Yongqi He, Xin-Yu Leng, Runying Wang, Lulu Sun, Dan Zhang, Yushe Yang
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引用次数: 0
Abstract
In previous studies, we discovered YZD-7082B, a selective estrogen receptor degrader (SERD) with excellent comprehensive properties. Here, we reported the development of an efficient multigram-scale synthetic process for YZD-7082 in 13 steps. The route featured a chiral resolution of a thiochroman intermediate with a unique cis-1,2-diaryl motif using a chiral amine and a mild reduction of amide using ZnEt2/LiCl/(EtO)3SiH system. This approach also overcomes the issues of high loadings of palladium catalysts and long reaction time. The developed process provided YZD-7082B with an HPLC purity of > 99.8% and ee of > 99%.
期刊介绍：
Molecular Diversity is a new publication forum for the rapid publication of refereed papers dedicated to describing the development, application and theory of molecular diversity and combinatorial chemistry in basic and applied research and drug discovery. The journal publishes both short and full papers, perspectives, news and reviews dealing with all aspects of the generation of molecular diversity, application of diversity for screening against alternative targets of all types (biological, biophysical, technological), analysis of results obtained and their application in various scientific disciplines/approaches including:
combinatorial chemistry and parallel synthesis;
small molecule libraries;
microwave synthesis;
flow synthesis;
fluorous synthesis;
diversity oriented synthesis (DOS);
nanoreactors;
click chemistry;
multiplex technologies;
fragment- and ligand-based design;
structure/function/SAR;
computational chemistry and molecular design;
chemoinformatics;
screening techniques and screening interfaces;
analytical and purification methods;
robotics, automation and miniaturization;
targeted libraries;
display libraries;
peptides and peptoids;
proteins;
oligonucleotides;
carbohydrates;
natural diversity;
new methods of library formulation and deconvolution;
directed evolution, origin of life and recombination;
search techniques, landscapes, random chemistry and more;
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