摘要/Abstract
以水、重氮乙酸酯、芳香醛和芳香胺为原料，在单一催化剂Cu（OTf）2的作用下成功实现了一例基于羟基叶立德捕捉的四组分反应，一步构建了α-羟基-β-氨基酸酯类化合物骨架，并通过进一步的化学转化高效地合成了紫杉醇噁唑烷型侧链.此外，将所得侧链与紫杉醇母核、卡巴他赛母核对接，成功合成了14个紫杉醇衍生物，并在随后的抗肿瘤细胞活性测试中，发现了多个活性优异的新型化合物.将多组分反应方法学与应用相结合，开发了一种高效合成紫杉醇侧链衍生物的方法，并成功地将其应用到紫杉醇衍生物的半合成中，为该类化合物的构效关系研究提供了一种新途径，具有潜在的应用价值.
关键词: 紫杉醇侧链, 紫杉醇衍生物, 多组分反应, 羟基叶立德
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.
Key words: taxol side chain, paclitaxel analogues, multi-component reaction, hydroxy ylide
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