Sustainable pathways to bio-based amines via the 'hydrogen borrowing' strategy

The reduction of society’s dependence on fossil fuels and a gradual shift towards the use of renewables is of prime importance. Despite the considerable efforts that have been made to the introduction of novel catalytic methodologies that convert renewable resources to fuels or bio-based platform chemicals, the development of systematic strategies for the synthesis of amines - centrally important compounds in the bulk and fine chemical industry - from renewables, especially via waste-free catalytic routes, has not received due attention yet.This thesis outlines ample possibilities of using a variety of biomass sources for the synthesis of the high-value chemicals demonstrating the potential of renewable feedstocks as viable replacements for currently used fossil fuels. More specifically, it discloses the development of novel catalytic methods that enable the formation of value-added amines from readily available aliphatic and aromatic alcohol intermediates generated by the catalytic conversion of renewable resources such as lignocellulose. In order to design sustainable catalytic protocols two key strategies, namely ‘hydrogen borrowing’ and ‘cross-coupling’, have been applied to provide the target high-value products with exceptional selectivity and in-line with the principals of green chemistry. The present work attempts the first steps on a ‘high road’ to profitability from lignin and contributes to the development of fully sustainable and economically viable lignocellulosic biorefineries

Pharmaceutically relevant (hetero)cyclic compounds and natural products from lignin-derived monomers:Present and perspectives

Lignin, the richest source of renewable aromatics on the planet, is an intriguing raw material for the construction of value-added aromatics. In the past decade, much progress has been made regarding the development of efficient lignin depolymerization methods, able to produce specific monophenol derivatives in high-enough selectivity and yields. This now serves as an excellent basis for developing powerful downstream conversion strategies toward a wide range of products, including fine chemical building blocks. The inherent structural features of lignin-derived platform chemicals undoubtedly inspire the development of novel, creative, atom-economic synthetic routes toward biologically active molecules or natural products. In this perspective we attempt to bridge the structural features of lignin-derived platform chemicals with existing synthetic strategies toward the construction of heterocycles and provide a summary of efforts for the production of natural products from aromatics that can be, in principle, obtained from lignin. Last, we comment on the latest efforts that present entire value-chains from wood to valuable pharmaceutically relevant compounds

Amination of beta-hydroxyl acid esters via cooperative catalysis enables access to bio-based beta-amino acid esters

beta-amino acid esters are important scaffolds in medicinal chemistry and valuable building blocks for materials synthesis. Surprisingly, the waste-free construction of such moieties from readily available or renewable starting materials has not yet been addressed. Here we report on a robust and versatile method for obtaining beta-amino acid esters by direct amination of beta-hydroxyl acid esters via the borrowing hydrogen methodology using a cooperative catalytic system that comprises a homogeneous ruthenium catalyst and an appropriate Bronsted acid additive. This method allows for the direct amination of esters of 3-hydroxypropionic acid, a top value-added bio-based platform chemical, opening a simple route to access beta-amino acid esters from a range of renewable polyols including sugars and glycerol

Ruthenium and Iron-Catalysed Decarboxylative N-alkylation of Cyclic α-Amino Acids with Alcohols:Sustainable Routes to Pyrrolidine and Piperidine Derivatives

A modular and waste-free strategy for constructing N-substituted cyclic amines via decarboxylative N-alkylation of α-amino acids employing ruthenium- and iron-based catalysts is presented. The reported method allows the synthesis of a wide range of five- and six-membered N-alkylated heterocycles in moderate-to-excellent yields starting from predominantly proline and a broad range of benzyl alcohols, and primary and secondary aliphatic alcohols. Examples using pipecolic acid for the construction of piperidine derivatives, as well as the one-pot synthesis of α-amino nitriles, are also shown

Synthesis of Enantioenriched Amines by Iron-Catalysed Amination of Alcohols Employing at Least One Achiral Substrate

The synthesis of a broad range of enantioenriched amines by the direct Fe-catalysed coupling of amines with alcohols through the borrowing hydrogen strategy, while at least one of these substrates is achiral is reported. When starting from α-chiral amines and achiral alcohols, a wide range of enantioenriched amine products, including N-heterocyclic moieties can be obtained with complete retention of stereochemistry and the power of this method is demonstrated in the one-step synthesis of known pharmaceuticals from commercially available, simple enantiopure primary amines and achiral alcohols. It was also found that the use of β-branched enantioenriched primary alcohols and achiral amines as reaction partners leads to a partial loss of stereochemical integrity in the final product, however, a systematic optimization enabled partial retention of enantiopurity and possible parameters effecting for racemization were identified.</p

Validation of Molecular Markers of Barley Net Blotch Resistance Loci on Chromosome 3H for Marker-Assisted Selection

