New methods for preparation of tailor-made fluorine-containing compounds are in extremely high demand in nearly every sector of chemical industry. The asymmetric construction of quaternary C–F stereogenic centers is the most synthetically challenging and, consequently, the least developed area of research. As a reflection of this apparent methodological deficit, pharmaceutical drugs featuring C–F stereogenic centers constitute less than 1% of all fluorine-containing medicines currently on the market or in clinical development. Here we provide a comprehensive review of current research activity in this area, including such general directions as asymmetric electrophilic fluorination via organocatalytic and transition-metal catalyzed reactions, asymmetric elaboration of fluorine-containing substrates via alkylations, Mannich, Michael, and aldol additions, cross-coupling reactions, and biocatalytic approaches.

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Modern Approaches for Asymmetric Construction of Carbon–Fluorine Quaternary Stereogenic Centers: Synthetic Challenges and Pharmaceutical Needs

Since antibiotic resistance usually affords a gain of function, there is an associated biological cost resulting in a loss of fitness of the bacterial host. Considering that antibiotic resistance is most often only transiently advantageous to bacteria, an efficient and elegant way for them to escape the lethal action of drugs is the alteration of resistance gene expression. It appears that expression of bacterial resistance to antibiotics is frequently regulated, which indicates that modulation of gene expression probably reflects a good compromise between energy saving and adjustment to a rapidly evolving environment. Modulation of gene expression can occur at the transcriptional or translational level following mutations or the movement of mobile genetic elements and may involve induction by the antibiotic. In the latter case, the antibiotic can have a triple activity: as an antibacterial agent, as an inducer of resistance to itself, and as an inducer of the dissemination of resistance determinants. We will review certain mechanisms, all reversible, that bacteria have elaborated to achieve antibiotic resistance by the fine-tuning of the expression of genetic information.

Modes and Modulations of Antibiotic Resistance Gene Expression

Fifteen-Year Study of the Changing Epidemiology of Methicillin-Resistant Staphylococcus aureus

Background Methicillin-resisant Staphylococcus aureus (MRSA), a well-known nosocomial pathogen, is now emerging as a prominent cause of community acquired infections. We have noted an increase in number of cutaneous infections in Los Angeles over the past 2 years. The objective of the current study is to evaluate the clinical presentation and treatment of community acquired MRSA skin infections. Methods A retrospective chart review of 39 patients with 46 involved sites was performed. The sites of infection, morphology, antimicrobial susceptibility, and definitive treatment were evaluated. Results Cutaneous abscesses were the most common presentation of cutaneous MRSA infection. Definitive treatment consisted of incision and drainage in combination with antimicrobial therapy. The most effective antibiotics were vancomycin, trimethoprim/sulfamethoxazole in combination with rifampin, and linezolid. Conclusion Community acquired MRSA infection appears to be a growing problem requiring prompt diagnosis and treatment. First line treatment is incision and drainage in combination with linezolid, vancomycin, or combination trimethoprim/sulfamethoxazole and rifampin.

Community-acquired methicillin-resistant Staphylococcus aureus skin infection: a retrospective analysis of clinical presentation and treatment of a local outbreak.

Community methicillin-resistant Staphylococcus aureus (CMRSA) strains are being isolated with increasing frequency around the world. In Western Australia CMRSA are endemic in geographically remote communities and have been found to belong to five different contour-clamped homogeneous electric field (CHEF) electrophoretic patterns. Representatives of each of these CHEF patterns have been compared to CMRSA representative of CHEF patterns from other Australian states and New Zealand. With one exception, all of the isolates were nonmultiresistant and were not resistant to many antimicrobial agents other than the β-lactams. With one exception, which is not believed to be a CMRSA, all of the isolates harbored a β-lactamase plasmid. Erythromycin resistance was associated with a 2-kb plasmid. One of the β-lactamase plasmids was found to be able to acquire additional resistance determinants to become a multiple resistance plasmid. There were 10 multilocus sequence types belonging to eight distantly related clonal complexes of S. aureus. One new sequence type was found. Although most of the CMRSA harbored the type IVa SCCmec, a type IV structural variant was found and two new SCCmec types were identified. Protein A gene (spa) typing revealed two new spa types and, with two exceptions, corresponded to multilocus sequence typing. In contrast to other reports on CMRSA, most of the CMRSA strains studied here did not contain the Panton-Valentine leukocidin genes. The results also demonstrate that nonmultiresistant hospital strains such as UK EMRSA-15 may be able to circulate in the community and could be mistaken for CMRSA based on their resistance profiles.

Diversity among community isolates of methicillin-resistant Staphylococcus aureus in Australia.

Antimicrobial susceptibility and molecular characterization of community-acquired methicillin-resistant Staphylococcus aureus.

Synthesis and SAR evaluation of oxadiazolopyrazines as selective Haemophilus influenzae antibacterial agents.

Synthesis and antibacterial activity of 6-O-arylpropargyl-9-oxime-11,12-carbamate ketolides.

Synthesis and antibacterial activity of 5-methoxy- and 5-hydroxy-6-fluoro-1,8-naphthyridone-3-carboxylic acid derivatives.

A series of novel 6-O-arylpropargyl-9-oxime-ketolides was synthesized and evaluated against various pathogens. These new compounds show promising in vitro antibacterial potency and in vivo efficacy against macrolide resistant strains.

Mai H. Bui

Papers

Antimicrobial susceptibility and molecular characterization of community-acquired methicillin-resistant Staphylococcus aureus.

Synthesis and SAR evaluation of oxadiazolopyrazines as selective Haemophilus influenzae antibacterial agents.

Synthesis and antibacterial activity of 6-O-arylpropargyl-9-oxime-11,12-carbamate ketolides.

Synthesis and antibacterial activity of 5-methoxy- and 5-hydroxy-6-fluoro-1,8-naphthyridone-3-carboxylic acid derivatives.

Synthesis and Antibacterial Activity of 6-O-Arylpropargyl-9-oxime-11,12-carbamate Ketolides.