4.6 Article

Total Synthesis of Tiacumicin B: Study of the Challenging β-Selective Glycosylations**

Journal

CHEMISTRY-A EUROPEAN JOURNAL
Volume 27, Issue 16, Pages 5230-5239

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.202005102

Keywords

antibiotics; cis-glycosylation; glycochemistry; natural products; total synthesis

Funding

  1. French Agence Nationale pour la Recherche [ANR-14-CE16-0019-02]
  2. CNRS
  3. Universite de Paris
  4. Agence Nationale de la Recherche (ANR) [ANR-14-CE16-0019] Funding Source: Agence Nationale de la Recherche (ANR)

Ask authors/readers for more resources

The total synthesis of tiacumicin B was achieved by utilizing glycosylation steps and Suzuki-Miyaura cross-coupling. Unique glycosylation steps and macrolactonization techniques were used to successfully synthesize tiacumicin B.
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 beta-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 beta-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.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available