The most widespread and harmful disease of barley is net form of net blotch caused by the ascomycete Pyrenophora teres f. teres Drechsler (Ptt). A cost effective and environmentally sustainable strategy for barley protection against Ptt is to develop barley cultivars possessing genetic resistance. In previous GWA analysis, we identified SNP-markers associated with a resistance locus on chromosome 3H in the interval of 45.82-54.53 cM. These SNPs have been described previously in the literature to be located within the same region of chromosome 3H. The aim of the study was to validate QTL markers controlling resistance to Ptt on chromosome 3H in this region by KASP genotyping in four F-2 populations of crosses between the resistant cultivars, Morex, Fox, and Zolo, and the accession, Local k-21578, with the susceptible barley cv. Gesine and in a doubled haploid (DH) population of Canadian Lake Shore (CLS)/Harrington. Eleven of fifteen studied markers showed high efficacy (97.5-100%) for co-segregation with resistance to Ptt in the DH population, CLS/Harrington. Three of these markers located at 54.53 cM and one at 51.27 cM were effective in two F-2 populations of crosses of Morex and Fox with susceptible cv. Gesine. These markers are also located close to each other on the physical map (442,203,921-443,119,491 bp). Apparently, in cultivars, CLS, Morex, and Fox, resistance to Ptt is determined by the same locus. Markers JHI-Hv50k2016-166392 (47.1 cM, 112,536,071 bp), Clone ID 3255462_1 (51.63 cM, 363,531,898 bp), and Clone ID 3255462_2 (51.63 cM, 363,531,871 bp) showed high efficacy in the DH population and in the F-2 population, Local k-21578/Gesine. Apparently, at least two loci controlling Ptt resistance exist in the chromosome region of 47.0-54.3 cM: one at 46.0-48.44 cM and another at 51.27-54.8 cM. These regions were found to harbor several genes involved in important plant functions, including disease response and signaling pathways. Allele-specific PCR markers were developed based on the KASP assay data and tested on six resistant, two moderately resistant, and two susceptible barley genotypes. Four markers were found to be effective to differentiate susceptible and resistant barley genotypes. The KASP and allele-specific PCR markers associated with Ptt resistance on chromosome 3H will be useful for pyramiding resistance QTLs in barley marker-assisted selection

Clean Synthetic Strategies to Biologically Active Molecules from Lignin:A Green Path to Drug Discovery**

Deriving active pharmaceutical agents from renewable resources is crucial to increasing the economic feasibility of modern biorefineries and promises to alleviate critical supply-chain dependencies in pharma manufacturing. Our multidisciplinary approach combines research in lignin-first biorefining, sustainable catalysis, and alternative solvents with bioactivity screening, an in vivo efficacy study, and a structural-similarity search. The resulting sustainable path to novel anti-infective, anti-inflammatory, and anticancer molecules enabled the rapid identification of frontrunners for key therapeutic indications, including an anti-infective against the priority pathogen Streptococcus pneumoniae with efficacy in vivo and promising plasma and metabolic stability. Our catalytic methods provided straightforward access, inspired by the innate structural features of lignin, to synthetically challenging biologically active molecules with the core structure of dopamine, namely, tetrahydroisoquinolines, quinazolinones, 3-arylindoles and the natural product tetrahydropapaveroline. Our diverse array of atom-economic transformations produces only harmless side products and uses benign reaction media, such as tunable deep eutectic solvents for modulating reactivity in challenging cyclization steps.</p

Structural data of phenanthrene-9,10-dicarbonitriles

In this data article, we present the single-crystal XRD data of phenanthrene-9,10-dicarbonitriles. Detailed structure analysis and photophysical properties were discussed in our previous study, "Intermolecular interactions-photophysical properties relationships in phenanthrene-9,10-dicarbonitrile assemblies" (Afanasenko et al., 2020). The data include the intra- and intermolecular bond lengths and angles. (c) 2019 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Intermolecular interactions-photophysical properties relationships in phenanthrene-9,10-dicarbonitrile assemblies

Phenanthrene-9,10-dicarbonitriles show various luminescence behaviour in solution and in the solid state. Aggregation patterns of phenanthrene-9,10-dicarbonitriles govern their luminescent properties in the solid state. Single crystal structures of phenanthrene-9,10-dicarbonitriles showed head-to-tail intraplane (or quasi-intraplane) intermolecular interactions and π-stacking patterns with eclipsing of molecules when viewed orthogonal to the stacking plane. The π-stacking interactions were detected in the X-ray structures of phenanthrene-9,10-dicarbonitriles and studied by DFT calculations at the M06–2X/6–311++G(d,p) level of theory and topological analysis of the electron density distribution within the framework of QTAIM method. The estimated strength of the C⋯C contacts responsible for the π-stacking interactions is 0.6–1.1 kcal/mol. The orientation of molecules in crystals depends on the substituents in phenanthrene-9,10-dicarbonitriles. Distinct molecular orientation and packing arrangements in crystalline phenanthrene-9,10-dicarbonitriles ensured perturbed electronic communication among the nearest and non-nearest molecules through an interplay of excimer and dipole couplings. As a result, the intermolecular interactions govern the solid state luminescence of molecules