ASYMMETRIC REACTIONS OF PROCHIRAL KETONES

前手性酮的不对称反应

• 批准号: 3466718
• 负责人: Jeffrey Aube
• 金额: $ 8.78万
• 依托单位: UNIVERSITY OF KANSAS LAWRENCE
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3466718
• 关键词: 6,7 benzomorphan; alkaloids; aminoacid analog; analgesics; carnitine; cyclohexanones; drug design /synthesis /production; epoxides; heterocyclic compounds; imines; ketones; lactones; nitrogen; photolysis; protonation; stereochemistry; stereoisomer; yohimbine

Several related techniques to effect the synthesis of optically active heterocycles are proposed. These methods, which involve the use of diastereotopic group selectivity, can be separated into two general classes. A scheme for the synthesis of optically active lactones is based on a synthetic equivalent of an asymmetric Beckmann rearrangement. In this plan, a prochiral ketone (such as a 4- substituted cyclohexanone or a meso-bicyclic structure) is converted into a imine bearing a chiral substituent on nitrogen, which is then stereospecifically oxidized to an oxaziridine. These materials then undergo a stereospecific rearrangement reaction upon photolysis, affording (after removal of the chiral substituent on nitrogen) enantiomerically enriched lactams. In addition, enantiospecific deprotonations and enamine reactions are proposed in order to effect stereocontrol at distal stereocenters in the proposed substrates. This technology can then intersect with standard insertion (Beckmann, Baeyer- Villager) chemistry to yield heterocycles with substituent patterns that are complementary to those achieved in the scheme above. The chemistry proposed will be applied to three classes of organic medicinal agents, each of which has been shown to be biologically active or inactive depending on absolute configuration: carnitine and other gamma-amino acids, the benzomorphinan analgesics, and the yohimbine alkaloids. Finally, a novel scheme to control regioselectivity on nearly- symmetrical double bonds or epoxides will be presented.

影响光学合成的几种相关技术 提出了活性杂环。 这些方法，包括 利用非对映异构基团的选择性，可以分离成 两个普通类。 光学活性内酯的合成方案是基于 一种合成的不对称贝克曼 重排 在该方案中，将前手性酮（例如4-甲基-N-苯基-N-甲基-N 取代的环己酮或内消旋双环结构）， 转化成在氮上带有手性取代基的亚胺， 然后将其立体特异性氧化成氧氮丙啶。 这些 然后材料进行立体定向重排反应， 在光解后，得到（在除去手性取代基后 对氮）对映体富集的内酰胺。 此外，对映体特异性去质子化和烯胺反应 为了在远端实现立体控制， 在所提出的基板中的立体中心。 这项技术可以 然后与标准插入相交（Beckmann，Baeyer， 产生具有取代基模式的杂环的化学 这是对上述方案所实现的目标的补充。 所提出的化学方法将应用于三类有机化合物 药物制剂，其中每一种都已被证明是生物学上的 活性或非活性取决于绝对构型：肉毒碱 和其他γ-氨基酸，苯并吗啡喃镇痛剂， 和育亨宾生物碱。 最后，提出了一种控制近红外区域选择性的新方案 将呈现对称的双键或环氧化物。