Oxygen-directed methylation is a ubiquitous tailoring reaction in natural product pathways catalysed by O-methyltransferases (OMTs). Promiscuous OMT biocatalysts are thus a valuable asset in the toolkit for sustainable synthesis and optimization of known bioactive scaffolds for drug development. Here, we characterized the enzymatic properties and substrate scope of two bacterial OMTs from Desulforomonas acetoxidans and Streptomyces avermitilis and determined their crystal structures. Both OMTs methylated a wide range of catechol-like substrates, including flavonoids, coumarins, hydroxybenzoic acids, and their respective aldehydes, an anthraquinone and an indole. One enzyme also accepted a steroid. The product range included pharmaceutically relevant compounds such as (iso)fraxidin, iso(scopoletin), chrysoeriol, alizarin 1-methyl ether, and 2-methoxyestradiol. Interestingly, certain non-catechol flavonoids and hydroxybenzoic acids were also methylated. This study expands the knowledge on substrate preference and structural diversity of bacterial catechol OMTs and paves the way for their use in (combinatorial) pathway engineering.
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http://dx.doi.org/10.1002/cbic.202300076 | DOI Listing |
J Am Chem Soc
January 2025
Institute of Organic Chemistry, University of Leipzig, 04103 Leipzig, Germany.
The enantioselective synthesis of 1,4-dicarbonyl compounds continues to pose a significant challenge in organic synthesis, and a catalytic process which generates two adjacent stereogenic centers with full stereochemical control is lacking until now. The 1,4-relationship of the functional groups requires an Umpolung strategy as one of the α-carbonyl positions has to be inverted into an electrophilic center to react with a normal enolate. We report herein the highly enantio- and diastereoselective addition of silyl ketene acetals toward electrophilic 1-azaallyl cations to furnish chiral 4-hydrazonoesters, which are masked 1,4-dicarbonyl compounds.
View Article and Find Full Text PDFLangmuir
January 2025
Department of Chemistry, Chungnam National University, Daejeon 34134, Republic of Korea.
Bioinspired coatings that mimic the adhesive properties of mussels have received considerable attention for surface modification applications. While polydopamine chemistry has been widely used to develop functional coatings, 3,4-dihydroxyphenyl-l-alanine (l-DOPA), a key component of mussel adhesive proteins, has received less attention because, compared to dopamine, it is relatively difficult to form effective coatings on solid substrates in mildly alkaline solutions. Although several methods have been explored to improve the efficiency of l-DOPA coatings, there is still a need to expand the l-DOPA-based surface chemistry.
View Article and Find Full Text PDFJ Org Chem
January 2025
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Dual photoredox and copper-catalyzed remote asymmetric C(sp)-H alkylation of hydroxamic acid derivatives with glycine derivatives via a 1,5-hydrogen transfer (1,5-HAT) process has been realized. The reaction was characterized by redox-neutral and mild conditions, good yields, excellent enantioselectivity, and broad substrate scope. This protocol provides a straightforward and efficient strategy to prepare highly valuable enantioenriched noncanonical α-amino acids.
View Article and Find Full Text PDFChem Asian J
January 2025
Northwest University, Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, Department of Chemistry & Materials Science,, 1 Xuefu Ave., Guodu Education and Hi-Tech Industries Zone,, Chang'an District, 710127, Xi'an, CHINA.
Herein, we describe a protocol for Brønsted acid-catalyzed regioselective coupling of azoles such as pyrazoles, 1,2,3-triazole, 1,3,4-triazole, benzotriazole, indazole and tetrazole, to cyclobutenes. These azoles could be directly coupled with various arylcyclobutenes with high site-selectivity, offering a distinct entry to more functionalized cyclobutanes. The usage of inexpensive TsOH•H2O catalyst, broad substrate scope, and open-air conditions make this protocol practically viable.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
January 2025
Tianjin University, Department of Chemistry, #92, Weijin Road, Nankai District, Department of Chemistry, School of Science, Tianjin University, 300072, Tianjin, CHINA.
Electrochemical reductive deuteration of nitriles is a promising strategy for synthesizing deuterated amines with D2O as the deuterated source. However, this reaction suffers from high overpotentials owing to the sluggish D2O dissociation kinetics and high thermodynamic stability of the C≡N triple bond. Here, low-coordinated copper (LC-Cu) is designed to decrease the overpotential for the electrosynthesis of the precursor of Melatonin-d4, 5-methoxytryptamine-d4, by 100 mV with a 68% yield (Faraday efficiency), which is 4 times greater than that of high-coordinated copper (HC-Cu).
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