Total Synthesis of Tiacumicinâ
B: Implementing Hydrogen Bond Directed Acceptor Delivery for Highly Selective ß-Glycosylations.
Angew Chem Int Ed Engl
; 59(16): 6612-6616, 2020 04 16.
Article
en En
| MEDLINE
| ID: mdl-32003915
ABSTRACT
A total synthesis of tiacumicinâ
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 tiacumicinâ
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 ß-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 ßâ
selectivity. The final efficient removal of all the protecting groups provided synthetic tiacumicinâ
B.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fidaxomicina
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Año:
2020
Tipo del documento:
Article
País de afiliación:
Francia