Coupling Of Phenols Research Articles

ChemInform Abstract: Metal‐Free [3 + 2] Oxidative Coupling of Phenols with Alkenes: Synthesis of Dihydrobenzofurans.

AbstractAn environmentally benign and metal‐free [3+2]‐cycloaddition of phenols and styrenes with sodium persulfate as an oxidant affords dihydrobenzofurans.

More than just recruitment: the X-domain influences catalysis of the first phenolic coupling reaction in A47934 biosynthesis by Cytochrome P450 StaH.

Glycopeptide antibiotic biosynthesis involves a complex cascade of reactions centred on a non-ribosomal peptide synthetase and modifiying proteins acting in trans, such as Cytochrome P450 enzymes. These P450s are responsible for cyclisation of the peptide via cross-linking aromatic amino acid side chains, which are a hallmark of the glycopeptide antibiotics. Here, we analysed the first cyclisation reaction in the biosynthesis of the glycopeptide antibiotic A47934. Our results demonstrate that the P450 StaH is recruited to the NRPS machinery through interaction with the X-domain present in the last A47934 NRPS module. We determined the crystal structure of StaH and showed that it is responsible for the first cyclisation in A47934 biosynthesis and additionally exhibits flexible substrate specificity. Our results further point out that the X-domain has an impact on the efficiency of the in vitro cyclisation reaction: hybrid PCP-X constructs obtained by domain exchange between A47934 and teicoplanin biosynthesis NRPS modules reveal that the X-domain from A47934 leads to decreased P450 activity and alternate stereochemical preference for the substrate peptide. We determined that a tight interaction between StaH and the A47934 X-domain correlates with decreased in vitro P450 activity: this highlights the need for glycopeptide antibiotic cyclisation to be a dynamic system, with an overly tight interaction interfering with substrate turnover in vitro.

ChemInform Abstract: The Coupling Reactions of Aryl Halides and Phenols Catalyzed by Palladium and MOP‐Type Ligands.

AbstractOptimized reactions conditions are developed for the Pd‐catalyzed coupling of aryl halides and phenols.

ChemInform Abstract: Palladium‐Catalyzed Reductive Coupling of Phenols with Anilines and Amines: Efficient Conversion of Phenolic Lignin Model Monomers and Analogues to Cyclohexylamines.

AbstractA wide range of secondary and tertiary substituted cyclohexylamines are conveniently obtained using cheap and safe sodium formate as hydrogen source.

Cytochrome P450-catalyzed regio- and stereoselective phenol coupling of fungal natural products.

For almost 100 years, phenoxy radical coupling has been known to proceed in nature. Because of the linkage of their molecular halves (regiochemistry) and the configuration of the biaryl axis (stereochemistry), biaryls are notoriously difficult to synthesize. Whereas the intramolecular enzymatic coupling has been elucidated in detail for several examples, the bimolecular intermolecular coupling could not be assigned to one single enzyme in the biosynthesis of axially chiral biaryls. As these transformations often take place regio- and stereoselectively, enzyme-catalyzed control is reasonable. We now report the identification and expression of fungal cytochrome P450 enzymes that catalyze regio- and stereoselective intermolecular phenol couplings. The cytochrome P450 enzyme KtnC from the kotanin biosynthetic pathway of Aspergillus niger was expressed in Saccharomyces cerevisiae. The recombinant cells catalyzed the coupling of the monomeric coumarin 7-demethylsiderin both regio- and stereoselectively to the 8,8'-dimer P-orlandin, a precursor of kotanin. The sequence information obtained from the kotanin biosynthetic gene cluster was used to identify in silico a similar gene cluster in the genome of Emericella desertorum, a producer of desertorin A, the 6,8'-regioisomer of orlandin. The cytochrome P450 enzyme DesC was also expressed in S. cerevisiae and was found to regio- and stereoselectively catalyze the coupling of 7-demethylsiderin to M-desertorin A. Our results show that fungi use highly specific cytochrome P450 enzymes for regio- and stereoselective phenol coupling. The enzymatic activities of KtnC and DesC are relevant for an understanding of the mechanism of this important biosynthetic step. These results suggest that bimolecular phenoxy radical couplings in nature can be catalyzed by phenol-coupling P450 heme enzymes, which might also apply to the plant kingdom.

Injectable Degradation-Resistant Hyaluronic Acid Hydrogels Cross-Linked via the Oxidative Coupling of Green Tea Catechin.

