Nov-Dec 2007 Synthesis and Anti-Staphylococcal Activity of New Halogenated Pyrroles Related to Pyrrolomycins F 1407 Maria Valeria Raimondi*, Domenico Schillaci and Salvatore Petruso Dipartimento di Chimica e Tecnologie Farmaceutiche, Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy *Corresponding author. Tel. +39 091 6236115; fax +39 091 6236119, e-mail address: mvraimondi@unipa.it Received January 11, 2007 N H Br Br HO Cl O Br Cl 2 N H Br Cl Br HO Cl O Cl 3 N H Cl Br HO Cl O Br Cl N H Cl Cl HO Cl O Br Cl 4 5 The chemical synthesis of new halogenated pyrroles related to pyrrolomycins F is described and the anti-staphylococcal activity compared. The replacement of 4'-bromo atom of parent compounds with two chloro atoms at 3' and 5' position increase the antibacterial activity against a reference strain of S. aureus. J. Heterocyclic Chem., 44, 1407 (2007). INTRODUCTION Antibiotic resistance of important Gram-positive pathogens as Staphylococcus aureus , is currently a significant global health problem. The overuse of antibiotics, both in human and animal population, played an important role in the beginning of drug-resistant strains. Furthermore, bacteria can survive and thrive in hostile environments, forming, on living and nonliving surfaces, as indwelling medical devices, organized communities of bacterial cells (biofilms), that are difficult or impossible to treat with conventional antibiotics [1]. There is an urgent need to develop new agents against these pathogens and an interesting resource of new antibiotics is represented by some natural halogenated pyrroles, known as pyrrolomycins (Figure 1). Such molecules, isolated from culture broth of Actinosporangium vitaminophilum SF-2080 [2-5], have a good activity especially against Gram-positive bacteria, in particular Staphylococcus aureus. A different group of pyrrolomycins, generically named PM-F, has been produced from A. vitaminophilum SF- 2080 when bromide ion was added to the fermentation medium [6] (Figure 2). N H Br Br HO Br O Br PM-F 1 N H Br Cl Br HO Br O PM-F 2a N H Cl Br HO Br O Br N H Cl Cl HO Br O Br PM-F 2b PM-F 3 Figure 2 Some PM-F components possessed equal or more potent activity, against some Gram-positive bacteria, than N H Cl Cl NO 2 PMA N H Cl Cl NO 2 HO Cl Cl PMB N H Cl Cl HO Cl Cl O PMC N H Cl Cl Cl HO Cl Cl O PMD N H Cl NO 2 HO Cl Cl PME Figure 1