ACYCLIC DIASTEREOSELECTION: METHODOLOGY AND SYNTHESIS

无环非对映选择：方法和合成

• 批准号: 6628804
• 负责人: WILLIAM R ROUSH
• 金额: $ 24.5万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 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 2004-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6628804
• 关键词: allyl compound; antineoplastic antibiotics; boronic acids; catalyst; chemical synthesis; drug design /synthesis /production; ketal; lactones; macrolide antibiotics; marine toxins; pyrans; stereochemistry; stereoisomer

We propose to continue our research in the area of acyclic diastereoselective synthesis, with emphasis on novel allylmetalation reactions and fragment assembly aldol reactions which will be developed in the context of the total synthesis of structurally complex, biologically active natural products. Specific goals for the next grant period are: (1)Completion of a Total Synthesis of Tedanolide. The key step of the proposed synthesis was successfully modeled in the previous grant period, thus defining the strategy that will be pursued for completion of the total synthesis. (2) Allylation of Oxonium Ions; Synthesis of the Pyran Nucleus of Scytophycin C. A new strategy for the synthesis of the 2,6-trans dihydropyran unit of scytophycin C will be developed based on the reactions of allylsilanes and oxonium ions followed by ring closing metathesis. (3) Completion of a Total Synthesis of Scytophycin C. The total synthesis of scytophycin C will be completed. The key fragment assembly aldol step was successfully modeled in the previous grant period. (4) Total Synthesis of Spongistatin 1. A synthesis of the E-F bis-pyran unit was completed in the preceding grant period. Studies in the coming grant period will focus on the bifunctional gamma-silylallylborane for the convergent coupling of two aldehydes to generate l,5-anti-pent-2(E)-1,5- diols, which will serve as precursors to the A-B and C-D spiroketals. A strategy for the stereocontrolled synthesis of the C-D spiroketal via inversion of the C(l9) stereocenter also will be developed. (5) Total Synthesis of Apoptolidin. Fragment assembly aldol reactions of alpha- alkoxy ketones will be developed for the synthesis of the C(12)-C(28) segment of apoptolidin. (6) Total Synthesis of Amphidinol 3. Bifunctional allylboranes will be developed for the convergent coupling of two aldehydes to generate l ,5-syn-pent-2(Z)- l ,5-diols, which will serve as key intermediates for the synthesis of the tetrahydropyran units of amphidinol 3. This methodology also provides an alternative strategy for synthesis of the scytophycin C dihydropyran nucleus.

我们建议继续我们的研究领域的非环状非对映选择性合成，重点是新的烯丙基金属化反应和片段组装羟醛缩合反应，这将是发展的背景下，结构复杂，生物活性的天然产物的全合成。下一个赠款期的具体目标是：（1）完成Tedanetum的全面综合。 建议的综合的关键步骤是成功地模拟在前一个赠款期，从而确定了战略，将追求完成总合成。(2)氧鎓离子的烯丙基化反应;蓝柄藻素C吡喃核的合成。基于烯丙基硅烷与氧鎓离子的反应以及随后的关环复分解反应，发展了一种新的策略来合成scytophycin C的2，6-反式二氢吡喃单元。 (3)Scytophycin C全合成的完成 完成了scytophycin C的全合成。关键的片段组装羟醛缩合步骤已在前一个授权期成功建模。(4)Spongistatin的全合成1. E-F双吡喃单元的合成在前一个资助期完成。在未来的资助期内，研究将集中在双官能γ-甲硅烷基烯丙基硼烷用于两种醛的会聚偶联以生成1，5-反式-β-2（E）-1，5-二醇，其将作为A-B和C-D螺缩酮的前体。还将发展通过C（19）立构中心的反转立体控制合成C-D螺缩酮的策略。(5)Apoptolidin的全合成。α-烷氧基酮的片段组装Aldol反应将被开发用于合成雷公藤甲素的C（12）-C（28）片段。(6)Amphidinol的全合成3.双官能烯丙基硼烷将被开发用于两种醛的会聚偶联以产生1，5-顺式-正-2（Z）-1，5-二醇，其将充当用于合成氨杂环丁二醇3的四氢吡喃单元的关键中间体。这种方法也提供了一种替代策略的scytophycin C二氢吡喃核的合成。