ACYCLIC DIASTEREOSELECTION: METHODOLOGY AND SYNTHESIS

无环非对映选择：方法和合成

• 批准号: 6351182
• 负责人: WILLIAM R ROUSH
• 金额: $ 23.15万
• 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/6351182
• 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.

我们建议继续我们在非环非对映选择性合成领域的研究，重点是新的烯丙基金属化反应和片段组装Aldol反应，这些反应将在结构复杂、具有生物活性的天然产物的全合成的背景下开发。下一个授权期的具体目标是：(1)完成泰丹尼德的全合成。拟议综合的关键步骤已在前一批赠款期间成功模拟，从而确定了完成全面综合将采取的战略。(2)氧离子的烯丙化反应；单胞菌素C吡喃核的合成。基于烯丙基硅烷与氧离子的反应和闭环复分解反应，开发了一种合成单胞菌素C的2，6-反式二氢吡喃单元的新方法。(3)完成了链霉素C的全合成。关键片段组装Aldol步骤已在前一个授权期成功建模。(4)海绵抑素的全合成1.E-F双-吡喃单元的合成在前一授权期内完成。在即将到来的赠款期间，研究将集中在两个醛的收敛偶联生成L，5-抗戊二烯-2(E)-1，5-二醇的双官能团的伽马-硅烯丙基硼烷，它们将作为A-B和C-D螺酮的前体。还将开发一种通过倒置C(L9)立体中心来立体控制合成C-D螺酮的策略。(5)蜂毒内酯的全合成。α-烷氧基酮的片断组装Aldol反应将用于合成凋亡素的C(12)-C(28)片段。(6)双官能团烯丙基硼烷的全合成3.双官能团烯丙基硼烷用于两种醛的收敛偶联生成L，5-合成-2(Z)-L，5-二醇，这些化合物将作为合成苯并吡喃3的四氢吡喃单元的关键中间体。该方法也为合成花环霉素C二氢吡喃核提供了一种替代的策略。