10.1002/anie.201900243
Angewandte Chemie International Edition
COMMUNICATION
product 11 in 35% yield (HPLC). In contrast, the Ag(I)-promoted
macrocyclization of the peptide thioamide 13 was complete in less
than one hour, generating the product 11 in 83% yield (HPLC)
(Figure 3).
In conclusion, a single-atom (O®S) substitution of a linear
peptide – through incorporation of a thioamide at the N-terminal
backbone amide position – facilitates and rapid and traceless
Ag(I)-promoted macrocyclization process. Cyclic peptides are
furnished in excellent yield, free of epimerization and
cyclodimerization.
O
O
H
N
H
O
O
N
O
N
H
H2N
N
H
HN
X
HN
NH
NBoc
NBoc
O
O
O
N
N
O
O
N
H
N
TrtHN
Acknowledgements
BocN
O
O
O
O
H
N
X = S: Ag2CO3
NH
HO2C
N
This work was supported by the Australian Research Council
(DP180101804 and DP150100692). We acknowledge the
support of the Bio21 Molecular Science and Biotechnology
Institute MSP and Peptide Technologies facilities. V.T.
acknowledges the award of a Norma Hilda Schuster Scholarship.
NH
N
H
N
BocN
H
O
X = O: HATU,
DIPEA
HN
1 mM, CH3CN
TrtHN
O
HN
HN
HN
NHPbf
NHPbf
11
12 X = O
13 X = S
Keywords: macrocyclization • cyclic peptide • thioamide
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