Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
J Am Chem Soc. 2010 Mar 10;132(9):3009-12. doi: 10.1021/ja908819q.
A total synthesis of the Aspidosperma alkaloids (+)-fendleridine and (+)-1-acetylaspidoalbidine is detailed, providing access to both enantiomers of the natural products and establishing their absolute configuration. Central to the synthetic approach is a powerful intramolecular [4+2]/[3+2] cycloaddition cascade of a 1,3,4-oxadiazole in which the pentacyclic skeleton and all the stereochemistry of the natural products are assembled in a reaction that forms three rings, four C-C bonds, and five stereogenic centers including three contiguous quaternary centers, and introduces the correct oxidation state at C19 in a single synthetic operation. The final tetrahydrofuran bridge is subsequently installed in one step, enlisting an intramolecular alcohol addition to an iminium ion generated by nitrogen-assisted opening of the cycloadduct oxido bridge, with a modification that permits release of useful functionality (a ketone) at the cleavage termini.
详细介绍了（+）-芬德勒碱和（+）-1-乙酰基阿比定碱的全合成，为两种天然产物的对映异构体提供了途径，并确定了它们的绝对构型。合成方法的核心是一种强大的 1,3,4-噁二唑的分子内[4+2]/[3+2]环加成级联反应，其中五元环骨架和天然产物的所有立体化学都在一个反应中组装，形成三个环、四个 C-C 键和五个立体中心，包括三个连续的季碳原子，并在单个合成操作中引入 C19 上的正确氧化态。最后一步安装四氢呋喃桥，通过氮辅助打开环加成物氧化桥生成的亚胺离子的分子内醇加成来完成，该方法进行了改进，可在断裂末端释放有用的功能（酮）。
