Lignin as a sustainable feedstock: Upgrading of lignin to chiral synthons
Lead Research Organisation:
University College London
Department Name: Chemistry
Abstract
To ensure that we have a sustainable chemical industry, not reliant on petrochemical feedstocks, it is essential that alternative renewable starting materials are used for the production of fine chemicals and pharmaceuticals. The richest source of aromatic compounds is lignin, a highly oxygenated polymer. However, the efficient conversion of lignin into aromatic synthons is still a major challenge. To enable the utilisation of lignin, new methods are needed for its depolymerisation and/or selective modifications, whilst using existing chiral functional groups. This project will develop new routes for the selective modification of lignin, to provide access to valuable chiral compounds via sustainable chemistries. Recent reports have described the aerial oxidation of lignin to e.g Ligninox and depolymerisation to mainly benzoates or deoxygenated compounds (Sch. 1).1,2 However these methods suffer from the use of forcing reaction conditions, toxic reagents and the loss of useful functionalities. In recent work we have identified a method for the selective cyclisation of pentose hydrazones via loss of the C-2 hydroxyl group under acidic or basic conditions and then cyclisation. Here we will apply this approach to the fragmentation and functionalization of lignin and lignin fragments. This strategy has the potential to assist in the selective fragmentation of lignin, while retaining functional groups for further modification using chemical or enzymatic steps.
Proposed research: Initial work will focus on the use of the beta-O-4 and Ligninox model compounds to establish application of the hydrazone methodology to cleave the O-aryl ether bond, and introduce either a hydroxyl group or another nucleophile (Nuc) (Sch. 2). For the beta-O-4 model lignin initial oxidation will be carried out using alcohol dehydrogenase (ADH) libraries available (some coexpressed with the NADH recycling co-factor) or a chemical oxidation method, with subsequent hydrazone formation and cleavage. Compounds obtained, both the phenolics and hydrazones, will be separated using resins for further synthetic manipulations. These include hydrazone hydrolysis (Amberlyst) and reaction with available norcoclaurine synthases (NCSs), transaminases (TAms), and transketolases (TKs) to give single isomer products.4 Similarly, with Ligninox, hydrazone formation, ether cleavage and addition of Nuc, hydrolysis to the ketone and reaction with e.g. TAms will give chiral amines: products accessible from these synthons include amides and cyclic amines, epoxides and aziridines. These are representative conversions: notably only the bioconversion of lignin-derived
vanillin to the corresponding achiral amine using TAms has been reported highlighting the significant potential of biomass-chemistry-biocatalysis strategies to access medicinally relevant compounds. Biocatalytic systems can uniquely give single isomer chiral compounds with exquisite stereocontrol.
Proposed research: Initial work will focus on the use of the beta-O-4 and Ligninox model compounds to establish application of the hydrazone methodology to cleave the O-aryl ether bond, and introduce either a hydroxyl group or another nucleophile (Nuc) (Sch. 2). For the beta-O-4 model lignin initial oxidation will be carried out using alcohol dehydrogenase (ADH) libraries available (some coexpressed with the NADH recycling co-factor) or a chemical oxidation method, with subsequent hydrazone formation and cleavage. Compounds obtained, both the phenolics and hydrazones, will be separated using resins for further synthetic manipulations. These include hydrazone hydrolysis (Amberlyst) and reaction with available norcoclaurine synthases (NCSs), transaminases (TAms), and transketolases (TKs) to give single isomer products.4 Similarly, with Ligninox, hydrazone formation, ether cleavage and addition of Nuc, hydrolysis to the ketone and reaction with e.g. TAms will give chiral amines: products accessible from these synthons include amides and cyclic amines, epoxides and aziridines. These are representative conversions: notably only the bioconversion of lignin-derived
vanillin to the corresponding achiral amine using TAms has been reported highlighting the significant potential of biomass-chemistry-biocatalysis strategies to access medicinally relevant compounds. Biocatalytic systems can uniquely give single isomer chiral compounds with exquisite stereocontrol.
