engleski

Synthesis of enantiopure 3, 5-disubstituted hydantoins via transformation of β-lactam ureas

Hydantoins are an important class of heterocyclic compounds, and they can often be found as a structural motif in various drugs and natural compounds [1]. Hydantoin ring is found in biologically active marine alkaloids isolated from different marine organisms [2]. In addition, optically pure hydantoins are used as chiral auxiliaries in stereoselective synthesis and as metal ligands in catalysis [3]. In conducted research the 3, 5-disubstituted hydantoins are prepared from enantiomerically pure β-lactam ureas (Scheme 1). In the first step, enantiomerically pure trans-3-amino-β-lactams in reaction with structurally different isocyanates are converted into trans-3-amino-β-lactam ureas (up to 99% ee, and 90% yield). In the next step preparation of 5-substituted hydantoins is carried out by an intramolecular transformation of trans-3-amino-β-lactam ureas. The conversion is carried out in methanol in the presence of different bases (K2CO3, NaOMe, NaH). Special attention was paid to the stereochemistry during transformation of trans-3-amino-β-lactam ureas to corresponding hydantoins with respect to the 5-position of hydantoin on which racemization easily occur. The racemization is largely dependent on the reaction conditions. The advantage of the proposed method compared to the synthesis from derivatives of α-amino acids is ability to introduce an additional chiral center on the side chain, and the use of mild reaction conditions.

Hydantoins ; β-lactam ureas ; transformation

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