Vancomycin intermediate Staphylococcus aureus

Recently, the piperazine intermediate 15 for the total synthesis of (—)-lemon-omycin (9) was reported by Fukuyama et al. [14], (—)-Lemonomycin possesses interesting antibiotic activity against methiciUin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium, as well as cytotoxicity against the human colon tumor cell line HCT-116 [15]. The reaction of 2-isocyanoethyl phenyl carbonate 11 gave Ugi product 14, which was further transformed to a piperazine intermediate 15 (Scheme 2). 

Staphylococcus aureus is one of the major resistant pathogens. Found on the mucous membranes and the skin of around a third of the population, it is extremely adaptable to antibiotic pressure. MRS A was first detected in the early 1960s and is now quite common in hospitals. Strains with intermediate (4-8 J,g/ml) levels of resistance, termed glycopeptide intermediate Staphylococcus aureus (GISA) or vancomycin intermediate Staphylococcus aureus (VISA), began appearing in the late 1990s the first documented strain with complete (> 16 ag/ml) resistance to vancomycin, termed vancomycin-resistant Staphylococcus aureus (VRSA), appeared in 2002. 

Aeschlimann JR, Allen GP, Hershberger E, Rybak MJ. Activities of LY333328 and vancomycin administered alone or in combination with gentamicin against three strains of vancomycin-intermediate Staphylococcus aureus in an in vitro pharamacodynamic infection model. Antimicrob Agents Chemother 2000 44 2991-2998. 

The most relevant of the coagulase-positive species is Staphylococcus aureus subsp. aureus (further S. aureus), pathogenic to both humans and animals. It is an extraordinary versatile pathogen and the major causative agent of numerous hospital-and community acqnired infections. The spread, survival and prevalence of antibiotic resistant clones of S. aureus are immensely important problems for human health. Major antibiotic resistance problems are typically associated with methicillin (oxacillin) resistant S. aureus strains (MRSA) and, more recently, vancomycin-intermediate (VISA) and vancomycin-resistant (VRSA) strains. Up to 30% of the hnman population carries S. aureus without any symptoms. In most cases, however, the colonizing strain serves as an endogenous reservoir for clinical infections (von Eiff et al. 2004). The disease spectrum includes abscesses, bacteremia, central nervons... 

Hanaki, H., Hososaka, Y, Yanagisawa, C., Otsuka, Y, Nagasawa, Z., Nakae, T, Suna-kawa, K. Occurrence of vancomycin-intermediate-resistant Staphylococcus aureus in Japan. J Infection Chemoth. 2007, 13(2), 118-121. 

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