CHIRAL CROTYLBORONATES--METHODOLOGY AND SYNTHESIS

手性巴豆基硼酸酯--方法学和合成

• 批准号: 2179334
• 负责人: WILLIAM R ROUSH
• 金额: $ 18.69万
• 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/2179334
• 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.

高效立体和对映体选择性合成化合物的研究 无环立体中心构成了 现代合成有机化学。这种非循环阵列的数量之多 在大环内酯类、聚醚抗生素、复合碳水化合物和许多 其他类别的生物活性天然产品提供了 对综合方法论的发展有相当大的刺激作用 实用、高效、适用范围广的问题。 这项研究计划的主要目标仍然是：(1) 一类高对映体选择性的手性烯丙基-和 巴豆基硼酸酯及其在合成中的应用 具有生物活性的丙酸衍生天然产品。酒石酸盐 本实验室开发的酯改性烯丙基硼酸酯1-3的功能 在匹配的双不对称反应中很漂亮，但通常给得较少 在不匹配的双不对称反应中得到了满意的结果。 因此，将投入更多的努力发展 改进后的第二代试剂63和68-70。据我们观察， %e.e.e。不饱和醛的烯丙基硼的含量显著地 通过使用金属羰基络合物作为底物替代品将增强 在卡环素和一种关键的柔红霉素的不对称合成中的应用 B中级(124)。链霉素D和巴菲霉素A1的合成 将完成在前一个授权期内发起的，并合成 津科普林和柔红霉素B将在今年晚些时候开始使用 格兰特。特异型甲基苯二酚装置的施工方法 必须开发链霉菌素D。一种立体化学的研究方法 γ-甲氧基烯丙基铬与手性醛的反应将是 与巴菲罗星的合成有关的完成，以及另外 人的立体化学控制因素的研究 将进行巴非霉素羟醛偶联反应(55和28)。羟醛 鲁他霉素合成中片段组装步骤的反应也将 接受检查。这些研究提供了机会来定义 路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，其结果 这将具有相当大的意义，特别是如果 观察到了选择性。