多组分反应合成紫杉醇侧链及其在合成紫杉醇衍生物中的应用

Under the catalysis of Cu(OTf) ₂ , a hydroxy ylide trapping based multi-component reaction using water, diazoacetates, aromatic aldehydes and aromatic amines was successfully carried out to construct α-hydroxy-β-amino acid ester skeleton in one step. The taxol oxazolidine-type side chains were efficiently synthesized after further chemical transformations. Moreover, 14 taxane derivatives were synthesized through esterification of obtained side chains and 7-O-(triethylsilyl) baccatin Ⅲ or 7,10-dimethoxy-10-beacetyl baccatin Ⅲ, and several novel compounds with excellent activity were discovered in the test of anti-tumor activity. In this paper, combining the methodology and application of multi-component reaction, a highly efficient method for synthesizing paclitaxel side chain derivatives was developed, which was applied into the semi-synthesis of paclitaxel analogues. This research provided a new approach to the study of structure-activity relationship and had potential application value.