B-class streptogramins contain 19-membered depsipeptide (peptides with ester linkages) lactones; one example is quinupristin. Dalfopristin and quinupristin together comprise the antibiotic Synercid which was approved by the US FDA in 1999 for treating multidrug-resistant (MDR) skin infections, including those caused by vancomycin-resistant enterococci (VRE). Class A streptogramins bind to the 50S subunit of the bacterial ribosome at its peptidyltransferase center (PTC), while the class B streptogramins bind to the 50S subunit of 70S ribosome at the exit tunnel; 192 the binding of class B streptogramins to the bacterial ribosome is increased in the presence of the class streptogramins so that the combination of class A and B streptogramins is bactericidal while class A or B streptogramins alone are bacteriostatic. Inhibition of the bacterial ribosome prevents protein synthesis and thus kills bacteria. Streptogramins are useful against aerobic Gramnegative and Gram-positive bacteria such as vancomycin-or multidrug-resistant Enterococcus faecium (not faecalis), Resistance to the streptogramins class of antibiotics is difficult, as the PTC is highly conserved and tolerates minimal alterations. Export of streptogramin antibiotics from bacterial cells occurs through transporters encoded by genes such as lsa(E). In addition, O-methylation of A2503 in the bacterial ribosome blocks the binding of antibiotics to the PTC and thus reduces or negates inhibition. In addition, acetylation of A2503 with virginiamycin acetyltransferases also reduces streptogramin antibiotic activity. Other mechanisms include the presence of efflux pumps. While the use of streptogramins is limited, the development of synthetic methods and the modularity of their structures makes them accessible to chemical synthesis which allows significant modification of the cores not available through semisynthesis. The Li and Seiple groups have developed analogs of streptogramins and the related lankacidins as potential antibiotic agents with expanded scope 191 , with the synthesis of streptogramins on up to 10g scale. For example, the replacement of the methyl group β to the ester oxygen in virginiamycin M2 with an allyl group and of the righthand ketone with a fluoromethylene moiety yields a highly active analog with improved activity against drug-resistant strains of Oxazolidinones: It is the class of antibiotics that inhibit protein synthesis. Two aryl-substituted oxazolidinones have been approved as antibacterial agents. Linezolid (R = MeCONH; R 1 = 4morpholinyl) was approved by the US FDA in 2000 for treating vancomycin-resistant Enterococcus faecium, drug-resistant and -susceptible Staphylococcus aureus and Streptococcus pneumoniae, Streptococcus agalactiae, and Streptococcus pyogenes. Tedizolid [R = HO; R 1 = 2-(5-tetrazolyl)-5-pyridinyl] phosphate ester (Supplementary Table ) was approved by the US FDA in 2014 for bacterial skin and skin-structure infections by Enterococcus faecalis, drug-resistant and -susceptible Staphylococcus aureus and Streptococcus pneumoniae, Streptococcus agalactiae, and the Streptococcus anginosus group. Oxazolidinones bind to the bacterial 50S ribosome subunit at the PTC, inhibiting protein synthesis by hindering the formation of initiation complex. Resistance to oxazolidinones is slow to develop but has been observed -O-methylation of A2503 in the 50S subunit of the bacterial ribosome (mediated by the methyltransferase Cfr) abrogates binding, as does the G2576T mutation in domain V of the 23S rRNA. Mutations in the genes rplC and rplD for the ribosomal proteins L3 and L4 also yield resistant bacterial phenotypes. The simplicity of oxazolidinones and the availability of arylnitrogen coupling reactions such as Buchwald-Hartwig coupling enables drug developers to rapidly generate analogs to circumvent bacterial resistance. Linezolid, however, has limited aqueous solubility, making its administration more difficult. In addition, reversible myelosuppression and irreversible optic and peripheral neuropathies are observed on long-term administration (six months or more) of linezolid, and it acts as an inhibitor of monoamine oxidases, making it incompatible with a variety of foods and drugs.