高校化学工程学报2025，Vol.39Issue(6)：1034-1043,10.DOI:10.3969/j.issn.1003-9015.2025.00.045
可溶性标签辅助的连续流高效绿色合成Heterophyllin B
Highly efficient green synthesis of Heterophyllin B assisted by a soluble tag under continuous flow
摘要
Abstract
In response to the problems existing in the traditional synthesis of cyclic peptides,such as the use of tox-ic solvents(e.g.,DMF,DCM),controlled use of deprotection reagents(e.g.,piperidine),low cyclization effi-ciency,and the dependence on specific amino acids(e.g.,Cys,Lys),this work proposed a green and efficient strategy for cyclic peptide synthesis.This strategy is based on a novel soluble silicon-based hydrophobic tag,(bis(4-((triisopropylsilyl)oxy)phenyl)methyl)hydrazine(BTPH),combined with continuous flow microre-actor technology,to construct an integrated system consisting of three modules:coupling,deprotection(using tetra-hydropyrole instead of piperidine),and washing and extraction.Moreover,low-toxicity ethyl acetate is used to re-place traditional harmful solvents like DMF.The results show that this strategy can efficiently synthesize the linear Heterophyllin B peptide hydrazine,with a crude product purity of over 90％.The cyclization is completed through an in-situ generated acyl azide intermediate under mild conditions,with a cyclization conversion rate over 30％higher than traditional methods,improved atom economy,and a reduction in overall synthesis cost by approximately 60％.This study provides a feasible path for the green continuous flow synthesis of natural cyclic peptides and has significant reference value for the modular preparation of complex peptides.关键词
可溶性标签/Heterophyllin B/连续流动/微通道反应器Key words
soluble tag/Heterophyllin B/continuous-flow/microchannel reactors分类
化学化工引用本文复制引用
夏超,颜阳丽,黄玉龙,苏贤斌..可溶性标签辅助的连续流高效绿色合成Heterophyllin B[J].高校化学工程学报,2025,39(6):1034-1043,10.基金项目
江苏高校优势学科建设工程资助项目(PAPD). （PAPD）
