Applications of the Stereoretentive O and C Rearrangemen

立体保留O和C重排的应用

• 批准号: 6719604
• 负责人: Tomislav Rovis
• 金额: $ 22.11万
• 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/6719604
• 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：（由申请人提供）这项研究的总体目标是 开发立体选择方法以形成空间充血 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地方都发现 天然产品目标。四酸的结构相关类别 大花生酰胺的特征是多物构成的b​​icyclo（3.3.0核心和A 在大花生酰胺中连接的四酸部分，可以通过此访问 方法论。他们具有根本的利益，因为该课程的成员 表现出不同的生物学活性特征。 cylindramide展示 针对B16黑色素瘤细胞的细胞毒性。 GEODIN A是有效的绿地 代理人。替酰胺A显示针对鼠白血病P388细胞的细胞毒性， 鼠淋巴瘤L1210细胞和人类表皮癌Kb细胞中的细胞 体外。二甲剂抑制培养的鼠p388的体外增殖 白血病细胞具有一些抗真菌活性。发现aburatubolactam a 抑制超氧化物阴离子的产生，而aburatubolactam c诱导凋亡。 这项研究的核心方法是将手性乙烯基醚转化为 相应的碳碳键，并保留立体化学。这 策略利用了控制碳氧键的多种方法 立体化学将其转化为碳碳键立体化学。 具体而言，这项研究的目标是：1）开发和探索范围 乙烯基acetals的立体定位O到C重排； 2）应用此 深入了解一般的乙烯基醚O到C重排和 调查其极限； 3）探索定型生成的新方法 为了扩大立体o的范围至c的范围 乙烯基乙酰乙烯和醚的重排； 4）将这些研究扩展到 立体定位用其他亲核试剂替换手性醚； 5） 对这些反应发展机械理解； 6）夫妇 立体定位O到C重新排列，随后转换为 促进与梯子毒素相关的寡素的快速组装 天然产品家族； 7）在立体选择中实现这些方法 四酸大酰酰胺（如cylindramide）的合成。