Full Paper Synthesis and Antimicrobial Activities of a Novel Series of Heterocyclic a-Aminophosphonates Mohamed F. Abdel-Megeed 1 , Badr E. Badr 2 , Mohamed M. Azaam 1 , and Gamal A. El-Hiti 1,3 1 Faculty of Science, Department of Chemistry, Tanta University, Tanta, Egypt 2 Faculty of Science, Department of Botany, Tanta University, Tanta, Egypt 3 School of Chemistry, Cardiff University, Cardiff, UK Two series of novel a-aminophosphonates having heterocyclic moieties were synthesized in high yields. The structures of the newly synthesized compounds were confirmed by their elemental analyses, IR, 1 H NMR and MS spectral data. These compounds were screened for their antibacterial activities against Escherichia coli (NCIM2065) as a Gram-negative bacterium, Bacillus subtilis (PC1219) and Staphylococcus aureus (ATCC25292) as Gram-positive bacteria, and Candida albicans and Saccharomyces cerevisiae as fungi. The minimum inhibitory concentrations (MICs) of the synthesized compounds show high antibacterial and antifungal activities at low concentrations (10–1000 mg/mL). Furthermore, their lethal doses indicated that such compounds are safe for use as antimicrobial agents. Keywords: a-Aminophosphonates / 2-Amino-4-chloro-6-methylpyrimidine / 3-Aminoquinazolin-4(3H)-one / Antimicrobial activities / Lethal dose Received: March 18, 2012; Revised: June 3, 2012; Accepted: June 19, 2012 DOI 10.1002/ardp.201200109 Introduction a-Aminophosphonates are among the most common and biologically active organophosphorus compounds [1–3]. a-Aminophosphonates and in particular the ones having heterocyclic moieties show very interesting biological activities and have been used as peptide mimics, inhibitors of serine hydrolase, enzyme inhibitors, antibiotics, anti- bacterial, antifungal, anticancer, anti-HIV and herbicidal agents [4–20]. Various synthetic processes have been developed for the production of a-aminophosphonates [21–27]. However, the most efficient method involves the one-pot Mannich-type [28] process of carbonyl compounds, amines and diphenyl phosphite in the presence of a Lewis acid catalyst. Such process is simple, general, high yielding and accommodates various substituents into aminophosphonates [29–32]. We have previously reported efficient syntheses of various biologically active heterocyclic compounds [33–40] as part of our continuing interest in organic synthesis. Recently, we have reported the successful synthesis, antimicrobial and anticancer activities of a novel series of a-aminophospho- nates [41]. The present work was aimed to synthesize novel a-aminophosphonates containing quinazolin-4(3H)-one and pyrimidine moieties with the hope that new antimicrobial agents could be developed. We now report the successful synthesis of a range of a-aminophosphonates and their anti- microbial activities against Gram-negative and Gram-positive bacteria and fungi. Results and discussion Chemistry Two series a-aminophosphonates were synthesized in which heterocyclic amines namely 3-aminoquinazolin-4(3H)-one (1) and 2-amino-4-chloro-6-methyl pyrimidine (2) were used. Reactions of 3-aminoquinazolin-4(3H)-one (1; 4 molar equiva- lents) with various aromatic aldehydes namely 2,4-dihydroxy- benzaldehyde, 4-chlorobenzaldehyde and 4-nitrobenzaldehyde (2 molar equivalents) and triphenylphosphite (3 molar equiv- alents) in the presence of lithium perchlorate as a Lewis acid catalyst in dichloromethane (DCM) at room temperature for 28–36 h gave the corresponding diphenyl (aryl)(4-oxoquina- zolin-3(4H)-ylamino)methylphosphonates 3–5 (Scheme 1) in 70–83% yields after crystallization from ethanol. Correspondence: Gamal A. El-Hiti, School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff CF10 3AT, UK. E-mail: el-hitiga@cardiff.ac.uk Fax: þ442920870600 Arch. Pharm. Chem. Life Sci. 2012, 000, 1–6 1 ß 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim