The aim of this project is to bring together subject matter experts from the academic and non-academic sectors to develop and exemplify the use of new catalysts and new green reactions to manufacture important halogenated compounds that could be used in drug discovery and drug production. In order to achieve this objective the proposal brings together 3 partners with complementary skills: University of Naples (UNINA): expertise in medicinal chemistry and drug discovery. KelAda Pharmachem: expertise in green chemistry, chemical batch process development and scale-up. UCO: expertise in process engineering of continuous flow processes. We have broken this proposal into the following separate technical Work Packages: WP1: Preparation of new catalysts for efficient desymmetrization [WP Leader: UNINA]. WP2: Development of enantiospecific halogenation including Fluorination. [WP Leader: Kelada Pharmachem]. WP3 Drug Candidate, library creation & in vitro testing. [WP Leader: Kelada Pharmachem] WP4 Development of flow variant and scale-up.[WP Leader: UCO} The above WP's will be undertaken via a series of interlinked secondment of researchers between the consortium partners and will be complemented by a series of training and other initiatives to facilitate interdisciplinary and inter-sectoral knowledge sharing and exchange.

The aim of this project is to bring together subject matter experts from the academic and non-academic sectors to develop a platform of “green” chemoenzymatic methods for the production of high value active pharmaceutical ingredients – both those currently on the market, and those in development pipelines of the Pharma industry. The partners will exemplify the use of the platform through its application in the production of 4 drugs currently on the market – namely Duloxetine, Atomexetine, Ramosetron and Paricalcitol. In order to achieve this objective the proposal brings together 3 partners with complementary skills: Kelada Pharmachem: Phase transfer catalysis/organo catalysis/scale-up of chemical processes Cerbios Pharma: Biocatalysis and fermentation methodologies for drug production IC-CNR: Protein crystallography and enzymatic engineering

TransPharm two-track approach focusses on the one hand on the compounds itself by identifying greener and more sustainable-by-design Active Pharmaceutical Ingredients (APIs) and on the other hand reducing the environmental impact and resilience of the manufacturing process by optimizing the synthesis route of new APIs in continuous flow and by proposing greener alternative solvents. The aim of the project is to (i) analyse and predict flow behaviour and environmental biodegradability of APIs and their synthesis pathways; (ii) identify greener and more sustainable alternatives to pharmaceutical products / APIs of concern; (iii) reduce the footprint and create important shortcuts in synthetic schemes of APIs; and (iv) assess the sustainability of pharmaceuticals over their entire life cycle. To reach the envisaged aims, the project will deliver four toolboxes (consisting of digital tools and guidelines) for the development of greener pharmaceutical products and APIs. These toolboxes will be used to (v) assess the potential to move towards the transition to greener, more agile pharmaceutical production. In addition, TransPharm will elaborate on the business case for sustainable pharmaceutical products or APIs and what is needed to bring them to the market. The project will also make sure that (vi) key project results and knowledge are properly transferred towards targeted stakeholders. TransPharm?s outcome contribute to a Europe, that is self-sufficient by reducing dependence on API production in third countries; making the EU healthcare industry more competitive, sustainable and reliable, ensuring timely supply of essential medicines from particularly complex or critical supply and distribution chains and positioning EU as a leader in innovative technologies.

Global terrestrial plant biodiversity remains a largely untapped source of natural bioactive compounds. In fact, valid sources are even “hiding in plain sight”, yet not “within reach” due to lack of effective technical solutions to unlock their potential. In this context, the PROSPLIGN consortium has developed an innovative bioprospecting approach that uses cutting-edge and complementary chemical and enzymatic methods, supported by statistical analysis and coupled with high-throughput detection methods, to enable the discovery of bioactive molecules from lignin, one of the fractions of the most abundant biopolymer on Earth (lignocellulose). Lignin “chemical biodiversity” will enable PROSPLIGN to cover three target markets (pharmaceuticals, cosmetics and fragrances) with a combined market of >€1.4 trillion. The project will use lignin derived from 9 different species and investigate at least 3 different chemical approaches and 10 different enzymes to obtain up to 1000 mixtures of lignin-derived compounds, and then pass a progressively narrower “hit validation funnel” in industrially relevant environments, being screened via up to 17 different bioactivity assays. Sustainable production routes for at least 2 of the most promising compounds per sector, directly or following derivatisation, will be proposed. Compared to traditional approaches, PROSPLIGN's bioprospecting avoids animal cruelty, expensive exploration efforts (no novel animal/plants discovery), disruptive extractions (seeking “hidden gems” in an abundant but underexploited “biomass mine”), and directly targets the liberation of readily testable bio/chemical-functionality present in plant material, superior to other approaches relying on “manipulation-intensive” microbial strain culture or “extrapolation” from DNA/RNA). Ultimately, PROSPLIGN will contribute to a new generation of biobased bioactives, unlocking more value from existing sources whose immense potential has yet to be harnessed.

The aim of this project is to bring together subject matter experts from the academic and non-academic sectors to develop three new categories of quaternary ammonium salts to be used as catalysts for the cost-efficient and green manufacture of high value active pharmaceutical ingredients. In order to achieve this objective the proposal brings together 3 partners with complementary skills: University of Naples(UNIN): experts in the preparation and purification of cyclic peptides. Experts in solid phase synthesis and immobilisation of peptides on solid support. KelAda Pharmachem: Phase transfer catalysis/organo catalysis/scale-up of chemical processes University of Linz(JKU Linz): experts in design of new ammonium salts and optimisation of enantioselective phase transfer catalyses. We have broken this proposal into the following separate Work Packages: WP1. Preparation of new designer ammonium salts [WP leader: Kelada] WP2. Preparation of cyclic peptide based ammonium salts [WP leader: UNINA] WP3. Evaluation of new ammonium salt catalysts prepared through WP1 [WP JKULinz] WP4. Evaluation of new Ammonium salt catalysts prepared through WP2[WP leader: UNINA] WP5. Application of Ammonium salts to drug production [WP leader: Kelada] WP6. Scale up of key steps or the manufacture of drugs [WP leader: Kelada] WP 7. Management, Communication & Dissemination [WP leader: KelAda] The above WP’s will be undertaken via a series of interlinked secondment of researchers between consortium partners and will be complemented by a series of training and other initiatives to facilitate interdisciplinary and intersectoral knowledge sharing and exchange.