ACYCLIC DIASTEREOSELECTION: METHODOLOGY AND SYNTHESIS

我们建议继续在无环非对对选择合成领域的研究，重点是新的烯丙基金属化反应和片段组装醛醇反应，这些反应将在结构复杂，生物活性天然产物的全合成背景下发展。下一个资助期的具体目标是：(1)完成Tedanolide的全合成。拟议综合的关键步骤在前一个赠款期间成功地进行了模拟，从而确定了为完成全面综合将采取的战略。(2)氧鎓离子烯丙基化；本文提出了一种基于烯丙基硅烷与氧鎓离子反应再合环复分解合成胞霉素C 2,6-反式二氢吡喃单元的新策略。完成胞霉素C的全合成。胞霉素C的全合成将完成。关键片段组装aldol步骤在上一个授权期间成功建模。(4)海绵抑素的全合成E-F双吡喃单元的合成已在前一拨款期间完成。在接下来的资助期内，研究将集中于双功能γ -硅烯丙基硼烷，用于两种醛的聚合偶联，生成1,5-抗-2(E)-1,5-二醇，这将作为A-B和C-D螺旋酮的前体。提出了一种通过C（19）立体中心反转立体控制合成C- d螺旋酮的方法。(5) Apoptolidin的全合成。α -烷氧基酮的片段组装醛醇反应将用于合成apoptolidin的C(12)-C（28）片段。(6)氨苯二酚的全合成双功能烯基硼烷将用于两个醛的会聚偶联，生成1,5 -syn- p5 -2(Z)- 1,5 -二醇，这些二醇将作为合成两苯胺醇3的四氢吡喃单元的关键中间体。该方法也为胞霉素C二氢吡喃核的合成提供了一种替代策略。

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.