One-Flow project deliverables
The page lists 21 deliverables related to the research project "One-Flow".
List of Deliverables
| title and desprition | type | last update |
|---|---|---|
Cascade 3 - b) synthesis of SacubitrilUsing the approach of cascade 3a, the synthesis of sacubitril will be carried out in continuous manner. Programme: H2020-EU.1.2.1. - Topic(s): FETOPEN-01-2016-2017 |
Documents, reports | 2020-04-16 |
Exploiting iterative reactivity of boronic acids via flow generated reactive intermediatesExploitation of a newly discovered iterative carbon-carbon bond forming process developed at UCAM, which involves repeated metal-free coupling of boronic acids (commonly available) with in-situ flow-generated diazo compounds, as reactive intermediates. This process opens up wider opportunities to create functional materials and in particular, novel architectures for the pharmaceutical industry. Programme: H2020-EU.1.2.1. - Topic(s): FETOPEN-01-2016-2017 |
Documents, reports | 2020-04-16 |
Polymersome-based improvement of cascade 1: a) harmonization of catalyst & solventPolymersomes will be used for improving the contact of a biphasic reaction system, as given e.g. between water-soluble enzymes and organic substrates. This results in a strongly enhanced reaction rate, mainly as a result of an improved availability of the enzymes at the biphasic interface. Programme: H2020-EU.1.2.1. - Topic(s): FETOPEN-01-2016-2017 |
Documents, reports | 2020-04-16 |
Cascade 1 - synthesis of cannabinoid derivativesReadily accessible geranyl halides and derivatives thereof will be coupled, using Pd-catalyzed cross-coupling reactions, to olivetolic acid which contains an additional halide substituent at the aromatic ring. Initially, Suzuki or Negishi type coupling reactions will be used in which the geranyl partner is converted into a borinate ester or organozinc compound. Then differently substituted olivetolic acid derivatives will be prepared and coupled to the geranyl derivatives. The final step in the biosynthesis of THC in Cannabis sativa is the ring-closure and subsequent decarboxylation of canna¬bigerolic acid. This unique oxidative cyclization reaction is catalyzed by Δ1-tetrahydrocannabinolic acid synthase (THCAS). The effectiveness of the coupling procedure will be evaluated in close collaboration with ESR Y (WP1) under three conditions: non-compartmentalized, in polymersomes, and in Pickering emulsions Programme: H2020-EU.1.2.1. - Topic(s): FETOPEN-01-2016-2017 |
Documents, reports | 2020-04-16 |
Periodic report action check meeting 2Scientific action check meeting 2 after 28 months Programme: H2020-EU.1.2.1. - Topic(s): FETOPEN-01-2016-2017 |
Documents, reports | 2020-04-16 |
Development of a critical process parameter mapThe processes, developed in WP 1 to 4, will be evaluated towards their critical process parameters. These will be compared to different technology characteristics. This will result in function specifications of the modules, which will specified for a group of processes (cascade/multi-purpose) and a wide range of different conditions. Based on this evaluation at least one demonstration process will be selected for realization and a theoretical realization scenario for a second process. Programme: H2020-EU.1.2.1. - Topic(s): FETOPEN-01-2016-2017 |
Documents, reports | 2020-04-16 |
A new generic microcontroller remote command and control device for chemical reactions in flowThe control platform [the Blueberry Muffin (BBM)] will be able to seamlessly manage equipment modules from different vendors and go beyond simple machine to machine communi¬cation (M2M) to a new level whereby the machines evolve and adapt to a changing environment. Advanced innovative software, neural networking of chemical devices and machine learning techniques will be interconnected and networked through a “Chemical Internet of Chemical Thingsâ€. Programme: H2020-EU.1.2.1. - Topic(s): FETOPEN-01-2016-2017 |
Documents, reports | 2020-04-16 |
Application of the systemic operation factory in cascade 4Using the systemic operations factory approach and the data obtained in Task 3.1., cascade 4 will be optimized. A computer-aided method based on the data bases and on the criteria will help to minimize the number of unit operations as well as the operating conditions for a particular target molecule in order to approach “One-Flow†operation. Just to give an example, matrixes may be built to check for orthogonality, the latter being assessed as a binary answer 0 or 1. The criteria for chemical orthogonality will be defined as 0 when, in a two reactions system, the yields of the expected products are > 99% and without degradation of the yield in solution for a time long enough to proceed with further workup. In any other situation, a non-orthogonal notation (1) is given. Minimizing the value of the matrixes will drive to (close to) One-Flow operations. Programme: H2020-EU.1.2.1. - Topic(s): FETOPEN-01-2016-2017 |
Documents, reports | 2020-04-16 |
Data acquisitionFor all cascades under investigation, data acquisition will be perfor¬med from solubility, miscibility, vapor pressure and equipment data bases. Most of these data are available in the open literature and will be collected and used. Part of the equipment data base will be available from the French project PROCIP (2010-2014) funded by the French National Agency for Research (ANR). Other equipment more specific to Flow Chemistry are not yet included in the PROCIP equipment data base and should be worked out (Syrris type, etc…). Other data such as the reaction time and the chemical orthogonality might require inputs from WP1 and some experimental work with flow technics available at CNRS. All available data bases (solvent miscibility, …) will also be collected but other will be created for the purpose of the project. Programme: H2020-EU.1.2.1. - Topic(s): FETOPEN-01-2016-2017 |
