CHIRAL CROTYLBORONATES: METHODOLOGY AND SYNTHESIS

手性巴豆基硼酸酯：方法学和合成

• 批准号: 3294873
• 负责人: WILLIAM R ROUSH
• 金额: $ 17.9万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-02-01 至 1996-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3294873
• 关键词: aldehydes; allyl compound; antibiotics; boron; boronic acids; catalyst; chemical synthesis; croton oil; drug design /synthesis /production; enol; enolate; ionophores; ketones; macrolide antibiotics; propionates; quinones; silanes; stereochemistry; stereoisomer

The efficient stereo- and enantioselective synthesis of complex arrays of acyclic stereocenters constitutes one of the most intriguing challenges in modern synthetic organic chemistry. The multitude of such acyclic arrays in macrolides, polyether antibiotics, complex carbohydrates and numerous other classes of biologically active natural products has provided considerable stimulus for the development of synthetic methodology that is practical, efficient, and applicable to a wide range of problems. The major objectives of this research program continue to be (1) the development of a family of highly enantioselective chiral allyl- and crotylboronates and (2) the application of this technology in the synthesis of biologically active, propionate-derived natural products. The tartrate ester modified allylboronates 1-3 developed in our laboratory function beautifully in matched double asymmetric reactions but often give less satisfactory results in mismatched double asymmetric reactions. Consequently, additional effort will be devoted to the development of improved, second generation reagents 63 and 68-70. Our observation that the % e.e. of the allylborations of unsaturated aldehydes is significantly enhanced by using metal carbonyl complexes as substrate surrogates will be applied in enantioselective syntheses of carbocyclin and of a key rutamycin B intermediate (124). Syntheses of streptovaricin D and bafilomycin A1 initiated in the previous grant period will be completed, and syntheses of zincophorin and rutamycin B will be initiated in the later years of this grant. Methods for construction the unusual quinone methide unit of streptovaricin D must be developed. A stereochemical study of the reactions of gamma-methoxyallylchromium and chiral aldehydes will be completed in connection with the bafilomycin synthesis, and additional studies into the factors that control the stereochemistry of the bafilomycin aldol coupling reaction (55 and 28) will be performed. Aldol reactions for fragment assembly steps in the rutamycin synthesis also will be examined. These studies provide the opportunity to define the stereochemical preferences of the Lewis acid catalyzed aldol reactions of enol silanes prepared from chiral alpha-methyl ketones, the results of which will be of considerable significance particularly if substantial selectivity is observed.

高效的立体选择性和对映选择性合成的复杂阵列的 无环立体中心构成了最有趣的挑战之一， 现代合成有机化学 这种非循环数组的数量 在大环内酯类、聚醚类抗生素、复合碳水化合物和许多 其它种类的生物活性天然产物已经提供了 对合成方法学的发展有相当大的刺激作用， 实用，高效，适用于广泛的问题。 该研究计划的主要目标仍然是（1） 开发了一类高对映选择性的手性烯丙基-和 巴豆基硼酸酯;（2）该技术在合成中的应用 具有生物活性的丙酸衍生天然产物。 该酒石酸盐 酯改性烯丙基硼酸酯1-3在我们的实验室功能开发 在配对的双不对称反应中表现得很好，但通常 在不匹配的双重不对称反应中获得了满意的结果。 因此，将作出更多努力， 改进的第二代试剂63和68-70。 我们观察到 % e. e.的烯丙基硼化的不饱和醛是显着的 通过使用金属羰基络合物作为底物替代物， 应用于碳环素和关键的芸香霉素的对映选择性合成 B中间体（124）。 静脉曲张链菌素D和巴弗洛霉素A1的合成 在前一个赠款期内启动的项目将完成， 锌磷蛋白和鲁塔霉素B将在本报告的后几年开始使用。 格兰特. 不寻常的醌甲基化单元的构建方法 必须开发静脉曲张链菌素D。 的立体化学研究 γ-甲氧基烯丙基铬和手性醛的反应将是 与巴弗洛霉素合成相关完成，以及另外的 研究了控制立体化学的因素， 进行巴弗洛霉素羟醛偶联反应（55和28）。 羟醛 在如他霉素合成中用于片段组装步骤的反应也将 接受检查。 这些研究提供了一个机会， 刘易斯酸催化的羟醛缩合反应的立体化学偏好 由手性α-甲基酮制备的烯醇硅烷， 这将是相当重要的，特别是如果大量的 观察到选择性。