Regioselective aromatic <i>O</i>-demethylation with an artificial P450BM3 peroxygenase system

Jiang, Yihui; Wang, Chunlan; Ma, Ning; Chen, Jie; Liu, Chuanfei; Wang, Fang; Xu, Jiakun; Cong, Zhiqi

doi:10.1039/d0cy00241k

Cited by 37 publications

(56 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 7 , 8 Nevertheless, alternative approaches toward milder and selective demethylation are demanded. 10 , 11 O -Demethylation of methyl aryl ethers may also be achieved using biocatalysts: 11 − 14 For example, oxidative enzymes 15 − 18 such as di- and monooxygenases 19 − 24 and fungal peroxygenases 25 − 27 catalyze the O -demethylation by using molecular oxygen or hydrogen peroxide as reagents. These enzymes are known for the detoxification of organic compounds, 25 degradation of lignin, 21 and the biosynthesis of secondary metabolites.…”

Section: Introductionmentioning

confidence: 99%

Oxygen-Free Regioselective Biocatalytic Demethylation of Methyl-phenyl Ethers via Methyltransfer Employing Veratrol-O-demethylase

et al. 2020

View full text Add to dashboard Cite

The cleavage of aryl methyl ethers is a common reaction in chemistry requiring rather harsh conditions; consequently, it is prone to undesired reactions and lacks regioselectivity. Nevertheless, O -demethylation of aryl methyl ethers is a tool to valorize natural and pharmaceutical compounds by deprotecting reactive hydroxyl moieties. Various oxidative enzymes are known to catalyze this reaction at the expense of molecular oxygen, which may lead in the case of phenols/catechols to undesired side reactions (e.g., oxidation, polymerization). Here an oxygen-independent demethylation via methyl transfer is presented employing a cobalamin-dependent veratrol- O -demethylase (vdmB). The biocatalytic demethylation transforms a variety of aryl methyl ethers with two functional methoxy moieties either in 1,2-position or in 1,3-position. Biocatalytic reactions enabled, for instance, the regioselective monodemethylation of substituted 3,4-dimethoxy phenol as well as the monodemethylation of 1,3,5-trimethoxybenzene. The methyltransferase vdmB was also successfully applied for the regioselective demethylation of natural compounds such as papaverine and rac -yatein. The approach presented here represents an alternative to chemical and enzymatic demethylation concepts and allows performing regioselective demethylation in the absence of oxygen under mild conditions, representing a valuable extension of the synthetic repertoire to modify pharmaceuticals and diversify natural products.

show abstract

Section: Introductionmentioning

confidence: 99%

Oxygen-Free Regioselective Biocatalytic Demethylation of Methyl-phenyl Ethers via Methyltransfer Employing Veratrol-O-demethylase

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Since the methyl ether group is widely found in nature, [5] a variety of enzymes are able to transform this moiety such as (i) monooxygenases, [6] (ii) peroxygenases, [7] (iii) dehydratases as observed for PEG degradation [8] and (iv) methyltransferases [9] . Mostly, the methyl ether groups are cleaved by P450 enzymes at the expense of NAD(P)H and molecular oxygen by C−H oxidation at the carbon next to the ether oxygen, resulting in a hemiacetal, which then decomposes [6a, 7c, 10] . However, the oxidative conditions may cause various challenges; [7c, 11] e.g., when catechol is the target product, the presence of molecular oxygen may initiate undesired follow‐up reactions (such as polymerization, autooxidation, quinone formation).…”

Section: Methodsmentioning

confidence: 99%

Thiols Act as Methyl Traps in the Biocatalytic Demethylation of Guaiacol Derivatives

et al. 2021

View full text Add to dashboard Cite

Demethylating methyl phenyl ethers is challenging, especially when the products are catechol derivatives prone to follow-up reactions. For biocatalytic demethylation, monooxygenases have previously been described requiring molecular oxygen which may cause oxidative side reactions. Here we show that such compounds can be demethylated anaerobically by using cobalamin-dependent methyltransferases exploiting thiols like ethyl 3-mercaptopropionate as a methyl trap. Using just two equivalents of this reagent, a broad spectrum of substituted guaiacol derivatives were demethylated, with conversions mostly above 90 %. This strategy was used to prepare the highly valuable antioxidant hydroxytyrosol on a one-gram scale in 97 % isolated yield.

show abstract

“…As alternatives to natural enzymes, articial enzymes have received much attention for decades due to their potential applications, including in the environment. [14][15][16][17][18][19][20][21] With the advantages of high-yield of overexpression in E. coli cells, myoglobin (Mb), an O 2 carrier, has been favored for rational design of articial enzymes with multiple functions. 22 For example, Lu and colleagues rationally designed articial hemecopper oxidases and nitric oxide reductases by creating Cu B or Fe B metal-binding site in Mb.…”

Section: Introductionmentioning

confidence: 99%

Efficient biodegradation of malachite green by an artificial enzyme designed in myoglobin

Xiang

Liu

et al. 2021

RSC Adv.

View full text Add to dashboard Cite

show abstract

Regioselective aromatic O-demethylation with an artificial P450BM3 peroxygenase system

Abstract: Highly regioselective O-demethylation of aromatic ethers related to the bioconversion of lignin was achieved by the H2O2-dependent engineered P450BM3 enzymes with assistance of a dual-functional small molecule (DFSM) for the first time.

Cited by 37 publications

References 36 publications

Oxygen-Free Regioselective Biocatalytic Demethylation of Methyl-phenyl Ethers via Methyltransfer Employing Veratrol-O-demethylase

Oxygen-Free Regioselective Biocatalytic Demethylation of Methyl-phenyl Ethers via Methyltransfer Employing Veratrol-O-demethylase

Thiols Act as Methyl Traps in the Biocatalytic Demethylation of Guaiacol Derivatives

Efficient biodegradation of malachite green by an artificial enzyme designed in myoglobin

Contact Info

Product

Resources

About