Applications of the Stereoretentive O and C Rearrangemen

立体保留O和C重排的应用

• 批准号: 6623333
• 负责人: Tomislav Rovis
• 金额: $ 22.12万
• 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/6623333
• 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）本研究的总体目标是 开发立体选择性方法， 碳-碳键，以提供快速、高效和选择性的路线 生物活性分子。这些类型的键存在于许多 天然产品目标。特特拉姆酸结构上相关的一类 大环内酰胺，其特征在于多取代的双环（3.3.0）核和 连接在大环内酰胺内特特拉姆酸部分可通过此 方法论它们具有根本的意义，因为这类成员 表现出多样的生物活性特征。阿托米特展品 对B16黑色素瘤细胞的细胞毒性。Geodin A是一种有效的杀线虫剂， 剂Alteramide A对小鼠白血病P388细胞显示细胞毒性， 小鼠淋巴瘤L1210细胞和人表皮样癌KB细胞， 体外Discodermide抑制体外培养的小鼠P388细胞增殖 白血病细胞，并具有一定的抗真菌活性。发现Aburatubolactam A 抑制超氧阴离子产生，而阿武拉土内酰胺C诱导细胞凋亡。 本研究的中心方法是将手性乙烯基醚转化为 相应的碳-碳键保留了立体化学。这 该策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。 具体而言，本研究的目标是：1）开发和探索范围 乙烯基缩醛的立体保留O到C重排; 2）应用此 洞察一般乙烯基醚O到C重排的发展， 探讨其局限性; 3）探索立体定向的新方法 乙烯基醚，以扩大立体保留的范围O到C 乙烯基缩醛和醚的重排; 4）将这些研究扩展到 用其它亲核试剂对手性醚进行立体保留取代; 5） 发展对这些反应的机械理解; 6）将 立体保留O至C重排，随后转化为 促进与梯形毒素相关的寡聚吡喃的快速组装 天然产物家族; 7）以立体选择性的方式实施这些方法。 合成特特拉姆酸大环内酰胺如柱酰胺。