The oxidative coupling of phenols by horseradish peroxidase (HRP) is widely utilized to cross-link polymer-phenol conjugates for hydrogel formation. Phenols containing one aromatic ring are most commonly used, and the addition of hydrogen peroxide (H2O2) is an indispensable step in catalyzing the enzymatic reaction. We describe here a hydrogel composed of polyphenol as the cross-linking moiety. (-)-Epigallocatechin-3-gallate (EGCG), a green tea catechin, was conjugated to hyaluronic acid (HA) to form HA-EGCG conjugates. Addition of HRP to a solution of HA-EGCG conjugates at pH 7.4 induced gelation in 7 min. Notably, the addition of exogenous H2O2 was not required, as H2O2 was generated via EGCG autoxidation. Moreover, cross-linking between HA-EGCG conjugates occurred in situ through EGCG quinone formation, even when no HRP was added. This approach of forming hydrogels circumvented the safety concern associated with HRP due to its plant origin. Furthermore, the EGCG moieties endowed the hydrogels with resistance toward hyaluronidase-mediated degradation in vivo.

Nickel- and Palladium-Catalyzed Coupling of Aryl Fluorosulfonates with Aryl Boronic Acids Enabled by Sulfuryl Fluoride

Herein are reported examples of the nickel- and palladium-catalyzed cross-coupling of aryl fluorosulfonates and aryl boronic acids. These reactions occur in good to excellent yields under mild conditions with excellent functional group compatibility employing either Pd(OAc)2 and inexpensive PPh3 or the inexpensive and readily available NiCl2(PCy3)2. Importantly, the in situ conversion of phenol derivatives to the corresponding aryl fluorosulfonate by reaction with sulfuryl fluoride and a base and subsequent cross-coupling to form biaryls in a single pot are described. The combination of inexpensive sulfuryl fluoride and efficient catalysts reported in these methodologies will enable economical Suzuki coupling of phenols in pharmaceutical and agrochemical processes.

Vinylation of Unprotected Phenols Using a Biocatalytic System.

Readily available substituted phenols were coupled with pyruvate in buffer solution under atmospheric conditions to afford the corresponding para-vinylphenol derivatives while releasing only one molecule of CO2 and water as the by-products. This transformation was achieved by designing a biocatalytic system that combines three biocatalytic steps, namely the C-C coupling of phenol and pyruvate in the presence of ammonia, which leads to the corresponding tyrosine derivative, followed by deamination and decarboxylation. The biocatalytic transformation proceeded with high regioselectivity and afforded exclusively the desired para products. This method thus represents an environmentally friendly approach for the direct vinylation of readily available 2-, 3-, or 2,3-disubstituted phenols on preparative scale (0.5 mmol) that provides vinylphenols in high yields (65-83 %).

Vinylation of Unprotected Phenols Using a Biocatalytic System

AbstractReadily available substituted phenols were coupled with pyruvate in buffer solution under atmospheric conditions to afford the corresponding para‐vinylphenol derivatives while releasing only one molecule of CO2 and water as the by‐products. This transformation was achieved by designing a biocatalytic system that combines three biocatalytic steps, namely the CC coupling of phenol and pyruvate in the presence of ammonia, which leads to the corresponding tyrosine derivative, followed by deamination and decarboxylation. The biocatalytic transformation proceeded with high regioselectivity and afforded exclusively the desired para products. This method thus represents an environmentally friendly approach for the direct vinylation of readily available 2‐, 3‐, or 2,3‐disubstituted phenols on preparative scale (0.5 mmol) that provides vinylphenols in high yields (65–83 %).

ChemInform Abstract: Synthesis of 2‐Acylphenol and Flavene Derivatives from the Ruthenium‐Catalyzed Oxidative C—H Acylation of Phenols with Aldehydes.

AbstractThe cationic ruthenium hydride complex catalyzes the oxidative C‐H coupling of phenols with aldehydes to furnish 2‐acylphenols, whereas the reaction of phenols with α,β‐unsaturated aldehydes affords flavene derivatives selectively.

ChemInform Abstract: The Quest for an Oxidative Coupling of Phenols and Indoles Towards Benzofuroindolines: A Two‐Stage Approach

AbstractReview: [14 refs.

