Fluorous parallel synthesis of a hydantoin/thiohydantoin library.
Fluorous tagging strategy is applied to solution-phase parallel synthesis of a library containing hydantoin and thiohydantoin analogs. Two perfluoroalkyl (Rf)-tagged alpha-amino esters each react with six aromatic aldehydes under reductive amination conditions. Twelve amino esters then each react with 10 isocyanates and isothiocyanates in parallel. The resulting 120 ureas and thioureas undergo spontaneous cyclization to form the corresponding hydantoins and thiohydantoins. The intermediate and final product purifications are performed with solid-phase extraction (SPE) over FluoroFlash cartridges, no chromatography is required. Using standard instruments and straightforward SPE technique, one chemist accomplished the 120-member library synthesis in less than five working days, including starting material synthesis and product analysis.
Lu
Yimin
Y
Fluorous Technologies, Inc., University of Pittsburgh Applied Research Center, Pittsburgh, PA, USA.
Zhang
Wei
W
D000447:Aldehydes; D004952:Esters; D005466:Fluorocarbons; D006827:Hydantoins / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D017879:Isothiocyanates; D009682:Magnetic Resonance Spectroscopy; D013867:Thiohydantoins / Q000138:chemical synthesis*
D000447:Aldehydes; D004952:Esters; D005466:Fluorocarbons; D006827:Hydantoins; D007202:Indicators and Reagents; D017879:Isothiocyanates; D013867:Thiohydantoins