Microwave-assisted polymer-supported combinatorial synthesis.

Lead identification and optimization is always a challenge to the medicinal chemists in drug discovery. Numbers of simple to complex and smaller to bigger organic compounds are prepared to meet the screening purpose of biological targets. Conventional solution phase synthetic methodologies are lacking the speed to run along with the need of medicinally interesting compounds due to their long reaction time, tedious work-up and purification problems. Alternatively opted polymer-supported synthesis of combinatorial libraries has been emerged as a promising tool in generating large numbers of structurally diverse molecules in a manner rapid and parallel. Microwave-assisted solid/liquid phase combinatorial synthetic techniques have been proved efficient in reducing the reaction time from days & hours to minutes & seconds and more promisingly to produce improved yields with high purities. This review briefs about the theory behind microwave chemical technology and glimpses of recent advancements in its application on polymer supported combinatorial synthesis.

Traceless liquid phase synthesis of piperazinediones.

Liquid phase combinatorial synthesis (LPCS) of piperazinediones by the use of soluble polymer support is explored to generate libraries. Proline anchored polyethylene glycol monomethyl ether (PEG) underwent dipeptide formation with different Fmoc-amino acids in the presence of dicyclohexyl carbodiimide (DCC). Deprotection of Fmoc accompanied with the cleavage from polymer support with cyclization of dipeptide to piperazinediones offers a facile and effective way to prepare diverse combinatorial libraries. Excellent yields and purities were achieved by simple wash and precipitation method.

Microwave-enhanced liquid-phase synthesis of thiohydantoins and thioxotetrahydropyrimidinones.

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.