Aburatubolactam A was found to inhibit superoxide anion generation while aburatubolactam C induces apoptosis. The central approach of this research is to convert chiral vinyl ethers into the corresponding carbon-carbon bonds with retention of stereochemistry. This strategy takes advantage of the multitude of ways to control carbon-oxygen bond stereochemistry to translate it into carbon-carbon bond stereochemistry. Specifically, the goals of this research are: 1) develop and explore the scope of the stereoretentive O to C rearrangement of vinyl acetals; 2) apply this insight to the development of a general vinyl ether O to C rearrangement and investigate its limits; 3) explore new methods for the stereodefined generation of vinyl ethers in order to expand the scope of the stereoretentive O to C rearrangement of vinyl acetals and ethers; 4) extend these studies to the stereoretentive replacement of chiral ethers with other nucleophiles; 5) develop a mechanistic understanding of these reactions; 6) couple the stereoretentive O to C rearrangement with a subsequent transformation to facilitate the rapid assembly of oligopyrans relevant to the ladder toxin family of natural products; 7) implement these methods in the stereoselective synthesis of tetramic acid macrolactams such as cylindramide.

描述：(申请人提供)本研究的总体目标是 发展立体选择性方法形成立体充血 碳-碳键，以提供快速、高效和选择性的路线 到生物活性分子。这些类型的债券在许多 自然产品目标。结构上相关的四酸类化合物 大环内酰胺类，特征为多取代双环(3.3.0核心和 连接在大内酰胺中的四酸部分可通过以下方式访问 方法论。他们有根本的利益，因为这个班级的成员 展示不同的生物活动概况。环丙氨酰胺展品 对B16黑色素瘤细胞的细胞毒作用。Geodin A是一种有效的杀线虫药物 探员。Alteramide A对小鼠白血病P388细胞具有细胞毒作用， 小鼠淋巴瘤L1210细胞和人表皮样癌KB细胞 体外培养。迪可地胺抑制体外培养的小鼠P388细胞增殖 并具有一定的抗真菌活性。Aburatubolactam A被发现 抑制超氧阴离子的产生，而阿博拉坦C诱导细胞凋亡。 这项研究的中心方法是将手性乙烯基醚转化为 相应的具有立体化学保留的碳-碳键。这 战略利用多种方法来控制碳-氧键 将其转化为碳-碳键立体化学。 具体地说，本研究的目标是：1)开发和探索范围 乙烯缩醛的立体保留O到C重排；2)应用此 对一般乙烯基醚O-C重排反应发展的认识 调查它的局限性；3)探索新的方法，以适应刻板定义的一代 以扩大立体保留剂O到C的范围 乙烯缩醛和乙醚的重排；4)将这些研究扩展到 手性醚与其他亲核试剂的立体保留取代；5) 发展对这些反应的机械理解；6)将 立体保持O到C重排，随后转化为 促进与阶梯毒素相关的寡聚吡喃的快速组装 天然产物系列；7)将这些方法应用于立体选择性 圆柱胺等四酸大内酰胺类药物的合成。