Xylochemicals and where to find them

Geske L., Kauhl U., Saeed M., Schüffler A., Thines E., Efferth T., Opatz T.

The biological activities of shancigusin C (1) and bletistrin G (2), natural products isolated from orchids, are reported along with their first total syntheses. The total synthesis of shancigusin C (1) was conducted by employing the Perkin reaction to forge the central stilbene core, whereas the synthesis of bletistrin G (2) was achieved by the Wittig olefination followed by several regioselective aromatic substitution reactions. Both syntheses were completed by applying only renewable starting materials according to the principles of xylochemistry. The cytotoxic properties of shancigusin C (1) and bletistrin G (2) against tumor cells suggest suitability as a starting point for further structural variation.

Zhu H., Ali I., Hussain H., Hussain M., Wang X., Song X., Luo G., Zhang Z., Wang Z., Wang D.

• A coordination complexation method was used to separate cis-trans asarone. • The cis-trans isomers were extracted with ASE & selected with orthogonal testing. • The complexing agent can significantly increase the separation factor in HSCCC. • DFT analysis, formula derivation and UV-Vis spectra predicted the method. Acorus tatarinowii Schott is a traditional Chinese medicine used to treat memory and cognitive dysfunction. Because of their efficacy and lower toxic effects, research on α - and β -asarone, the phytoconstituents, has attracted attention owing to their remarkable pharmacological activities. Silver ion coordination complexation high-speed counter-current chromatography was used to separate these isomers from A. tatarinowii extract, coupled with accelerated solvent extraction. Accelerated solvent extraction parameters were investigated with single-factor and orthogonal testing. A two-phase solvent system composed of n -hexane-ethyl acetate-ethanol-water (2:1:2:1, v/v ) with 0.50 mol/L silver ions was selected for separation. From 2.0 g crude extract, 1.4 g of β -asarone and 0.09 g of α -asarone were obtained with purities over 98% by sequential sample loading in 20 h. The isolated compounds were identified by electrospray ionization mass spectrometry, 1 H and 13 C NMR. Silver ions significantly increased the separation factor and retention of the stationary phase. The chromatographic behavior indicated that cis -configuration was more strongly complexed with the silver ion. This was further demonstrated with the help of computational analysis. In conclusion, the established method could be employed to separate other cis - trans or E/Z isomers that form coordination complexes.

Tunç M.T., Koca İ.

Liu X., Bouxin F.P., Fan J., Budarin V.L., Hu C., Clark J.H.

“Lignin-first” biorefinery: Catalytic valorization of lignin provides a promising and attractive strategy for producing value-added phenolic monomers. The recent advances in catalytic depolymerization of technical lignin and reductive catalytic fractionation of protolignin are comprehensively summarized. The mechanism of condensation reactions and possible solutions are also discussed.

Ilmiawati A., Anggraini D., Syahbirin G., Rahayu D.U., Sugita P.

Sausage tree (Kigelia africana) is a medicinal plant of Bignoniaceae family which can be used as anticancer. Study on K. africana as an anticancer activity is still restricted to its crude extract while the structure of its active compound is still limited. On the other hand, K. africana in Indonesia has not been used as a medicine. It is only used as an ornamental plant because of its unique fruit shape. Therefore, it is interesting to conduct a research on isolation of active compounds from K. africana having anticancer activity. Simplicia of K. africana fruit was macerated in methanol and fractionated using vacuum liquid chromatography obtained 6 fractions (A-F). Fraction C was further fractionated using radial chromatography yielded 5 sub-fractions. Sub-fractions C3 and C4 were purified by preparative thin layer chromatography and obtained cinnamate derivative. Based on NMR and LC-MS spectral data, cinnamate derivative was identified as methyl ferulate. This study reported the isolation of methyl ferulate from K. africana which can be examined to its anticancer activity in further research.

Pomalaza G., Arango Ponton P., Capron M., Dumeignil F.

Catalytic conversion of ethanol is a promising technology for producing sustainable butadiene. This paper reviews the reaction and its catalysts, and discusses the challenges their development faces.

Zirbes M., Quadri L.L., Breiner M., Stenglein A., Bomm A., Schade W., Waldvogel S.R.

Lignin represents the largest renewable resource of aromatic moieties on earth and harbors a huge potential as a sustainable feedstock for the synthesis of biobased aromatic fine chemicals. Due to ...

Alsarraf J., Bilodeau J., Legault J., Simard F., Pichette A.

