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Journal of the American Chemical Society
DHP alkylation reagents. Importantly, the unsubstituted nitro-
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modification of a series of important peptide drugs, complex
natural products, and a small protein. We are optimistic this
method will provide a useful tool to label and fine-tune histidine
residues of molecules for both biological and medicinal chem-
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EXPERIMENTAL SECTION
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Typical procedure for chemoselective CH alkylation of His
under LED irradiation: Saralasin 6 (106.5 mg, 93.4 μmol, 1.0
equiv.), DHP-a (312.7 mg, 0.93 mmol, 10.0 equiv.), degassed
TFA (70 μL, 0.93 mmol, 10.0 equiv.) and TFE (9.35 mL, 10
mM) were added into a glass vial (20 mL). The mixture was
gently purged by argon for 2 mins and sealed with a cap. The
reaction mixture was stirred under argon atmosphere and irra-
diated with two blue LEDs (10 W, 3 cm from the vial) for 3
hours. The reaction temperature was kept around 35 ºC with a
cooling fan. The reaction mixture was concentrated with a
stream of argon and precipitated with the addition of 10 mL of
ice-cold diethyl ether. The precipitate was collected by decanta-
tion after centrifugation and dried under reduced pressure. The
crude peptide mixture was re-subjected to the same alkylation
operation for two more rounds. The final crude product after
precipitation treatment was analyzed by LC-MS and purified by
preparative reverse phase HPLC to afford a white peptide pow-
der 6-a as a TFA salt after lyophilization (65.0 mg, 53.2 μmol,
57% yield).
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website.
Detailed experimental procedures and spectral data
AUTHOR INFORMATION
Corresponding Author
ORCID
Gong Chen: 0000-0002-5067-9889
Ping Wang: 0000-0002-8640-1483
Notes
The authors declare no competing financial interest.
Author Contributions
§X. C and F. Y. contributed equally.
ACKNOWLEDGMENT
Financial support for this work from National Natural Science
Foundation of China (21672146, 91753102 and 21907064) and
Natural Science Foundation of Shanghai (17JC1405300). The
authors thank Prof. Lifeng Pan (Shanghai Institute of Organic
Chemistry), Prof. Yimin Li (Hefei University of Technology)
and Prof. Wei. Huang (Shanghai Institute of Materia Medica)
for technical support.
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