Organocatalytic Enantioselective Michael–Acetalization–Reduction–Nef Reaction for a One-Pot Entry to the Functionalized Aflatoxin System. Total Synthesis of (−)- Dihydroaflatoxin D2 and (−)- and (+)-Microminutinin

An efficient method has been developed for the enantioselective synthesis of the aflatoxin system with multiple stereocenters via a sequence of organocatalytic Michael–acetalization–reduction–Nef reactions that proceed with high enantioselectivities (90–99% ee). The one-pot reaction sequence provides a facile entry to the aflatoxin system, including dihydroaflatoxin D2, which includes a formal total synthesis of aflatoxin B2. The first total synthesis of (−)- and (+)-microminutinin was also achieved via this protocol.本研究开发了一种高效合成方法，通过有机催化迈克尔-缩醛化-还原-Nef反应序列，实现了含多手性中心的黄曲霉毒素体系的对映选择性合成，该反应序列的对映体过量值（enantiomeric excess，ee）可达90%~99%。该一锅法反应序列可便捷合成黄曲霉毒素体系相关产物，包括二氢黄曲霉毒素D2（dihydroaflatoxin D2），并完成了黄曲霉毒素B2（aflatoxin B2）的形式全合成。此外，依托该合成策略，本研究还首次实现了左旋(-)-和右旋(+)-微小菌素（microminutinin）的全合成。