Li Heng, Goldfuss Bernd, Dickschat Jeroen S
Kekulé Institute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Straße 1, 53121, Bonn, Germany.
Department for Chemistry, University of Cologne, Greinstrasse 4, 50939, Cologne, Germany.
Angew Chem Int Ed Engl. 2025 Mar 24;64(13):e202422788. doi: 10.1002/anie.202422788. Epub 2025 Jan 10.
Taxa-4,11-diene is made by the taxa-4,11-diene synthase (TxS) from Taxus brevifolia. The unique reactivity of the taxane system is characterised by long distance hydrogen migrations in the biosynthesis. This study demonstrates that selective long range hydrogen migrations also play a role in the high energy process of the EI-MS fragmentation of taxa-4,11-diene. A TxS enzyme variant was generated that produces cyclophomactene, a compound that is formed through a concerted process involving a long range proton shift and a ring closure that can also be described as the addition of a methylcarbinyl cation to an olefin. Based on a previous computational study the cyclisation mechanism towards taxa-4,11-diene was suggested to involve two long distance proton migrations instead of one direct transfer. A substrate analog with a shifted double bond was converted with TxS to obtain experimental evidence for this proposal.
紫杉-4,11-二烯由短叶红豆杉中的紫杉-4,11-二烯合酶（TxS）合成。紫杉烷体系独特的反应活性在生物合成过程中表现为长距离氢迁移。本研究表明，选择性长程氢迁移在紫杉-4,11-二烯电子轰击质谱（EI-MS）碎裂的高能过程中也发挥作用。生成了一种TxS酶变体，它能产生环佛波烯，该化合物通过一个协同过程形成，此过程涉及长程质子转移和环化反应，这也可描述为甲基碳正离子加成到烯烃上。基于之前的计算研究，有人提出紫杉-4,11-二烯的环化机制涉及两个长距离质子迁移而非一个直接转移。通过用TxS转化一个双键位置发生改变的底物类似物来为这一推测获取实验证据。
