Studies toward the total synthesis of marine natural products having an azaspiro ring system

针对具有叠氮环体系的海洋天然产物螺内酯类化合物的全合成，探索了这些分子的E环和BCD环体系的构建。以l -谷氨酸为原料制备的二烯与7元α-亚甲基内酯的Diels-Alder反应具有完全的区域选择性和适度的外显面和非对映面选择性，可得到所需的外显面环加合物为主要产物。由于所有试图通过串联双半晶形成/杂环michael加成序列从无环前体获得所需的双二酮异构体的尝试都失败了，我们将注意力转向跨环反应，并设计和合成了一个大环底物。

Toward the total synthesis of spirolides, marine natural products with an azaspirocyclic system, the construction of E and BCD ring systems of these molecules have been explored. Diels-Alder reaction of the diene, prepared from L-glutamic acid, with a 7-membered α-methylene lactone exhibited complete regioselectivity and modest exo and diastereoface selectivity to provide the desired exo cycloadduct as the major product. Since all attempts to obtain the desired dispiroketal isomer from an acyclic precursor by tandem double hemiketal formation/hetero-Michael addition sequence met with failure, we turned our attention to the transannular reaction, and designed and synthesized a macrocyclic substrate.