环氧乙烷
化学
立体化学
环氧化物
戒指(化学)
有机化学
催化作用
作者
Changkang Li,Xiaonan Yin,Shuai Wang,Songyang Sui,Jimei Liu,Xincheng Sun,Jinming Di,Ridao Chen,Dawei Chen,Yaotian Han,Kebo Xie,Jungui Dai
标识
DOI:10.1002/anie.202407070
摘要
Oxetane synthase (TmCYP1), a novel cytochrome P450 enzyme from Taxus × media cell cultures, has been functionally characterized to efficiently catalyse the formation of the oxetane ring in tetracyclic taxoids. Transient expression of TmCYP1 in Nicotiana benthamiana using 2α,5α,7β,9α,10β,13α‐hexaacetoxytaxa‐4(20),11(12)‐diene (1) as a substrate led to the production of a major oxetane derivative, 1β‐dehydroxybaccatin IV (1a), and a minor 4β,20‐epoxide derivative, baccatin I (1b). However, feeding the substrate decinnamoyltaxinine J (2), a 5‐deacetylated derivative of 1, yielded only 5α‐deacetylbaccatin I (2b), a 4β,20‐epoxide. A possible reaction mechanism was proposed on the basis of substrate‐feeding, 2H and 18O isotope labelling experiments, and density functional theory calculations. This reaction could be an intramolecular oxidation‐acetoxyl rearrangement and the construction of the oxetane ring may occur through a concerted process; however, the 4β,20‐epoxide might be a shunt product. In this process, the C5‐O‐acetyl group in substrate is crucial for the oxetane ring formation but not for the 4(20)‐epoxy ring formation by TmCYP1. These findings provide a better understanding of the enzymatic formation of the oxetane ring in paclitaxel biosynthesis.
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