Chen Ying-Ying, Chang Li-Te, Chen Hung-Wei, Yang Chia-Ying, Hsin Ling-Wei
School of Pharmacy, College of Medicine, ‡Molecular Probes Development Core, Molecular Imaging Center, and §Center for Innovative Therapeutics Discovery, National Taiwan University , 17, Xuzhou Road, Room 936, Taipei 10055, Taiwan.
ACS Comb Sci. 2017 Mar 13;19(3):131-136. doi: 10.1021/acscombsci.6b00160. Epub 2017 Jan 18.
A fast and facile synthesis of a series of 4-nitrophenyl 2-azidoethylcarbamate derivatives as activated urea building blocks was developed. The N-Fmoc-protected 2-aminoethyl mesylates derived from various commercially available N-Fmoc-protected α-amino acids, including those having functionalized side chains with acid-labile protective groups, were directly transformed into 4-nitrophenyl 2-azidoethylcarbamate derivatives in 1 h via a one-pot two-step reaction. These urea building blocks were utilized for the preparation of a series of urea moiety-containing mitoxantrone-amino acid conjugates in 75-92% yields and parallel solution-phase synthesis of a urea compound library consisted of 30 members in 38-70% total yields.
开发了一种快速简便的方法来合成一系列4-硝基苯基2-叠氮基乙基氨基甲酸酯衍生物作为活化脲结构单元。从各种市售的N-Fmoc保护的α-氨基酸衍生而来的N-Fmoc保护的2-氨基乙基甲磺酸酯，包括那些具有带酸不稳定保护基的官能化侧链的氨基酸，通过一锅两步反应在1小时内直接转化为4-硝基苯基2-叠氮基乙基氨基甲酸酯衍生物。这些脲结构单元用于制备一系列含脲部分的米托蒽醌-氨基酸缀合物，产率为75-92%，并以38-70%的总产率平行溶液相合成了一个由30个成员组成的脲化合物库。
