846606-79-9Relevant academic research and scientific papers
A convergent approach toward fidaxomicin: Syntheses of the fully glycosylated northern and southern fragments
De Brabander, Jef K.,Hollibaugh, Ryan,Yu, Xueliang
, (2020/10/27)
Efficient approaches that enable the synthesis of analogs of natural product antibiotics are needed to keep up with the emergence of multiply-resistant strains of pathogenic organisms. One promising candidate in this area is fidaxomicin, which boasts impressive in vitro anti-tubercular activity but has poor systemic bioavailability. We designed a flexible synthetic route to this target to enable the exploration of new chemical space and the future development of analogs with superior pharmacokinetics. We developed a robust approach to each of the key macrocyclic and sugar fragments, their union via stereoselective glycosylation, and a convergent late-stage macrolide formation with fully glycosylated fragments. Although we were able to demonstrate that the final Suzuki cross-coupling and ring-closing metathesis steps enabled macrocycle formation in the presence of the northern resorcylic rhamnoside and southern novioside sugars, these final steps were hampered by poor yields and the formation of the unwanted Z-macrocycle as the major stereoisomer.
A photochemical entry to depsides: Synthesis of gustastatin
Garcia-Fortanet, Jorge,Debergh, John R.,De Brabander, Jef K.
, p. 685 - 688 (2007/10/03)
(Chemical Equation Presented) Herein, we propose a modular and general strategy to construct orcinol-type depsides based on the photolysis of functionalized benzodioxinones (I). Notably, resorcinylic esters are obtained without competing isocoumarin (II) formation, exemplified by the first total synthesis of gustastatin in 10 steps from commercially available trihydroxybenzoic acid.
