27808-83-9Relevant academic research and scientific papers
Total Synthesis of Tiacumicin B: Implementing Hydrogen Bond Directed Acceptor Delivery for Highly Selective β-Glycosylations
Beau, Jean-Marie,Fran?ois-Eude, Marc,Genta-Jouve, Grégory,Jeanne-Julien, Louis,Masson, Guillaume,Norsikian, Stéphanie,Roulland, Emmanuel,Servajean, Vincent,Tresse, Cedric
, p. 6612 - 6616 (2020)
A total synthesis of tiacumicin B, a natural macrolide whose remarkable antibiotic properties are used to treat severe intestinal infections, is reported. The strategy is in part based on the prior synthesis of the tiacumicin B aglycone, and on the decisive use of sulfoxides as anomeric leaving groups in hydrogen-bond-mediated aglycone delivery (HAD). This new HAD variant permitted highly β-selective rhamnosylation and noviosylation. To increase convergence, the rhamnosylated C1–C3 fragment thus obtained was anchored to the C4–C19 aglycone fragment by adapting the Suzuki–Miyaura cross-coupling used for the aglycone synthesis. Ring-size-selective macrolactonization provided a compound engaged directly in the noviolysation step with virtually total β selectivity. The final efficient removal of all the protecting groups provided synthetic tiacumicin B.
Total Synthesis of Tiacumicin B: Study of the Challenging β-Selective Glycosylations**
Tresse, Cédric,Fran?ois-Heude, Marc,Servajean, Vincent,Ravinder, Rubal,Lesieur, Clémence,Geiben, Lucie,Jeanne-Julien, Louis,Steinmetz, Vincent,Retailleau, Pascal,Roulland, Emmanuel,Beau, Jean-Marie,Norsikian, Stéphanie
supporting information, p. 5230 - 5239 (2021/02/26)
We give a full account of the total synthesis of tiacumicin B (Tcn-B), a natural glycosylated macrolide with remarkable antibiotic properties. Our strategy is based on our experience with the synthesis of the tiacumicin B aglycone and on unique 1,2-cis-glycosylation steps. We used sulfoxide anomeric leaving-groups in combination with a remote 3-O-picoloyl group on the donors that allowed highly β-selective rhamnosylation and noviosylation that rely on H-bond-mediated aglycone delivery. The rhamnosylated C1–C3 fragment was anchored to the C4–C19 aglycone fragment by a Suzuki–Miyaura cross-coupling. Ring-size-selective Shiina macrolactonization provided a semiglycosylated aglycone that was engaged directly in the noviolysation step with a virtually total β-selectivity. Finally, a novel deprotection method was devised for the removal of a 2-naphthylmethyl ether on a phenol, and efficient removal of all the protecting groups provided synthetic tiacumicin B.