Organisations
People |
ORCID iD |
Helen Hailes (Primary Supervisor) | |
Eve Carter (Student) |
Publications
Roddan R
(2022)
Chemoenzymatic approaches to plant natural product inspired compounds.
in Natural product reports
Carter EM
(2021)
Direct Conversion of Hydrazones to Amines using Transaminases.
in ChemCatChem
Wang Y
(2022)
Enzymatic synthesis of benzylisoquinoline alkaloids using a parallel cascade strategy and tyrosinase variants
in Nature Communications
Jockmann E
(2023)
Expanding the Substrate Scope of N - and O -Methyltransferases from Plants for Chemoselective Alkylation**
in ChemCatChem
Ambrose-Dempster E
(2023)
Mechanoenzymatic reactions for the hydrolysis of PET.
in RSC advances
Carter E
(2022)
Mechanoenzymatic reactions with whole cell transaminases: shaken, not stirred
in Green Chemistry
Cárdenas-Fernández M
(2023)
The Discovery of Imine Reductases and their Utilisation for the Synthesis of Tetrahydroisoquinolines.
in ChemCatChem
Description | Work has been published investigating the novel reaction of hydrazones with transaminase enzymes in ChemCatChem (DOI: 10.1002/cctc.202101008). This work details how hydrazones can be hydrolysed to form aldehydes in situ which then react with transaminases to form amines. Work has also been published on the reaction of transaminases under mechanoenzymatic conditions in Green Chemistry (DOI: 10.1039/D2GC01006B). This describes how transaminases can be used in a ball mill with little solvent to form amines from aldehydes. High yields and selectivities were observed. The reaction of tyrosinases in a ball mill is still being investigated in the Hailes group as a method to break down lignin. Eve Carter has also made contributions to other publications involving chemoenzymatic approaches to plant natural product inspired compounds (DOI: 10.1039/D2NP00008C), novel imine reductases (DOI: 10.1002/cctc.202201126) and the synthesis of benzylisoquinoline alkaloids using tyrosinases (DOI: 10.1038/s41467-022-33122-1). She has now passed her PhD viva and her thesis will be available online through UCL. |
Exploitation Route | In order for research on the mechanoenzymatic results of lignin to be publishable, ideally the reaction products would be identified and yields calculated. |
Sectors | Agriculture, Food and Drink,Chemicals,Environment,Pharmaceuticals and Medical Biotechnology |
Description | Oral presentation at a conference in Rome 2022 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | I presented my mechanoenzymatic research as an oral presentation at The First Symposium for Young Chemists: Innovation and Sustainability in Rome, June 2022. There were interesting questions and discussions afterwards. |
Year(s) Of Engagement Activity | 2022 |
Description | Poster presentation at Biotrans 2021 Graz |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | I presented a poster at Biotrans 2021, which was held online. Undergraduates, postgraduates, academics and industrial chemists all joined and were able to view my poster and ask me questions. I discussed my research with a few academics and postgraduates who had interesting questions and suggestions of things for me to try. |
Year(s) Of Engagement Activity | 2021 |
Description | Poster presentation for BMCS |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | I presented a poster at the Biological and Medicinal Chemistry Symposium for Postgraduates 2021, which was held online. Postgraduates joined and were able to view my poster and ask me questions. I discussed my research with a few people who had interesting questions and suggestions of things for me to try. |
Year(s) Of Engagement Activity | 2021 |
Description | Presentation in ISMB Friday wrap |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | I presented my research at the Institute of Structural and Molecular Biology 'Friday Wrap', which was held online. Members of relevant departments at UCL and Birkbeck were able to listen to my presentation and ask me questions about my research. |
Year(s) Of Engagement Activity | 2021 |
Description | Presented a poster at the RSC chemical biology symposium |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | I presented a poster at the RSC Chemical Biology symposium 2021, which was held online. Undergraduates, postgraduates, academics and industrial chemists all joined and were able to view my poster and ask me questions. I discussed my research with a few academics and postgraduates who had interesting questions. |
Year(s) Of Engagement Activity | 2021 |
Description | Presented a poster for organic division poster symposium |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Postgraduate students |
Results and Impact | I presented a poster at the RSC Organic Division poster symposium 2021, which was held online. Postgraduates and academics joined and were able to view my poster and ask me questions. I discussed my research with a few academics and postgraduates who had interesting questions and suggestions of things for me to try. |
Year(s) Of Engagement Activity | 2021 |
Description | Presented my research at the UCL 'Chemical Sustainability Research Theme seminar' |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | I presented my research at a departmental seminar known as the 'Chemical Sustainability Research Theme seminar', which was held online. Members of the Chemistry Department and other departments at UCL were able to listen to my presentation and ask me questions about my research. |
Year(s) Of Engagement Activity | 2021 |
Description | Second year poster presentation |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | All second year PhD students at UCL Chemistry Department are required to do a poster presentation about their research. This year, due to the coronavirus pandemic, this event was held online rather than in person. Staff and postgraduates were able to join the session, viewing my poster and discussing my work with me. I won an award for the best poster for the Organic Section. |
Year(s) Of Engagement Activity | 2020 |