Synthesis of a chiral dinuclear Cu(II)-benzothiazolamine complex: evidence of cuprophilic interaction in its structure and exploration of its electrochemical properties and catalytic performance.

The synthesis of a chiral dinuclear [Cu(OAc)2(L1)]2 complex (A) and its analogues Cu(OAc)2(L1)2 (B), Cu(OAc)2(L1)PPh3 (C), CuBr(L1)PPh3 (D), and Cu(OAc)2(L2) (E) is described. The X-ray structure of A reveals a cuprophilic interaction (2.65 Å) and shows that L1 behaves as a monodentate ligand. The stereogenic centre in L1 aligns the NH group to form non-covalent interactions with the paddle-wheel acetate groups at variable distances (2.4-2.5 Å and 2.2-2.7 Å). Thermogravimetric analysis confirmed our hypothesis that two equivalents of L1 (B) or a combination of L1 and PPh3 (C) would disrupt the cuprophilic interaction. All complexes, except D, showed irreversible redox waves by cyclic voltammetry. Complexes C and E have lower oxidative peaks (at 10 V s-1) than complex A between +0.40 and +0.60 V. This highlights the influence of ligand(s) on the redox behaviour of Cu(II) complexes. The significance of this electrochemical behaviour was evident in the Chan-Lam (CL) coupling reaction, where 2.5 mol% of A successfully facilitated the formation of a C-N bond. This study showcased the structure, thermal stability, electrochemical properties and catalytic performance of a chiral dinuclear copper(II)-benzothiazolamine complex.

Expeditious access to cis-ß-aryl, γ-alkyl disubstituted (±)-γ-butyrolactones via nickel-hydride catalysis.

The 1,4-reduction of ß- and γ-substituted butenolides using 5 mol% of NiCl2·6H2O and NaBH4 in MeOH for rapid access to cis-ß,γ-disubstituted γ-butyrolactones is described. The reaction was selective for cis-products, which were obtained in good to excellent yields. This study showcased the influence of steric hindrance and angle strain on the diastereoselectivity outcome of conjugate reductions facilitated by in situ generated nickel-hydride.

An expedient copper-catalysed asymmetric synthesis of γ-lactones and γ-lactams. Application to the synthesis of lucidulactone A.

The parent Josiphos ligand gave excellent ee values (95-99%) and good yields (60-97%) in the copper-catalysed asymmetric conjugate reduction of ß-aryl α,ß-unsaturated lactones and lactams with PMHS. The substrates were obtained from stereospecific copper-catalysed addition of arylboronic acids to alkynoates followed by deprotection and cyclisation. The acyclic lactam precursors also underwent reduction with good ee values (83-85%) and yields (79-95%). Application of this asymmetric reduction methodology included the synthesis of natural product lucidulactone A.

Bacterial Catabolism of ß-Hydroxypropiovanillone and ß-Hydroxypropiosyringone Produced in the Reductive Cleavage of Arylglycerol-ß-Aryl Ether in Lignin.

Sphingobium sp. strain SYK-6 converts four stereoisomers of arylglycerol-ß-guaiacyl ether into achiral ß-hydroxypropiovanillone (HPV) via three stereospecific reaction steps. Here, we determined the HPV catabolic pathway and characterized the HPV catabolic genes involved in the first two steps of the pathway. In SYK-6 cells, HPV was oxidized to vanilloyl acetic acid (VAA) via vanilloyl acetaldehyde (VAL). The resulting VAA was further converted into vanillate through the activation of VAA by coenzyme A. A syringyl-type HPV analog, ß-hydroxypropiosyringone (HPS), was also catabolized via the same pathway. SLG_12830 (hpvZ), which belongs to the glucose-methanol-choline oxidoreductase family, was isolated as the HPV-converting enzyme gene. An hpvZ mutant completely lost the ability to convert HPV and HPS, indicating that hpvZ is essential for the conversion of both the substrates. HpvZ produced in Escherichia coli oxidized both HPV and HPS and other 3-phenyl-1-propanol derivatives. HpvZ localized to both the cytoplasm and membrane of SYK-6 and used ubiquinone derivatives as electron acceptors. Thirteen gene products of the 23 aldehyde dehydrogenase (ALDH) genes in SYK-6 were able to oxidize VAL into VAA. Mutant analyses suggested that multiple ALDH genes, including SLG_20400, contribute to the conversion of VAL. We examined whether the genes encoding feruloyl-CoA synthetase (ferA) and feruloyl-CoA hydratase/lyase (ferB and ferB2) are involved in the conversion of VAA. Only FerA exhibited activity toward VAA; however, disruption of ferA did not affect VAA conversion. These results indicate that another enzyme system is involved in VAA conversion.IMPORTANCE Cleavage of the ß-aryl ether linkage is the most essential process in lignin biodegradation. Although the bacterial ß-aryl ether cleavage pathway and catabolic genes have been well documented, there have been no reports regarding the catabolism of HPV or HPS, the products of cleavage of ß-aryl ether compounds. HPV and HPS have also been found to be obtained from lignin by chemoselective catalytic oxidation by 2,3-dichloro-5,6-dicyano-1,4-benzoquinone/tert-butyl nitrite/O2, followed by cleavage of the ß-aryl ether with zinc. Therefore, value-added chemicals are expected to be produced from these compounds. In this study, we determined the SYK-6 catabolic pathways for HPV and HPS and identified the catabolic genes involved in the first two steps of the pathways. Since SYK-6 catabolizes HPV through 2-pyrone-4,6-dicarboxylate, which is a building block for functional polymers, characterization of HPV catabolism is important not only for understanding the bacterial lignin catabolic system but also for lignin utilization.

