Efficient Synthesis of ۵,۵-Disubstituted Bis-hydantoins/spirohydantoins and a Tetrakis-analogue: A Drug-like Multi-cyclic Scaffold

An easy method was developed for the efficient preparation of diversely new ۵,۵-disubstituted N(۳),N'(۳)-linkaged bis-hydantoins. At first, using the same methods, some ketones and terephthalaldehyde were converted to several hydantoins and a new bis-hydantoin , respectively. Then ۱,۶-dibromohexane, as a mild reagent, was employed for the alkylation and incorporation of synthesized substrates to produce quantitative yields of the desired bis-hydantoins. A tetrakis-hydantoin including four effective heterocyclic rings was also surprisingly synthesized from ۵,۵'-(۱,۴-phenylene)bis(imidazolidine-۲,۴-dione). The aim of this study is to synthesis of bis- and tetra core-hydantoins, bis-drug-like molecules employing a practical and reliable reaction process that requires slight amount of reagents; a process that is simple, accessible producing remarkable yields from an easy procedure that is cost effective and/or environmentally friendly. The resultant hydantoins potentially have bis- or multi-drugs behaviors in comparison with mono-counterparts, as cited in literatures for similar heterocyclic compounds. Spectral analysis confirmed the structures of the synthesized hydantoins.

کلیدواژه ها:

Spirohydantoin ، Bis-hydantoin ، Imidazolidine-۲ ، ۴-dione ، N(۳) ، N'(۳)-hexamethylene-bis-hydantoin ، Antiepileptic ، Bis-drug