Foja Richard, Walter Alexandra, Jandl Christian, Thyrhaug Erling, Hauer Jürgen, Storch Golo
Department of Chemistry, Technical University of Munich, Lichtenbergstrasse 4, 85747 Garching, Germany.
J Am Chem Soc. 2022 Mar 23;144(11):4721-4726. doi: 10.1021/jacs.1c13285. Epub 2022 Mar 8.
Flavoenzymes mediate a multitude of chemical reactions and are catalytically active both in different oxidation states and in covalent adducts with reagents. The transfer of such reactivity to the organic laboratory using simplified molecular flavins is highly desirable, and such applications in (photo)oxidation reactions are already established. However, molecular flavins have not been used for the reduction of organic substrates yet, although this activity is known and well-studied for DNA photolyase enzymes. We report a catalytic method using reduced molecular flavins as photoreductants and γ-terpinene as a sacrificial reductant. Additionally, we present our design for air-stable, reduced flavin catalysts, which is based on a conformational bias strategy and circumvents the otherwise rapid reduction of O from air. Using our catalytic strategy, we were able to replace superstoichiometric amounts of the rare-earth reductant SmI in a 5--trig cyclization of substituted barbituric acid derivatives. Such flavin-catalyzed reductions are anticipated to be beneficial for other transformations as well and their straightforward synthesis indicates future use in stereo- as well as site-selective transformations.
黄素酶介导多种化学反应，在不同氧化态以及与试剂形成的共价加合物中均具有催化活性。使用简化分子黄素将这种反应活性转移到有机实验室中是非常可取的，并且这种在（光）氧化反应中的应用已经得到确立。然而，分子黄素尚未用于有机底物的还原反应，尽管这种活性在DNA光解酶中是已知且经过充分研究的。我们报道了一种使用还原态分子黄素作为光还原剂和γ-萜品烯作为牺牲还原剂的催化方法。此外，我们展示了基于构象偏向策略的空气稳定型还原黄素催化剂的设计，该设计避免了空气中的氧对其进行快速还原。利用我们的催化策略，我们能够在取代巴比妥酸衍生物的5-环化反应中替代化学计量过量的稀土还原剂SmI₂。预计这种黄素催化的还原反应对其他转化也将有益，并且其简单的合成方法表明其在立体选择性和位点选择性转化中的未来应用。
