The stereo- and regioselective oxidative functionalization of olefins is amongst the most challenging reactions in organic syntheses. In particular, the catalytic asymmetric dihydroxylation of alkenes has attracted considerable attention due to the facile further transformation of the chiral diol products into valuable derivatives, making them important building blocks for the pharmaceutical and chemical industry. Nature’s creativity in developing solutions for C–H-bond functionalization reactions like hydroxylations at activated or non-activated C–H-bonds is remarkably shown by an impressive list of metal-dependent enzymes. These enzymes, like the Rieske non-heme iron oxygenases (ROs) are able to activate molecular oxygen in order to generate reactive oxygen species capable of hydroxylating alkyl-substrates and they also promote further oxidative transformations. For many of these reactions no ‘classical’ chemical counterpart is known. ROs represent promising biocatalysts for these reactions since they are the only enzymes known to catalyze the stereoselective formation of vicinal cis-diols in one step. They are soluble multicomponent systems that harness the reductive power of NAD(P)H for oxygen activation. Due to their versatility, ROs are considered as the non-heme analogues of cytochrome P450 monooxygenases and, in addition to their relaxed substrate specificity, these enzymes can also catalyze various oxidation reactions, resulting in an enormous potential of these enzymes for manifold synthetically useful transformations. This chapter describes the current understanding of the structural determinants and the catalytic behavior of dioxygenase-catalyzed reactions, and highlights how in several cases this knowledge has been harnessed to design tailored catalysts for the synthesis of various natural products, polyfunctionalized metabolites and pharmaceutical intermediates. Moreover, the chapter also gives insights into recently characterized ROs catalyzing unusual reactions as well as applications in chemo-enzymatic cascade reactions for natural product synthesis.
|Title of host publication||Biocatalysis|
|Subtitle of host publication||Enzymatic Basics and Applications|
|Editors||Qayyum Husain, Mohammad Fahad Ullah|
|Publisher||Springer International Publishing AG|
|Number of pages||26|
|Publication status||Published - 4-Sep-2019|