Fluorinated erythronolides

The microbial glycosidation of (8S)-8-fluoro erythronolides were investigated by the same research group. Fluorinated erythronolides A (46) and B (47) were added into the fermentation broth of Streptomyces erythraeus ATCC 31772, a blocked mutant in EM biosynthesis (Scheme 6). In this procedure, (85 )-8-fluoro... 

Erythromycins are macrolide antibiotics produced by bacterial fermentation. Fluoiination of erythromycin has been studied as a strategy to insure better stability in acidic medium and/or to achieve better bioavailability. An erythromycin, fluorinated at C-8, flurithromycin, was launched several years ago. Its preparation involves an electrophilic fluorination, with CF3OF [119] or with an N-F reagent A/-fluorobenzenesulfonimide (NFSI) [120], of the 8,9-anhydroerythromy-cin-6,9-hemiacetal or of the erythronolide A (Fig. 44). 

Flurithromycin is an erythromycin fluorinated at C-8, which was launched several years ago (cf. Chapter 8). Its preparation involves an electrophilic fluorination with or with an N— F reagent (NFSI) of 8,9-anhydroerythromycin-6,9-hemiacetal or of erythronolide A. Glycosylations have also been performed by fermentation (Figure 4.57). ... 

Another successful approach for blocking the intramolecular decomposition illustrated in Fig. 2 involved inhibition of the dehydration step leading to the anhydrohemiketal by replacement of the C-8 proton of erythromycin with fluorine. Preparation of flurithromycin (8-fluoroerythromycin, see Fig. 4) has been achieved by both chemical and biochemical methods. Addition of 8(S)-8-fluoroerythronolide A to a mutant strain of Streptomyces erythreus blocked in biosynthesis of its endogenous lactone (erythronolide) yielded the desired fluorinated erythromycin [40]. This technique of mutasynthesis has been further employed for the production of other fluorinated derivatives of erythromycin [40, 41]. Fluorination of different 8,9-anhydro-6,9-hemiketal derivatives of erythromycin by chemical means with reagents such as trifluoromethyl hypo-fluorite or perchloryl fluoride (with subsequent reduction of the N-oxide) has also been reported [42, 43]. 

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