A convergent approach toward fidaxomicin: Syntheses of the fully glycosylated northern and southern fragments

Photolytic Studies on the Generation and Trapping of 6‐Oxomethylidenecyclohexa‐2,4‐diene‐1‐one Derivatives with Various Nucleophiles

“…This process is reversible and would relax back to the ground state S 0 . On the other hand, cleavage of this would again produce the acyl‐radical T 1 or its enol form T 1 e. This pathway may not be relevant for unsubstituted (or vinyl substituted) [15,33] resorcylates but may be critical here and for substituents used by De Brabander [18–20,34] …”

“… [1–14] A specific variation of α‐oxo‐ketenes are derivatives of 6‐oxomethylidenecyclohexa‐2,4‐dien‐1‐one ( 5 ), commonly prepared from benzodioxinone‐protected resorcylic acid derivatives [15–20] . Due to their potent reactivity, such as their high re‐aromatization potential, these functionalized ketenes have found use in natural product syntheses as well as in material science and polymer chemistry [1,4,18–34] . Tidwell reported IR spectroscopic evidence for the presence of 6‐oxomethylidenecyclohexa‐2,4‐dien‐1‐one derivatives such as 5 (ν max 2135 cm −1 ), through room temperature laser flash photolysis of benzodioxinones in acetonitrile solution, [15] while others reported on the existence of 5 by means of flash‐vacuum thermolysis of benzodioxinones in argon‐matrices at 600 °C [16] .…”

Total Synthesis of Tiacumicin B: Study of the Challenging β‐Selective Glycosylations**

“…Note that recently De Brabander used similar glycosylation strategies for the synthesis of the northern and southern glycosylated fragments of Tcn-B. 18 The total syntheses of tiacumicin A 19 , mangrolide A 20 and D, 21 three congeners of tiacumicin B with a slightly simplified aglycone structure were also achieved.…”

“…After assembly and cyclization of the aglycone, the rhamnosylation was carried out on the macrolide with an acetimidate glycosyl donor delivering the fully protected Tcn‐B (α/β: 1:4, 62 %). Note that recently De Brabander used similar glycosylation strategies for the synthesis of the northern and southern glycosylated fragments of Tcn‐B [19] . The total syntheses of tiacumicin A, [20] mangrolide A [21] and D, [22] three congeners of tiacumicin B with a slightly simplified aglycone structure were also achieved.…”

Beyond the approved: target sites and inhibitors of bacterial RNA polymerase from bacteria and fungi

“…283,284 Furthermore, a exible synthetic pathway for key intermediates was developed, enabling the future development of analogs with superior pharmacokinetics. 285 As current supplies of FDX originate as fermentation products of Dactylosporangium aurantiacum, additional optimizations of fermentation have also been reported. Intriguingly, the dehalogenated derivatives have improved activity proles against non-C. difficile pathogens as has been shown via knockout of the halogenase TiaM, which is responsible for the sequential chlorinations at C-4 00 and C-6 00 of the aryl ring.…”