Total Synthesis of Tambromycin by Combining Chemocatalytic and Biocatalytic C−H Functionalization

A combination of genomic and metabolomic approaches recently resulted in the identification of a nonribosomal tetrapeptide tambromycin, which possesses promising antiproliferative activity and several unusual structural features, including a densely substituted indole, a methyloxazoline ring, and an...

Full description

Saved in:
Bibliographic Details
Published in:Angewandte Chemie 2018-04, Vol.130 (18), p.5131-5135
Main Authors: Zhang, Xiao, King‐Smith, Emma, Renata, Hans
Format: Article
Language:English
Subjects:
Amino acids
Biokatalyse
C-H-Funktionalisierung
Chemical synthesis
Chemistry
Dioxygenase
Indoles
Metabolomics
Naturstoffe
Nichtribosomale Peptide
Pyrrolidine
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:A combination of genomic and metabolomic approaches recently resulted in the identification of a nonribosomal tetrapeptide tambromycin, which possesses promising antiproliferative activity and several unusual structural features, including a densely substituted indole, a methyloxazoline ring, and an unusual pyrrolidine‐containing amino acid called tambroline. In this work, we identify a concise synthetic route to access tambromycin, which relies on the strategic use of biocatalytic and chemocatalytic C−H functionalization methods to prepare two key precursors to the natural product in an efficient and scalable manner. The success of our study highlights the benefits of applying the principles of biocatalytic retrosynthesis as well as C−H functionalization logic to the synthesis of complex molecular scaffolds. Von zwei Seiten: Tambromycin, ein zytotoxisches nichtribosomales Peptid, das eine Pyrrolidinyl‐Aminosäure enthält, wurde mit einer Kombination aus chemo‐ und biokatalysierter C‐H‐Funktionalisierung synthetisiert. Wichtige Schritte sind die enzymatische C‐H‐Hydroxylierung einer ungeschützten Aminosäure, eine iridiumkatalysierte regioselektive Indolfunktionalisierung und eine chemoselektive Peptidkupplung in Gegenwart zahlreicher reaktiver Gruppen.
ISSN:0044-8249
1521-3757
DOI:10.1002/ange.201801165