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Total Synthesis of Tiacumicin B: Implementing Hydrogen Bond Directed Acceptor Delivery for Highly Selective β‐Glycosylations
Author(s) -
Norsikian Stéphanie,
Tresse Cedric,
FrançoisEude Marc,
JeanneJulien Louis,
Masson Guillaume,
Servajean Vincent,
GentaJouve Grégory,
Beau JeanMarie,
Roulland Emmanuel
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202000231
Subject(s) - aglycone , chemistry , total synthesis , hydrogen bond , anomer , stereochemistry , combinatorial chemistry , ring (chemistry) , organic chemistry , molecule , glycoside
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.