NDTP Mediated Direct Rapid Amide and Peptide Synthesis without Epimerization
Yiping Li, Jingyue Li, Guangjun Bao, Changjun Yu, Yuyang Liu, Zeyuan He, Peng Wang, Wen Ma, Junqiu Xie, Wangsheng Sun* and Rui Wang*
*School of Basic Medical Sciences & Research Unit of Peptide
Science, CAMS, 2019RU066, Lanzhou University, 199 West Donggang Rd., Lanzhou 730000, Gansu, P. R. China,
Email: sunws
lzu.edu.cn, wangruilzu.edu.cn
Y. Li, J. Li, G. Bao, C. Yu, Y. Liu, Z. He, P. Wang, W. Ma, J. Xie, W. Sun, R. Wang, Org. Lett., 2022, 24, 1169-1174.
DOI: 10.1021/acs.orglett.1c04258
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Abstract
NDTP is an unprecedented mild, nonirritating, conveniently available, and recyclable coupling reagent, which activates carboxylic acids via acyl thiocyanide and enables a rapid amide and peptide synthesis at very mild conditions. In addition, the methodology is compatible with Fmoc-SPPS.
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proposed reaction pathway and recycling of reagent
General Procedures
With DIPEA:
To a solution of carboxylic acid (0.15 mmol), amine or amine hydrochloride (0.10 mmol) and DIPEA (0.3 mmol, 3 eq or 0.4 mmol, 4 eq.) in MeCN (0.5 mL) was added a solution of NDTP (0.15 mmol) in MeCN (0.5 mL) and stirred for 1 minute. Then the solvent was evaporated under reduced pressure, and the residue was purified by flash column chromatography (EtOAc/hexane = 1:1 - 1:3 or MeOH/CH2Cl2 = 1:10).
With DABCO:
To a solution of carboxylic acid (0.15 mmol), amine (0.10 mmol) and DABCO (0.6 mmol, 6 eq.) in MeCN (0.5 mL) was added a solution of NDTP (0.15 mmol) in MeCN (0.5 mL) and stirred for 1 minute. Then the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography (EtOAc/hexane = 1:1- 1:3 or MeOH/CH2Cl2 = 1:10).
Key Words
ID: J54-Y2022