The preparation of bioactive molecules from biomass substrates is a relevant approach to replace fossil resources. The substitution patterns of natural products facilitate the access to polyfunctio...

Ouyang X., Huang X., Boot M.D., Hensen E.J.

Obtaining chemical building blocks from biomass is attractive for meeting sustainability targets. Herein, an effective approach was developed to convert the lignin part of woody biomass into phenol, which is a valuable base chemical. Monomeric alkylmethoxyphenols were obtained from pinewood, rich in guaiacol-type lignin, through Pt/C-catalyzed reductive depolymerization. In a second step, an optimized MoP/SiO2 catalyst was used to selectively remove methoxy groups in these lignin monomers to generate 4-alkylphenols, which were then dealkylated by zeolite-catalyzed transalkylation to a benzene stream. The overall yield of phenol based on the initial lignin content in pinewood was 9.6 mol %.

Pham T.T., Chen X., Söhnel T., Yan N., Sperry J.

A chitin-sourced 3-aminocyclopentenone building block is an effective platform for the diversity-oriented synthesis of nitrogen compounds in processes independent of Haber ammonia.

Amer H., Mimini V., Schild D., Rinner U., Bacher M., Potthast A., Rosenau T.

AbstractConiferyl alcohol is considered to be a potent antioxidant and a precursor of several bioactive products. In addition, it is a frequently used as a model compound in lignin chemistry. Coniferyl thiol is used analogously to study the sulfur chemistry in technical lignins. Coniferyl alcohol was synthesized in a large scale from commercially available ferulic acid by a mixed anhydride reduction method which affords high yields (84%) under very mild conditions and allows using sodium borohydride. The nucleophilic substitution of 4-O-acetylated coniferyl alcohol (3) with thioacetic acid in the presence of dimethylformamide (DMF) dineopentylacetal afforded 4-O-acetylated coniferyl thioacetate (5) in a 70% yield, which, in a 72% yield, was deprotected to the respective thiol (6). Both coniferyl alcohol and coniferyl thiol were comprehensively analytically characterized [one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) spectroscopy]. The presented approach renders the two model substances readily available on a gram scale and according to low-risk, environmentally compatible protocols.

Zhang C., Wang F.

In recent decades, research on lignin depolymerization and its downstream product transformation has drawn an enormous amount of attention from academia to industry worldwide, aiming at harvesting aromatic compounds from this abundant and renewable biomass resource. Although the lignin conversion can be traced back to the 1930s and various noncatalytic and catalytic methods have been explored to depolymerize lignin via direct lignin conversion research or lignin models conversion studies, the complexity of the lignin structure, various linkages, the high stability of lignin bonds, and the diverse fragments condensation process make lignin depolymerization to monomers a highly challenging task. For the potential practical utilization of lignin, compared with lignin conversion to liquid fuel with extra H2 consumption, maintaining the aromatic structure and preparing high-value aromatic chemicals from renewable lignin is more profitable. Therefore, lignin depolymerization to easy-to-handle aromatic monomers with acceptable conversion and selectivity is of great importance. In this article, we present our recent studies on lignin's catalytic conversion to aromatic chemicals. First, we introduce our research on protolignin depolymerization via a fragmentation-hydrogenolysis process in alcohol solvents. Then, focusing on the catalytic cleavage of lignin C-C and C-O bonds, we shed light on a recapitulative adjacent functional group modification (AFGM) strategy for the conversion of lignin models. AFGM strategy begins with the adjacent functional group modification of the target C-C or C-O bond to directly decrease the bond dissociation enthalpy (BDE) of targeted bonds or generate new substrate sites to introduce the cleavage reagent for further conversion. Subsequently, on the basis of these two concepts from AFGM, we summarize our strategies on lignin depolymerization, which highlight the effects of lignin structure, catalyst character, and reaction conditions on the efficiency of strategies. In short, the key point for lignin depolymerization to aromatics is promoting the lignin conversion and restraining the condensation. Compared with the complex research on direct lignin conversion, this bottom-up research approach, beginning with lignin model research, can make the conversion mechanism study clear and provide potential methods for the protolignin/technical lignin conversion. In addition, one of our perspectives for lignin utilization is that the products from lignin conversion can be used as monomers for artificial polymerization, such as the simple phenol (PhOH) and other potential acid compounds, or that lignin derivative molecules can be used to synthesize high-value synthetic building blocks.