4′‐O‐Methylnorbelladine feeding enhances galanthamine and lycorine production by Leucojum aestivum L. shoot cultures

Galanthamine and lycorine are Amaryllidaceae alkaloids that exhibit a wide range of pharmacological activities. Organic synthesis and plant extraction are the two main commercial sources of galanthamine. Since total organic synthesis is low yielding and complex, and the harvesting of plant biomass is causing wild plant depletion, in vitro cultures offer an alternative approach. Amaryllidaceae alkaloids can be regarded as derivatives of the common precursor 4′‐O‐methylnorbelladine via intramolecular oxidative phenol coupling. The aim of this work was to enhance the biosynthetic pathway of these alkaloids using in vitro techniques. The precursor 4′‐O‐methylnorbelladine was incorporated into the liquid medium of Leucojum aestivum shoot cultures at different concentrations (0, 0.05, 0.1, or 0.2 g/L). The cultures were conducted for various periods of time (15, 30, and 40 days). After alkaloid extraction and according to LC‐ESI‐MS analysis, the precursor highly stimulated the biosynthesis of both galanthamine (0.5 mg/g dry weight [DW], V/S 0.01 mg/g DW in the control sample, i.e. without precursor) and lycorine (0.2 mg/g DW, V/S 0.04 mg/g DW in the control sample) after its biotransformation by the shoot cultures. The optimal culture conditions for the production of both alkaloids were 0.1 g/L of precursor and 15 days of culture.

Metal-Free [3+2] Oxidative Coupling of Phenols with Alkenes: Synthesis of Dihydrobenzofurans

Herein, we demonstrated a benign and metal-free [3+2]-cycloaddition reaction using simple and readily available phenols and styrenes as substrates and sodium persulfate as an inexpensive and environmentally friendly oxidant for the direct synthesis of dihydrobenzofurans. This methodology was applied to the synthesis of corsifuran A in a single step.

ChemInform Abstract: Phenol and Aniline Oxidative Coupling with Alkenes by Using Hypervalent Iodine Dimer for the Rapid Access to Dihydrobenzofurans and Indolines.

AbstractThe highly reactive hypervalent iodine dimer [Ph(CF3COO)I]‐O‐[I(OCOCF3)Ph] is shown to promote the oxidative phenolic coupling with styrenes to afford different benzofuran derivatives.

ChemInform Abstract: Efficient Microwave Method for the Oxidative Coupling of Phenols.

AbstractAn efficient protocol for the oxidative coupling of phenols and naphthols is developed and compared with other oxidative coupling methodologies.

Biomimetic Total Syntheses of (+)-Dihydrolyfoline and (-)-5-epi-Dihydrolyfoline.

The first asymmetric total syntheses of (+)-dihydrolyfoline and (-)-5-epi-dihydrolyfoline have been achieved in five and six steps with 4.6% and 14% overall yields, respectively, in which the chiral biaryl axes were constructed in a highly regioselective and stereoselective manner via a biogenetic enzymatic oxidative couplings of phenols, and the requisite quinolizidinone cores were prepared by an enzymatic Mannich reaction.

ChemInform Abstract: Direct Oxidative Coupling of N‐Acetyl Indoles and Phenols for the Synthesis of Benzofuroindolines Related to Phalarine.

AbstractA novel direct oxidative [3 + 2] coupling of phenols and indoles to give a regioselective formation of benzofuro[3,2‐b]indolines (III) and (V), representing the phalarine core, is developed.

ChemInform Abstract: Recent Advances in Enantioselective Vanadium‐Catalyzed Transformations

AbstractReview: 155 refs.

Biomimetic synthesis of dendridine A.

Biomimetic synthesis of the bisindole natural product dendridine A is reported. Although attempts to install the hindered biaryl bond by oxidative phenolic coupling of the 7-hydroxytryptamine 6 gave the undesired ortho-ortho product, a Scholl-type oxidative coupling of the 7-isopropoxytryptamine 9 with molybdenum pentachloride proceeded through the desired para-para pathway, installing the entire carbon framework of dendridine A.

Synthesis of 2-Acylphenol and Flavene Derivatives from the Ruthenium-Catalyzed Oxidative C-H Acylation of Phenols with Aldehydes.

The cationic ruthenium hydride complex [(C6H6)(PCy3)(CO)RuH]+BF4- has been found to be an effective catalyst for the oxidative C-H coupling reaction of phenols with aldehydes to give 2-acylphenol compounds. The coupling of phenols with α,β-unsaturated aldehydes selectively gives the flavene derivatives. The catalytic method mediates direct oxidative C-H coupling of phenol and aldehyde substrates without using any metal oxidants or forming wasteful byproducts.