Preparation of pilot library with tetrahydro-β-carboline alkaloid core skeleton using tandem intramolecular Pictet–Spengler cyclization

A solid phase strategy has been developed for the synthesis of tetrahydro-β-carboline alkaloid library. The key transformation is an acid-catalyzed tandem intramolecular Pictet–Spengler cyclization from l-tryptophan which forms acyl iminiums with synchronous cleavage of products from the acid-labile SASRIN™ solid support. A pilot library with two diversity points has been successfully synthesized in high purity to demonstrate this strategy.