Flavin-enabled reductive and oxidative epoxide ring opening reactions

Abstract

Epoxide ring opening reactions are common and important in both biological processes and synthetic applications and can be catalyzed in a non-redox manner by epoxide hydrolases or reductively by oxidoreductases. Here we report that fluostatins (FSTs), a family of atypical angucyclines with a benzofluorene core, can undergo nonenzyme-catalyzed epoxide ring opening reactions in the presence of flavin adenine dinucleotide (FAD) and nicotinamide adenine dinucleotide (NADH). The 2,3-epoxide ring in FST C is shown to open reductively via a putative enol intermediate, or oxidatively via a peroxylated intermediate with molecular oxygen as the oxidant. These reactions lead to multiple products with different redox states that possess a single hydroxyl group at C-2, a 2,3-vicinal diol, a contracted five-membered A-ring, or an expanded seven-membered A-ring. Similar reactions also take place in both natural products and other organic compounds harboring an epoxide adjacent to a carbonyl group that is conjugated to an aromatic moiety. Our findings extend the repertoire of known flavin chemistry that may provide new and useful tools for organic synthesis.

Biochemical and structural insights of multifunctional flavin-dependent monooxygenase FlsO1-catalyzed unexpected xanthone formation

“…1 ), belong to benzofluorene-containing atypical angucyclines with enzyme inhibition and cytotoxic activities 19 , 20 . The structure diversity of FST-related angucyclines and angucyclinones was largely expanded in recent years by natural isolation 21 – 26 , heterologous expression of the biosynthetic gene cluster (BGC) 27 – 30 , and manipulation of the biosynthetic genes 31 – 33 . Multiple flavoenzymes were identified in the FST BGC from the marine-derived Micromonospora rosaria SCSIO N160 ( fls ) 28 .…”

Isolation and NMR Scaling Factors for the Structure Determination of Lobatolide H, a Flexible Sesquiterpene from Neurolaena lobata

“…To elucidate the absolute configuration and further verify the NMR results, TDDFT-ECD calculations [ 73 , 74 , 75 ] were performed on the MMFF conformers of the four possible isomers of 1. The initial conformers were re-optimized at the CAM-B3LYP/TZVP [ 76 ] PCM/MeCN level ( Table S40 ) and rotatory strength values were computed at four different levels similarly to the recently described lobatolides [ 24 ].…”

Hierarchical Titanium Silicalite-1 Zeolites Featuring an Ordered Macro–Meso–Microporosity for Efficient Epoxidations

“…Epoxides are important intermediates for fine chemicals and valuable commodities. − The catalytic epoxidation of alkenes catalyzed by titanium silicalite-1 (TS-1) zeolites using hydroperoxide as an oxidation leaves water as the only byproduct, which is a green pathway to produce epoxides. − This heterogeneous reaction follows a typical “seven-step” process, which includes (1) the diffusion of alkene molecules across the liquid–solid interface between the organic phase and TS-1 zeolites, (2) the diffusion of alkenes along the pores in TS-1 zeolites toward active Ti sites, (3–5) the adsorption, epoxidation of alkenes, and desorption of epoxides over active Ti sites, (6) the diffusion of epoxides in pores of TS-1 zeolites, and (7) the diffusion of epoxides across the solid–liquid interface into the organic phase. − The diffusion performance of the TS-1 zeolites is decisive for the whole epoxidation process. , Although TS-1 zeolites have been successfully applied as an efficient oxidation catalyst for small linear olefins, − they suffer severe intracrystalline diffusion in the epoxidation reaction with bulky substrates due to their relatively small pore size (∼0.55 nm). Consequently, bulky reactants are unable to enter into the micropores and diffuse to active sites, while large products generated on the active sites could not diffuse out of the micropores and may further convert into undesired products. − All these problems seriously restrict their applications to selective oxidation of bulky organic substrates.…”