888958-31-4Relevant articles and documents
A convergent approach toward fidaxomicin: Syntheses of the fully glycosylated northern and southern fragments
De Brabander, Jef K.,Hollibaugh, Ryan,Yu, Xueliang
, (2020)
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.
Syntheses of epi-aigialomycin D and deoxy-aigialomycin C via a diastereoselective ring closing metathesis macrocyclization protocol
Bajwa, Naval,Jennings, Michael P.
, p. 390 - 393 (2008/09/17)
Syntheses of epi-aigialomycin D and deoxy-aigialomycin C are described via a remote stereocontrolled RCM macrocyclization.
Efficient and selective reduction protocols of the 2,2-dimethyl-1,3- benzodioxan-4-one functional group to readily provide both substituted salicylaldehydes and 2-hydroxybenzyl alcohols
Bajwa, Naval,Jennings, Michael P.
, p. 3646 - 3649 (2007/10/03)
Two complementary procedures have been developed that selectively allow for the synthesis of either substituted salicylaldehydes or the corresponding 2-hydroxylbenzyl alcohols upon treatment of the 2,2-dimethyl-1,3-benzodioxan-4- one functional group with DIBAL-H or LAH, respectively.
