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Microwave-enhanced liquid-phase synthesis of thiohydantoins and thioxotetrahydropyrimidinones

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Abstract

An efficient, microwave-assisted method for the liquid-phase combinatorial synthesis of 3,5-disubstituted thiohydantoins and 3,5-disubstituted 2-thioxotetrahydropyrimidin-4-ones has been developed. In synthesizing thiohydantoins, Fmoc-protected amino acids were coupled with polymer support and then deprotected to give primary amines. While in synthesizing thioxotetrahydropyrimidinones, 3-chloropropionyl chloride was immobilized to the support and subsequently reacted with various amines to form secondary amines. The PEG bound primary/secondary amines then were incorporated with various isothiocyanates to give thiourea intermediates and concomitant cyclization/cleavage steps occurred under mild basic condition. The desired products were then liberated from the soluble matrix in good yield and purity. All reactions described here were performed under microwave irradiation.

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Authors and Affiliations

  1. Laboratory of Combinatorial Drug Discovery, Department of Chemistry, National Dong Hwa University, Shou-Feng, Hualien-, 974, Taiwan

    Wen-Ben Yeh, Mei-Jung Lin, Ming-Juan Lee & Chung-Ming Sun

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  1. Wen-Ben Yeh
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  2. Mei-Jung Lin
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  3. Ming-Juan Lee
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  4. Chung-Ming Sun
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Correspondence to Chung-Ming Sun.

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Yeh, WB., Lin, MJ., Lee, MJ. et al. Microwave-enhanced liquid-phase synthesis of thiohydantoins and thioxotetrahydropyrimidinones. Mol Divers 7, 185–198 (2003). https://doi.org/10.1023/B:MODI.0000006802.21361.29

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  • DOI: https://doi.org/10.1023/B:MODI.0000006802.21361.29

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