ACYCLIC DIASTEREOSELECTION: METHODOLOGY AND SYNTHESIS

无环非对映选择：方法和合成

• 批准号: 7012171
• 负责人: WILLIAM R ROUSH
• 金额: $ 24.94万
• 依托单位: SCRIPPS FLORIDA
• 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 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7012171
• 关键词: allyl compound; antifungal agents; apoptosis; biological products; boranes; chemical synthesis; cytotoxicity; fibrinogen receptors; stereochemistry

DESCRIPTION (provided by applicant): We propose to continue our research in the area of acyclic diastereoselective synthesis, with emphasis on the development of novel allylmetal reagents for application to the total synthesis of stereochemically complex natural products. Specific goals for the next grant period are: (1) Development of New Synthetic Methodology Utilizing 3-BoryI-Substituted Allylboranes. The scope of double allylboration reactions for the highly stereocontrolled synthesis of 1,5-diol systems will be expanded by the synthesis of the (Z)-bisboryl reagent 80. Extensions of this methodology to the stereocontrolled synthesis of methyl branched 1,5-diol systems will be accomplished by cross metathesis reactions of allylboronates 84 and 98. (2) Total Synthesis of Reidispongiolide A. Reidispongiolide A is a structurally novel natural product of marine origin with significant cytotoxicity against various human cancer cell lines. A total synthesis of reidispongiolide A will be developed by a route featuring highly stereoselective double allylboration reactions of 1,3-bisboryl reagents 37 and 100 for fragment assembly. (3) Total Synthesis of Tetrafibricin. Tetrafibricin is a structurally interesting fibrinogen receptor antagonist. A very simple and highly stereocontrolled synthesis of this molecule will be developed using 1,3- bisboryl reagents 37, 80, and 100 for fragment assembly. (4) Completion of a Total Synthesis of Amphidinol 3. A total synthesis of amphidinol 3, an antifungal agent of marine origin, will be completed in the coming grant period. The multiple 1,5-diol units in amphidinol provided the stimulus for development of the highly stereoselective 1,5-diol synthesis in the preceding grant period. This technology will also play an important role in the synthesis of the two tetrahydropyran units in the natural product. (5) Total Synthesis of Apoptolidin and Apoptolidin Analogs. Apoptolidin is of considerable interest owing to its ability to induce apoptosis in transformed cell lines. A total synthesis of apoptolidin will be completed. An improved second-generation synthesis of the C(12)-C(28)fragment will be developed by a route featuring our 1,3-bisboryl reagents for fragment assembly. A series of apoptolidin analogs also will be prepared for biological evaluation.

描述（由申请人提供）：我们建议继续我们在非环状非对映选择性合成领域的研究，重点是开发新的烯丙基金属试剂，用于立体化学复杂的天然产物的全合成。下一个赠款期的具体目标是： (1)3-硼基取代烯丙基硼烷合成新方法的研究进展通过（Z）-双硼基试剂80的合成，将扩大用于高度立体控制合成1，5-二醇体系的双烯丙基硼化反应的范围。将该方法扩展到甲基支链1，5-二醇体系的立体控制合成将通过烯丙基硼酸酯84和98的交叉复分解反应来完成。 (2)雷地松素A的全合成ReidispongiA是一种结构新颖的海洋天然产物，对多种人类癌细胞系具有显著的细胞毒性。reidispongiplastin A的全合成将通过具有高度立体选择性的1，3-双硼基试剂37和100的双烯丙基硼化反应进行片段组装的路线开发。 (3)四环素的全合成四环素是一种结构有趣的纤维蛋白原受体拮抗剂。一个非常简单的和高度立体控制的合成这种分子将开发使用1，3- bisboryl试剂37，80，和100的片段组装。 (4)完成Amphidinol 3的全合成。海洋来源的抗真菌剂ampdinol 3的全合成将在下一个资助期内完成。amphidinol中的多个1，5-二醇单元为前一个资助期高度立体选择性的1，5-二醇合成的发展提供了刺激。该技术也将在天然产物中两个四氢吡喃单元的合成中发挥重要作用。 (5)Apoptolidin及其类似物的全合成。凋亡素由于其在转化细胞系中诱导凋亡的能力而引起相当大的兴趣。将完成apoptolidin的全合成。改进的第二代合成的C（12）-C（28）片段将开发的路线具有我们的1，3-bisboryl试剂片段组装。还将制备一系列雷公藤甲素类似物用于生物学评价。