ACYCLIC DIASTEREOSELECTION: METHODOLOGY AND SYNTHESIS

描述(申请人提供)：我们建议继续我们在非环非对映选择性合成领域的研究，重点是开发新型的烯丙基金属试剂，应用于立体化学复杂的天然产物的全合成。下一批资助期的具体目标是： (1)利用3-BoryI取代的烯丙基硼烷开发新的合成方法。通过合成(Z)-双硼试剂80，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。将这一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的交叉歧化反应完成。 (2)Reidispongiolide A的全合成Reidispongiolide A是一种结构新颖的海洋来源的天然产物，对多种人类癌细胞具有显著的细胞毒性。通过1，3-双硼基试剂37和100的高度立体选择性的双烯丙基硼化反应进行片断组装，将开发出一种全合成雷公藤内酯A的路线。 (3)四纤维蛋白的全合成。Tetrafiicin是一种结构上很有趣的纤维蛋白原受体拮抗剂。使用1，3-双硼基试剂37、80和100进行片段组装，将开发一种非常简单和高度立体控制的该分子的合成。 (4)完成海洋来源的抗真菌药物安非比诺的全合成3.在下一个授权期内，将完成海源性抗真菌药安非比诺3的全合成。安息香醇中的多个1，5-二醇单元为上一批赠款期间高立体选择性1，5-二醇合成的发展提供了刺激。该技术还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)山梨内酯及其类似物的全合成。由于其具有诱导转化细胞系凋亡的能力，故对其有相当大的兴趣。将完成凋亡素的全合成。一种改进的C(12)-C(28)片段的第二代合成将通过我们的1，3-双硼基试剂用于片段组装的路线来开发。还将制备一系列凋亡素类似物进行生物学评价。

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.