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
收稿日期: 2018-07-24
修回日期: 2018-12-17
网络出版日期: 2018-12-21
基金资助
国家自然科学基金（Nos.21572067，21332003）资助项目.
Synthesis of Paclitaxel Side Chain via Multi-Component Reaction and Its Application to the Synthesis of Paclitaxel Analogues
Received date: 2018-07-24
Revised date: 2018-12-17
Online published: 2018-12-21
Supported by
Project supported by the National Natural Science Foundation of China (Nos. 21572067, 21332003).
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.
盛家骏 , 于雅楠 , 王信 , 钱宇 , 符立梧 , 赵芸 , 马明亮 , 胡文浩 . 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[J]. 有机化学, 2019 , 39(2) : 377 -389 . DOI: 10.6023/cjoc201806031
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.
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