Cascade N-Alkylation/Hemiacetalization for Facile Construction of the Spiroketal Skeleton of Acortatarin Alkaloids with Therapeutic Potentiality in Diabetic Nephropathy

Abstract

The concise building of the spiroketal core of acortatarin-type alkaloids as potential therapeutic agents in diabetic nephropathy was established in four steps, through a tandem N-alkylation/hemiacetalization between pyrrole units and the corresponding halo alcohols generated by convenient halomethylation of chiral lactones from natural aldoses. Graphical Abstract: The Acortatarin alkaloids exhibit a promising perspective against diabetic nephropathy and other ROS-linked diseases. Facile construction of the dioxaspirocycle motif was realized through tandem N-alkylation/hemiacetalization between pyrrole units and the corresponding halo alcohols, which were derived in turn from convenient halomethylation of chiral lactones in natural carbohydrates pool.[Figure not available: see fulltext.].