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Fluorous parallel synthesis of a hydantoin/thiohydantoin library

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Abstract

Fluorous tagging strategy is applied to solution-phase parallel synthesis of a library containing hydantoin and thiohydantoin analogs. Two perfluoroalkyl (Rf)-tagged α-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 FluoroFlashTM 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.

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Abbreviations

Rf:

perfluoroalkyl group

SPE:

solid-phase extraction

DIC:

1,3-diisopropylcarbodiimide

HOBT:

1-hydroxybenzotriazole

Fmoc:

9-fluorenylmethoxycarbonyl

Boc:

t-butoxycarbonyl

THF:

tetrahydrofuran

DMAP:

4-dimethylaminopyridine

DMF:

N,N-dimethylformamide

HPLC:

high-performance liquid chromatography

TLC:

thin-layer chromatography

MS:

mass spectrometry

NMR:

nuclear magnetic resonance spectroscopy

LC-MS:

liquid chromatography-mass spectrometry

FTI:

Fluorous Technologies, Inc.

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  1. Fluorous Technologies, Inc., University of Pittsburgh Applied Research Center, Pittsburgh, PA, U.S.A.

    Yimin Lu & Wei Zhang

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  1. Yimin Lu
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  2. Wei Zhang
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Correspondence to Wei Zhang.

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Lu, Y., Zhang, W. Fluorous parallel synthesis of a hydantoin/thiohydantoin library. Mol Divers 9, 91–98 (2005). https://doi.org/10.1007/s11030-005-1293-y

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  • DOI: https://doi.org/10.1007/s11030-005-1293-y

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