Macrolide antibiotics recent developments

Azithromycin. Azithromycin is another recently developed macrolide antibiotic. After oral administration on an empty stomach, azithromycin is rapidly absorbed and widely distributed throughout the body. Because azithromycin has an extended half-life, once-daily dosing is effective and encourages patient compliance. 

Macrolide antibiotics are administered orally, but many of them exhibit low and/or variable degrees of oral absorption, low serum concentrations, and short half-lives. Consequently, selection of semi-synthetic derivatives for development has often been guided by greater oral bioavailability, longer half-life, and higher and more prolonged concentrations in serum and tissues. The clinical pharmacokinetic parameters of several 16-membered macrolides have recently been reviewed [58, 233, 234],... 

Paterson, I., Mansuri, M. M. Recent developments in the total synthesis of macrolide antibiotics. Tetrahedron 1985,41, 3569-3624. 

Finally, a recent noteworthy development is the use of molecular mechanics calculations to rationalize and predict the stereoselective reduction of large-ring ketones. This has been of particular interest to chemists working on the synthesis of macrolide antibiotics. An example is the reduction of the cyclic oxolactone 3-methyl-2-oxa-l,7-cyclotetradecanedione with LS-Se-leetride or L-Selectride to give the /ram-alcohol with d.r. (transjcis) 90 10131. 

Kirst, H. A. (1998). Recent developments with macrolide antibiotics. Exp. Opin. Then Patients 8, 111-120. 

A number of new macrolide antibiotics with interesting bioactivity have been isolated, and the unique and complex structures have been determined. Toward the total synthesis of such attractive macrolide antibiotics, very efficient synthetic strategies and useful methodologies have been developed. Recent advances in macrolide synthesis based on newly developed strategies and methodologies are remarkable various complex macrolides having many chiral centers have been efficiently synthesized with excellent stereoselectivity. Recently, combinatorial... 

In this chapter, the molecular-biological mode of action of macrolide antibiotics and the biochemical and genetic mechanisms of resistance to MLS antibiotics are reviewed. Based on a recent X-ray crystallographic study on a 50S ribosomal subunit from Haloarcula marismortui and the finding of intracellular macrolide accumulation, the mode of action from the viewpoint of a new hypothetical concept, deposition binding, and mechanisms of drug resistance in clinically isolated bacteria are discussed. In addition, recent major developments in macrolide antibiotics are briefly described. 

I. Paterson and M.M. Mansuri, Recent Developments in the Total Synthesis of Macrolide Antibiotics, Tetrahedron, 1985, , 3569. 

Present studies at IFR are concerned with the development of methods for examining potential complex formation with purified cyclosophorans. Preliminary studies have been carried out on the macrolide antibiotic Amphotericin B (AmB). This material is a potent systemic fungicide but its considerable toxicity and poor solubility have restricted its therapeutic applications. Attempts to improve water solubility, and thus lessen the aggregation of AmB, by derivatization have resulted in decreasing activity. Recently it has been reported that AmB can be solubilized by complexation with 7"cyclodextran and that the complex retains the full anti-fungal activity. 4 ... 

A highly effective method for the construction of macrolactone ring ii is the intramolecular lactonization of the corresponding seco-acid i (Fig. 2). Thus, various effective methods for the synthesis of macrolactones were developed during the 1970s and 1980s and have been successfully apphed to the total synthesis of macroUde antibiotics. In the 1990s, new methods for macrolactonization were reported [35] however, they have not yet been applied frequently to macrolide synthesis. Thus, in this section, the established methods applied to macrolide synthesis are introduced, and selected recent applications are shown in Scheme 12 and Section III.F. 

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