Kühlborn J., Groß J., Opatz T.

This review highlights the utilization of biomass-derived building blocks in the total synthesis of natural products.

Lin C., Cheng S., Wu C., Chang S.

Indigenous cinnamon (Cinnamomum osmophloeum) is an endemic tree in Taiwan. The leaf essential oil is rich in trans-cinnamaldehyde, and its excellent antifungal activity has been reported. Since trans-cinnamaldehyde is a volatile compound, it is here evaluated for whether it is more effective via fumigant action. This study illustrates the antifungal action of trans-cinnamaldehyde against wood-decay fungi. Two ways that trans-cinnamaldehyde inhibits the growth of fungi, namely direct contact and fumigation, were examined using the agar dilution method (AD) and the inverted paper disc method (IPD). In addition, the amount of trans-cinnamaldehyde vapor in the headspace of the Petri dish was quantified using solid-phase microextraction and GC–MS. Antifungal results showed that the antifungal indices observed in the IPD method were clearly higher than those in the AD method, indicating that trans-cinnamaldehyde vapor had stronger antifungal activity. Results from the quantitative analysis also revealed that the amounts of trans-cinnamaldehyde vapor measured by the IPD method were significantly greater than those by the AD method. Accordingly, with higher amount of trans-cinnamaldehyde evaporated, stronger antifungal activity was observed. It is clear that the antifungal action of trans-cinnamaldehyde was primarily attributed to fumigation instead of direct contact.

Gonzalez‐Garcia R.A., McCubbin T., Turner M.S., Nielsen L.K., Marcellin E.

Native to propionibacteria, the Wood–Werkman cycle enables propionate production via succinate decarboxylation. Current limitations in engineering propionibacteria strains have redirected attention toward the heterologous production in model organisms. Here, we report the functional expression of the Wood–Werkman cycle in Escherichia coli to enable propionate and 1-propanol production. The initial proof-of-concept attempt showed that the cycle can be used for production. However, production levels were low (0.17 mM). In silico optimization of the expression system by operon rearrangement and ribosomal-binding site tuning improved performance by fivefold. Adaptive laboratory evolution further improved performance redirecting almost 30% of total carbon through the Wood–Werkman cycle, achieving propionate and propanol titers of 9 and 5 mM, respectively. Rational engineering to reduce the generation of byproducts showed that lactate (∆ldhA) and formate (∆pflB) knockout strains exhibit an improved propionate and 1-propanol production, while the ethanol (∆adhE) knockout strain only showed improved propionate production.

Liu Y., Markus J., Cheng H., Bernhardt P.V., Whittaker A.K., Blakey I., Williams C.M.

Neville J.C., Kieu C.N., Sperry J.

Millar S.B., Khachatryan H.N., Malmir M., Sperry J.

Curiel-Alegre S., de la Fuente-Vivas D., Khan A.H., García-Tojal J., Velasco-Arroyo B., Rumbo C., Soja G., Rad C., Barros R.

Persistent, aged hydrocarbons in soil hinder remediation, posing a significant environmental threat. While bioremediation offers an environmentally friendly and cost-effective approach, its efficacy for complex contaminants relies on enhancing pollutant bioavailability. This study explores the potential of immobilized bacterial consortia combined with biochar and rhamnolipids to accelerate bioremediation of aged total petroleum hydrocarbon (TPH)-contaminated soil. Previous research indicates that biochar and biosurfactants can increase bioremediation rates, while mixed consortia offer sequential degradation and higher hydrocarbon mineralization. The present investigation aimed to assess whether combining these strategies could further enhance degradation in aged, complex soil matrices. The bioaugmentation (BA) with bacterial consortium increased the TPHs degradation in aged soil (over 20% compared to natural attenuation - NA). However, co-application of BA with biochar and rhamnolipid higher did not show a statistically prominent synergistic effect. While biochar application facilitated the maintenance of hydrocarbon degrading bacterial consortium in soil, the present study did not identify a direct influence in TPHs degradation. The biochar application in contaminated soil contributed to TPHs adsorption. Rhamnolipid alone slightly increased the TPHs biodegradation with NA, while the combined bioaugmentation treatment with rhamnolipid and biochar increased the degradation between 27.5 and 29.8%. These findings encourage further exploration of combining bioaugmentation with amendment, like biochar and rhamnolipid, for remediating diverse environmental matrices contaminated with complex and aged hydrocarbons.

