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

Wong-Jin Chang; Kaushik Chanda; Chung-Ming Sun

doi:10.1071/CH08334

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

Wong-Jin Chang ^A , Kaushik Chanda ^A and Chung-Ming Sun ^A ^B

+ Author Affiliations

- Author Affiliations

^A Laboratory of Combinatorial Drug Discovery, Department of Applied Chemistry, National Chiao Tung University, Hsinchu 300-10, Taiwan.

^B Corresponding author. Email: cmsun@mail.nctu.edu.tw

Australian Journal of Chemistry 62(1) 42-50 https://doi.org/10.1071/CH08334
Submitted: 6 August 2008 Accepted: 30 October 2008 Published: 21 January 2009

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-β-carbolines on the support. Subsequently immobilized tetrahydro-β-carboline underwent a highly efficient intramolecular N-heterocyclization in a traceless fashion from various in-situ generated α-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.

Acknowledgement

The authors thank the National Science Council of Taiwan for the financial assistance and the authorities of the National Chiao Tung University for providing the laboratory facilities. We are grateful to the National Center for High-performance computing for computer time and facilities.

References

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

Abstract

Acknowledgement

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