Microwave-Assisted Synthesis of Tetracyclic 2,5-Diketopiperazines on a Soluble Polymer Support: A Structural Analogue of Tadalafil

Abstract

Structural analogues of tadalafil that contain two diversity points have been synthesized from a soluble polymer support employing a Pictet-Spengler reaction using focussed microwave irradiation. Polymer-bound deprotected tryptophan reacts with various aldehydes to generate the tetrahydro-beta-carbolines on the support. Subsequently immobilized tetrahydro-beta-carboline underwent a highly efficient intramolecular N-heterocyclization in a traceless fashion from various in-situ generated alpha-alkyl and heteroalkyl amides in two steps to generate tetracyclic 2,5-diketopiperazines in high purity. All the compounds were isolated as cis and trans isomers with good yields.