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Total Synthesis of Tambromycin by Combining Chemocatalytic and Biocatalytic C−H Functionalization
Author(s) -
Zhang Xiao,
KingSmith Emma,
Renata Hans
Publication year - 2018
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.201801165
Subject(s) - surface modification , nonribosomal peptide , tetrapeptide , chemistry , pyrrolidine , retrosynthetic analysis , combinatorial chemistry , natural product , isatin , stereochemistry , total synthesis , organic chemistry , enzyme , biosynthesis , biochemistry , peptide
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.