Sprecher
Beschreibung
Modern flavoenzymes are among nature’s most versatile catalysts and mediate reactions ranging from oxidations, oxygenations, ring contractions, to reductions [1]. This diversity stems from the occurrence of different catalytically active states of the cofactor’s isoalloxazine heterocycle, which is the reactive center of both flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). However, the astonishingly broad reactivity spectrum of flavoenzymes stands in contrast to the
currently limited synthetic use of molecular flavins [2]. Their plausible prebiotic origin also raises the question whether flavins played an important role in mediating crucial transformations at the molecular origins of life [3]. In order to bridge this gap, we focus on the synthesis and application of molecular flavin catalysts in organic transformations.
Our first example uses C6-ester-modified flavins [FlCat]* for the modification of dehydroamino acids. We showed that covalent flavin adducts are involved and that β-alkoxamines are obtained with the persistent radical TEMPO under catalytic conditions [4]. Inspired by the activity of flavin hydroperoxides [FlCat-C4a-OOH] in halogenases, we prepared molecular flavins for O2-reduction and subsequent bromination with inorganic halide salt [5]. Modified catalysts are operative under mild conditions, while the isolated cofactor (‒)-riboflavin is unproductive. We have also found a strategy to use visible-light excitation of flavins for one-electron reduction of barbiturate substrates, replacing the typically used super-stoichiometric metal reductants with the essential oil γ-terpinene [6].
References:
1. (a) M. Toplak, R. Teufel, Biochemistry 2022, 61, 47–56; (b) C. T. Walsh, T. A. Wencewicz, Nat. Prod. Rep. 2013, 30, 175‒200.
2. A. Rehpenn, A. Walter, G. Storch, Synthesis 2021, 53, 2583‒2593.
3. A. Kirschning, Angew. Chem. Int. Ed. 2021, 60, 6242‒6269.
4. A. Rehpenn, A. Walter, G. Storch, Chem. Sci. 2022, 13, 14151‒14156.
5. A. Walter, G. Storch, Angew. Chem. Int. Ed. 2020, 59, 22505‒22509.
6. R. Foja, A. Walter, C. Jandl, E. Thyrhaug, J. Hauer, G. Storch, J. Am. Chem. Soc. 2022, 144, 4721‒4726.
