Continuous-Flow Synthesis of (R)-Tamsulosin Utilizing Sequential Heterogeneous Catalysis
Continuous-Flow Synthesis of (R)-Tamsulosin Utilizing Sequential Heterogeneous Catalysis
复制标题
序贯多相催化连续流合成(R)-坦索罗辛
DOI：
10.1002/anie.202115643
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发表时间：
2022-02-04
影响因子：
16.6
通讯作者：
Kobayashi, Shu
中科院分区：
文献类型：
--
作者：
Saito, Yuki;Nishizawa, Ken;Kobayashi, Shu
我们描述了连续流合成（R）-坦索罗辛，一个重磅炸弹的治疗药物，用于排尿困难与泌尿系统结石和良性前列腺增生，通过利用顺序多相催化。两个非均相催化剂已开发的合成，和关键步骤涉及还原胺化腈使用二甲基聚硅烷改性的Pd活性炭/磷酸钙。总的来说，在流动物流中通过四次催化转化以60%产率和64%ee（重结晶后99%ee）获得（R）-坦索罗辛，而不需要分离或纯化任何中间体或副产物。
We describe the continuous-flow synthesis of (R)-tamsulosin, a blockbuster therapeutic drug employed for dysuria associated with urinary stones and benign prostatic hyperplasia, by utilizing sequential heterogeneous catalysis. Two heterogeneous catalysts have been developed for the synthesis, and the key step involves reductive amination of nitriles using dimethylpolysilane-modified Pd on activated carbon/calcium phosphate. Overall, (R)-tamsulosin was obtained in 60 % yield and 64 % ee (99 % ee after recrystallization) in a flow stream through four catalytic transformations without the need for the isolation or purification of any intermediates or byproduct.