The -mono-glucoside (95 yield; 9 mM) appropriate for biological studies. Keyword phrases: cinmethylin, Leloir glycosyltransferase, glycosylation, xenobiotic metabolism, agricultural herbicideINTRODUCTION Plant protection chemical substances represent a quickly growing sector within the agrochemical industries. Fatty Acid Synthase (FASN) web Amongst these chemical compounds, herbicides are critical active substances to control weed growth. Approval procedures for herbicides require detailed evaluation of environmental safety.1-4 The assessment from the fate and behavior inside the environment entails that not only the original substances but Fat Mass and Obesity-associated Protein (FTO) Purity & Documentation additionally their detoxification metabolites are closely monitored.3,five,6 Cinmethylin (Figure 1) is a well-known benzyl-ether derivative of the organic terpene 1,4-cineole.7-9 Cinmethylin is employed industrially as a pre-emergence herbicide for crop protection.7-10 Commercialized cinmethylin-based products are marketed for integrated grass weed management (e.g., Luximax and Luximo) to supply manage against numerous grasses (e.g., ryegrass and blackgrass) with developed resistance(s). Cinmethylin is classified into group Z in the herbicide mode of action groups, implying interference with the cellular membrane structure and function due to the inhibition of fatty acid thioesterases by cinmethylin-derived 1,4-cineole.7 Metabolic studies in animals (e.g., rat and goat) assistance the idea that phase I detoxification of cinmethylin involves single- and multiple-site hydroxylation events.11,12 Amongst the cinmethylin metabolites located in goats, the benzylic C15 methyl group of cinmethylin was a prominent web site for hydroxylation.12 Indirect proof from cinmethylin efficacy research in plants supports a function of cytochrome P450 hydroxylases in compound detoxification.9 Additional (phase II) detoxification of hydroxylated cinmethylin metabolites would most likely involve glycosylation, using a -D-glucosyl residue attached in plants3,5,6,13 along with a -D-glucuronyl residue attached2021 The Authors. Published by American Chemical Societyin animals.14,15 The current study was performed to develop a biocatalytic synthesis for the -D-glucoside of 15-hydroxy cinmethylin (Figure 1). The 15-hydroxy cinmethylin was synthesized chemically. The resulting 15-hydroxy cinmethylin -D-glucoside was of considerable interest to facilitate later biological studies of cinmethylin metabolism related with cinmethylin in planta efficacy. Despite the fact that chemical glycosylation of 15-hydroxy cinmethylin could be attainable working with basic methodology,16 an enzymatic route that enables selective glucosylation of unprotected reactants within a flexibly scaled, single-step transformation is highly desirable and has not been described. To prepare the 15-hydroxy cinmethylin–D-glucoside (Figure 1), we initial viewed as no matter if to embark on glycosylation by glycoside hydrolases/trans-glycosidases,17-21 glycoside phosphorylases,22-25 or sugar nucleotide-dependent (Leloir) glycosyltransferases (GTs).26-31 Every single enzyme kind could in principle be made use of to glycosylate 15-hydroxy cinmethylin. Even so, small-molecule glycosylation in detoxification metabolism is naturally performed by GTs.six,13 In plants, these enzymes use uridine 5-diphosphate (UDP)glucose as the sugar donor.26,27 Substrate specifications of theReceived: Revised: Accepted: Published: March four, 2021 April 27, 2021 April 28, 2021 May 11,https://doi.org/10.1021/acs.jafc.1c01321 J. Agric. Meals Chem. 2021, 69, 5491-Journal of Agricultural and Meals Chemistrypubs.acs.org/JAFCArticleFigure 1. Cinm.