Swoboda A., Zwölfer S., Duhović Z., Bürgler M., Ebner K., Glieder A., Kroutil W.

Abstract5‐(Hydroxymethyl)furfural (HMF) is a key platform chemical derived from renewable biomass sources, holding great potential as starting material for the synthesis of valuable compounds, thereby replacing petrochemical‐derived counterparts. Among these valorised compounds, 2,5‐furandicarboxylic acid (FDCA) has emerged as a versatile building block. Here we demonstrate the biocatalytic synthesis of FDCA from HMF via a one‐pot three‐step oxidative cascade performed via two operative steps under mild reaction conditions employing two unspecific peroxygenases (UPOs) using hydrogen peroxide as the only oxidant. The challenge of HMF oxidation by UPOs is the chemoselectivity of the first step, as one of the two possible oxidation products is only a poor substrate for further oxidation. The unspecific peroxygenase from Marasmius oreades (MorUPO) was found to oxidize 100 mM of HMF to 5‐formyl‐2‐furoic acid (FFCA) with 95 % chemoselectivity. In the sequential one‐pot cascade employing MorUPO (TON up to 13535) and the UPO from Agrocybe aegerita (AaeUPO, TON up to 7079), 100 mM of HMF were oxidized to FDCA reaching up to 99 % conversion and yielding 861 mg isolated pure crystalline FDCA, presenting the first example of a gram scale biocatalytic synthesis of FDCA involving UPOs.

Šachlevičiūtė U., Kleiziene N., Bieliauskas A., Šačkus A., Opatz T.

A synthesis of pyrrolo[2,1-a]isoquinolines based on intramolecular condensation of an enaminone intermediate obtained by C-acylation of an N-alkylated 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinolinium salt was developed.

Geske L., Baier J., Boulos J.C., Efferth T., Opatz T.

Bachmann J., Helbig A., Crumbach M., Krummenacher I., Braunschweig H., Helten H.

Merging furan rings with 1,2,7-oxa- and -azadiborepins. This modular synthesis proceeds through a reversible ring-opening process and furnishes the novel heteropolyaromatic compounds from a common precursor. The tricyclic systems are overall aromatic, and weak aromaticity in the diboron heterocycles favors π electron delocalization over the bifuran unit. The π-conjugated system is easily extended through the α-positions of the furan rings.

Pollok D., Großmann L.M., Behrendt T., Opatz T., Waldvogel S.R.

Amaryllidaceae alkaloids appeal to organic chemists with their attractive structures and their impressive antitumor and acetylcholinesterase inhibitory properties. We demonstrate a highly versatile access to this family of natural products. A general protocol with high yields in a sustainable electro-organic key transformation on a metal-free anode to spirodienones facilitates functionalization to the alkaloids. The biomimetic syntheses start with the readily available, inexpensive biogenic starting materials methyl gallate, O-methyl tyramine, and vanillin derivatives. Through known dynamic resolutions, this technology provides access to both enantiomeric series of (epi-)martidine, (epi-)crinine, siculine, and galantamine, clinically prescribed for the treatment of Alzheimer's disease.

Lood K., Tikk T., Krüger M., Schmidt B.

Four combinations of type-I olefins isoeugenol and 4-hydroxy-3-methoxystyrene with type-II olefins acrolein and crotonaldehyde were investigated in cross-metathesis (CM) reactions. While both type-I olefins are suitable CM partners for this transformation, we observed synthetically useful conversions only with type-II olefin crotonaldehyde. For economic reasons, isoeugenol, a cheap xylochemical available from renewable lignocellulose or from clove oil, is the preferred type-I CM partner. Nearly quantitative conversions to coniferyl aldehyde by the CM reaction of isoeugenol and crotonaldehyde can be obtained at ambient temperature without a solvent or at high substrate concentrations of 2 mol·L-1 with the second-generation Hoveyda-Grubbs catalyst. Under these conditions, the ratio of reactants can be reduced to 1:1.5 and catalyst loadings as low as 0.25 mol % are possible. The high reactivity of the isoeugenol/crotonaldehyde combination in olefin metathesis reactions was demonstrated by a short synthesis of the natural product 7-methoxywutaifuranal, which was obtained from isoeugenol in a 44% yield over five steps. We suggest that the superior performance of crotonaldehyde in the CM reactions investigated can be rationalized by "methylene capping", i.e., the steric stabilization of the propagating Ru-alkylidene species.