Solid-Phase Synthesis of Tetrahydroβ-carboline Alkaloid

Significance

The solid-phase synthesis of tetrahydro-β-carboline alkaloid via intramolecular Pictet-Spengler cyclization was demonstrated. FmocTrp-loaded resin 2 was prepared from resin 1 and Fmoc-Trp(Boc)-OH. Resin-supported peptides 3 were prepared from 12 different amino acids and Trp-loaded resin 2 using CID, HOBt and DIPEA as coupling reagents. After Fmoc deprotection of dipeptides 3 on solid supports, dimethoxy­acetaldehyde was condensed with dipeptides. The resulting secondary amines were treated with eight different isocyanates in the presence of DIPEA to give acetals 4 bearing urea groups. Treatment of 4 with HCOOH promoted resin cleavage, deprotection, and the Pictet-Spengler cyclization via intra-molecular formation of acyliminium species in one step to afford the desired tetrahydro-β-carboline alkaloids.