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Synthesis, chiral separation and biology activity of (±)-trans-β-lactam ureas

β‐Lactams are of utmost importance in medicine owing to their broad range of bioactivities.1 They are well-known antibiotics, but also possess other pharmacological activities, such as human cytomegalovirus protease inhibitors, LHRH antagonists, cholesterol absorption inhibitors, anticancer agents, antihyperglycemic, antimalarial, anti-HIV, anti-inflammatory and analgetic activities.2, 3 Apart from their pharmacological purposes, β‐lactams are also valuable from a synthetic point of view as building blocks for the synthesis of numerous biologically active natural compounds.1 In our study, the mixture of cis/trans-3- phthalimido-β-lactam 2a/b was prepared by Staudinger [2+2] ketene-imine cycloaddition (Scheme 1). In the next step, deprotection of the phthalimido group was carried out affording desired (±)-trans-3-amino-β-lactam 3, which was transformed into the (±)-trans-β-lactam ureas 5a-n with various alkyl and aryl isocyanates. The stereochemistry of this class of β-lactams has already been determined and remains unchanged during this conversion.3 The biological activities of the obtained derivatives have been characterized by using in vitro assays (antibacterial, antifungicide, toxicity) and modelling approaches (ADMET, SAR). Scheme.

β‐Lactams ; antibacterial ; antifungal ; ADME

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