Synthesis of the natural product descurainolide and cyclic peptides from lignin-derived aromatics.

Alternative sources of potential feedstock chemicals are of increasing importance as the availability of oil decreases. The biopolymer lignin is viewed as a source of useful mono-aromatic compounds as exemplified by the industrial scale production of vanillin from this biomass. Alternative lignin-derived aromatics are available in pure form but to date examples of the use of these types of compounds are rare. Here we address this issue by reporting the conversion of an aromatic keto-alcohol to the anti- and syn-isomers of Descurainolide A. The key step involves a rhodium-catalyzed allylic substitution reaction. Enantio-enriched allylic alcohols were generated via an isothiourea-catalyzed kinetic resolution enabling access to both the (2R,3R) and (2S,3S) enantiomers of anti-Descurainolide A. In addition we show that the lignin-derived keto-alcohols can be converted into unnatural amino acid derivatives of tyrosine. Finally, these amino acids were incorporated into cyclic peptide scaffolds through the use of both chemical and an enzyme-mediated macrocylisation.

The synthesis and analysis of lignin-bound Hibbert ketone structures in technical lignins.

Understanding the structure of technical lignins resulting from acid-catalysed treatment of lignocellulosic biomass is important for their future applications. Here we report an investigation into the fate of lignin under acidic aqueous organosolv conditions. In particular we examine in detail the formation and reactivity of non-native Hibbert ketone structures found in isolated organosolv lignins from both Douglas fir and beech woods. Through the use of model compounds combined with HSQC, HMBC and HSQC-TOCSY NMR experiments we demonstrate that, depending on the lignin source, both S and G lignin-bound Hibbert ketone units can be present. We also show that these units can serve as a source of novel mono-aromatic compounds following an additional lignin depolymerisation reaction.

Isothiourea-Catalysed Acylative Kinetic Resolution of Aryl-Alkenyl (sp2 vs. sp2 ) Substituted Secondary Alcohols.

The non-enzymatic acylative kinetic resolution of challenging aryl-alkenyl (sp2 vs. sp2 ) substituted secondary alcohols is described, with effective enantiodiscrimination achieved using the isothiourea organocatalyst HyperBTM (1 mol %) and isobutyric anhydride. The kinetic resolution of a wide range of aryl-alkenyl substituted alcohols has been evaluated, with either electron-rich or naphthyl aryl substituents in combination with an unsubstituted vinyl substituent providing the highest selectivity (S=2-1980). The use of this protocol for the gram-scale (2.5 g) kinetic resolution of a model aryl-vinyl (sp2 vs. sp2 ) substituted secondary alcohol is demonstrated, giving access to >1 g of each of the product enantiomers both in 99:1 e.r.

Isolation of functionalized phenolic monomers through selective oxidation and C-O bond cleavage of the ß-O-4 linkages in lignin.

Functionalized phenolic monomers have been generated and isolated from an organosolv lignin through a two-step depolymerization process. Chemoselective catalytic oxidation of ß-O-4 linkages promoted by the DDQ/tBuONO/O2 system was achieved in model compounds, including polymeric models and in real lignin. The oxidized ß-O-4 linkages were then cleaved on reaction with zinc. Compared to many existing methods, this protocol, which can be achieved in one pot, is highly selective, giving rise to a simple mixture of products that can be readily purified to give pure compounds. The functionality present in these products makes them potentially valuable building blocks.