Asymmetric Synthesis of Polyethers

聚醚的不对称合成

• 批准号: 7011138
• 负责人: MICHAEL T. CRIMMINS
• 金额: $ 28.03万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-02-01 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7011138
• 关键词: alkenes; biological products; brevetoxin; chemical reaction; chemical synthesis; cyclic compound; drug design /synthesis /production; elastomers; ethers; molecular asymmetry

DESCRIPTION (provided by 8applicant): The specific aims of this program are to develop a practical, flexible strategy for the enantioselective synthesis of six to nine membered ring ethers and apply the new strategies to the total synthesis of structurally novel and biologically important natural products. During the course of this investigation, new synthetic technologies will be explored for the asymmetric construction of medium ring ethers via olefin metathesis and tandem ring closing olefin metathesis reactions. Convenient access to alpha, alpha'-disubstituted ether linkages with control of the absolute stereochemistry at the positions alpha to the ether linkage is critical to the overall success of this program. Two important new approaches have already evolved from this program: 1) a syn or anti selective aldol reaction of chlorotitanium enolates of glycolyl oxazolidinethiones and 2) a highly versatile asymmetric glycolate alkylation reaction for the construction of alpha, alpha'-disubstituted ethers. Completion of the syntheses of brevetoxin A, gigantecin and mucocin are anticipated during the next grant period. Further development of the general approach to medium ring ethers will focus on the development of an intramolecular Diels-Alder approach to the eunicellin and cladiellin class of diterpenes including the cytotoxic agents astrogorgin and 4-Deoxyasbestinin A. A new strategy for the rapid construction of cis-2,6-distubstituted tetrahydropyrans that establishes both the C2 and the C6 stereogenic centers in a single step will also be investigated and applied to the total synthesis of the cytotoxin lasonolide A.

描述（由8 Applicant提供）：该计划的具体目的是为六到九个成员的环际以对映选择性合成制定实用，灵活的策略，并将新策略应用于结构上新颖和生物学重要的天然产物的总合成。在这项研究过程中，将通过烯烃的分解和串联环关闭烯烃的元理解反应来探索新的合成技术，以探索中环醚的不对称结构。方便访问Alpha，Alpha'-DisubStestured Ether链接，并控制Alpha位置的绝对立体化学与以太链接的控制对于该程序的整体成功至关重要。该程序已经进化了两种重要的新方法：1）糖基类黄酮二硫代酮的叶绿素烯烃的Syn或抗选择性醛醇反应，以及2）高度用途的不对称甘草烷基化烷基化烷基化烷基化烷基化反应，以构建Alpha，Alpha'-disbha'disbla'disubstateuted Ethers。预计将在下一个赠款期间完成Brevetoxin A，Gigantecin和Mucocin的合成。对中环醚的一般方法的进一步发展将集中在开发甲戊烯二苯甲酸和克拉二烯类的室内双代alder方法的发展上单个步骤中的中心也将被研究并应用于细胞毒素Lasonolide A的总合成。