Several chemoenzymatic routes have been explored for the preparation of cinacalcet, a calcimimetic agent. Transaminases (TAs) and ketoreductases (KREDs) turned out to be useful biocatalysts for the preparation of key optically active precursors. Thus, the asymmetric amination of 1‐acetonaphthone yielded an enantiopure (R)‐amine, which can be alkylated in one step to yield cinacalcet. Alternatively, the bioreduction of the same ketone resulted in an enantiopure (S)‐alcohol, which was easily converted into the previous (R)‐amine. In addition, the reduction was efficiently performed with the KRED and its cofactor co‐immobilized on the same porous surface. This self‐sufficient heterogeneous biocatalyst presented an accumulated total turnover number (TTN) for the cofactor of 675 after 5 consecutive operational cycles. Finally, in a preparative scale synthesis the TA‐based approach was performed in aqueous medium and led to enantiopure cinacalcet in two steps and 50% overall yield.

中文翻译：

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化学酶法利用转氨酶和酮还原酶合成拟钙剂西那卡塞的方法

已经探索了几种化学酶促途径来制备拟钙剂西那卡塞。事实证明，转氨酶（TAs）和酮还原酶（KRED）是用于制备关键旋光前体的有用生物催化剂。因此，1-乙酰萘酮的不对称胺化反应产生了对映纯（R）-胺，可将其一步烷基化以生成西那卡塞。另外，对相同的酮进行生物还原可产生对映纯（S）-醇，很容易将其转化为对映体（R））-胺。此外，将KRED及其辅因子共固定在同一多孔表面上可有效地进行还原。在连续5个操作周期后，这种自给自足的异质生物催化剂呈现出675个辅助因子的累积总周转数（TTN）。最后，在制备规模的合成中，基于TA的方法在水性介质中进行，并分两步完成对映纯西那卡塞，总收率为50％。