Efficient one-step synthesis of 4-amino substituted phthalimides and evaluation of their potential as fluorescent probes.

Tomas Kindahl, Erik Chorell

Organic & biomolecular chemistry 2014 Jul 7

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The phthalimide scaffold is recognized from bioactive compounds and marketed drugs, but can also be used as fluorescent probes by introducing a 4-amino substituent. Unfortunately, a general and convenient method to synthesize various 4-amino substituted phthalimides has been lacking. To overcome this, an atom efficient one-step synthesis of 4-amino substituted phthalimides in good to excellent yields that tolerate a wide range of substituents has been developed. Several of the generated compounds display interesting solvatochromic properties with high quantum yield of fluorescence in non-polar solvents that are significantly reduced in polar protic solvents. Many of these compounds displayed non-toxic properties and non-detectable unspecific binding and can thus potentially be linked to a substrate and used as fluorescent probes. Furthermore, bioactive and fluorescent 4-amino substituted phthalimides with IC50-values in the low micromolar range in cell-based assays have been identified and could be used to study uptake and distribution. The developed convenient synthetic method is thus valuable not only to construct fluorescent probes and fluorescent bioactive compounds to gain information about target binding, but also from a structure activity point of view in the various areas where the phthalimides have displayed activity.

Citation

Tomas Kindahl, Erik Chorell. Efficient one-step synthesis of 4-amino substituted phthalimides and evaluation of their potential as fluorescent probes. Organic & biomolecular chemistry. 2014 Jul 7;12(25):4461-70