26. Stereoconvergent reduction of alkenes using a repurposed iron-based dioxygenase
The stereoconvergent reduction of alkenes for efficient synthesis of chiral compounds is a challenge in synthetic chemistry, even for exquisite enzymes in nature. Natural ene-reductases for example generally catalyse the reduction of alkenes in an enantiodivergent or resolution fashion. Here we report the repurposing of non-haem iron-based dioxygenases to catalyse the stereoconvergent reduction of alkenes through an iron hydride intermediate, by introducing silanes to the biocatalytic system. Directed evolution of gentisate 1,2-dioxygenase led to iron-based ene-reductases with high efficiency (up to 99% yield), excellent enantioselectivity (23 examples with >99% e.e.) and compatibility with a structurally diverse range of substrates. Experimental studies suggest the formation of iron hydride species in the enzyme and support the divalency of iron during the catalytic process. Computational studies show that the reaction is energetically feasible through an iron hydride mechanism and reveal the molecular mechanism of stereoconvergence.
通过烯烃的立体汇聚还原高效合成手性化合物是合成化学中的一大挑战，即使对于自然界中精妙的酶而言也是如此。例如，天然烯还原酶通常以对映发散或拆分的方式催化烯烃的还原。本文，我们报道了通过将硅烷引入生物催化系统，将非血红素铁基双加氧酶重新利用，使其能够通过铁氢化物中间体催化烯烃的立体收敛还原。龙胆酸 1,2-双加氧酶的定向进化产生了高效率（产率高达 99%）、优异的对映选择性（23 个实例的对映选择性 >99%）并且与结构多样的底物兼容的铁基烯还原酶。实验研究表明酶中形成了铁氢化物物质，并支持催化过程中铁的二价性。计算研究表明，该反应通过铁氢化物机理在能量上可行，并揭示了立体聚合的分子机理。