Documents, reports | 2020-04-16 |
Shifting the epimerization equilibrium of cascade 2Shifting the epimerization equilibrium of cascade 2 Programme: H2020-EU.1.2.1. - Topic(s): FETOPEN-01-2016-2017 |
Documents, reports | 2020-04-16 |
Spaciant-based solvent dispersion and unification for cascade 4Smart solvents, such as supercritical CO2, ionic liquids and fluorous solvents (where needed thermomorphic solvents), will be used to allow the operation of two orthogonal catalysts in close proximity (i.e., in one reactor), which however cannot be dissolved in the same solvent. After reaction, by external stimulus such as cooling down or releasing CO2 gas, the catalysts and their respective solvents will be separated. For Cascade 4, a chemo and biocatalyst will be treated this way. The solvents need to be selected in such way, that reactants and products also will remain in different phases. Then, there is no need for product and catalyst separation, but is rather “automatically†achieved. The investigations follow a generic aim beyond the catalysts and reactants of Cascade 4.There is a multitude of spaciants combination possible for a multitude of processing and purification tasks; some of these will be tested. TUE has complete overview over all relevant literature and made two reviews about, see the following non-published table (shown first time here). Programme: H2020-EU.1.2.1. - Topic(s): FETOPEN-01-2016-2017 |
Documents, reports | 2020-04-16 |
Application of the microcontroller in cascade 1An optimization of the cascades will be performed under the constraints of systemic interaction. Computer-aided optimization (see BBM approach) or DoE-experimentation seems to be adequate means to address complexity of this task. Programme: H2020-EU.1.2.1. - Topic(s): FETOPEN-01-2016-2017 |
Documents, reports | 2020-04-16 |
Criteria definition and orthogonality decision executionCriteria defining compatibility are also required. For example, catalyst deactivation per se might kill several options for equipment in flow mode. The chemical functionalities of those cas¬cades will be checked for their orthogonality and proposals will be made for replacement based on an inventory made collecting known orthogonal functionalities. Programme: H2020-EU.1.2.1. - Topic(s): FETOPEN-01-2016-2017 |
Documents, reports | 2020-04-16 |
Catalyst slurries in multi-phase micro-flowsMulti-phase micro-flow processing recirculating heterogeneous catalyst slurries will be developed for the first and/or third chemical step in cascade 4. It needs to be exerted in the presence of enzymes which constitutes entirely new kind of processing. Even the normal use of such kind of processing is scarcely reported and CNRS have a leading position here. For example, three-phase gas-liquid-liquid segmented flow has been reported for material synthesis, crystallization, or enhanced LL mixing, yet only two papers deal with reaction. In turn, that has been approached by CNRS and they demonstrated quantitatively the viability and the robustness of a GLS system under reactive conditions and performed several basic engineering studies on hydrodynamic and LS mass transport. Programme: H2020-EU.1.2.1. - Topic(s): FETOPEN-01-2016-2017 |
Documents, reports | 2020-04-16 |
Cascade 4 - Synthesis of CapecitabineAt first the individual reaction steps will be studied and suitable catalysts will be identified by means of a screening of organo- and biocatalysts, respectively. Subsequently, process development for the desired key steps for the multi-step synthesis of the Capecitabine key intermediate will be done, followed by an experimental and theoretical study rationalizing the compatibility of the organocatalytic with the enzymatic reactions. Finally, the combination of the steps in a batch-process will be carried out to serve as the benchmark for the subsequent combination under flow. Programme: H2020-EU.1.2.1. - Topic(s): FETOPEN-01-2016-2017 |
Documents, reports | 2020-04-16 |
Enable a co-catalyst flow operation for cascade 3A combined Pickering-anchoring strategy will be developed to allow a co-flow operation of both catalysts in one fixed-bed reactor, i.e. once the C-C coupling product is formed, it is hydrolyzed immediately at its ester function. For this, a Pickering emulsion containing one catalyst in combination with an immobilization of the chemocatalyst to a solid support will be used. The enzyme hydrolase will be either placed within an emulsifier particle or be the stabilizing particle itself, while the Pd catalyst will be chemically anchored to a solid support, such as functionalized silica particles or monoliths using bis(oxazoline) as organic linkers that strongly bind palladium. Such hybrid operation is thought to be superior to a monolithic use of Pickering emulsions and anchored catalysts alone, allowing (i) higher through¬put (lower pressure drop), (ii) operational simplicity (KISS-based process design), (iii) better reaction outcome. Detailed surface analysis of the catalyst/Pickering emulsion particles and reactor walls will be done before and after reaction and ICP/MS measurements of Pd in the solvents and products will be carried out. Programme: H2020-EU.1.2.1. - Topic(s): FETOPEN-01-2016-2017 |
Documents, reports | 2020-04-16 |
Cascade 2 - synthesis of ursodeoxycholic acidThe first step of this task comprises a highly selective dihydroxylation at the 12-position of naturally available cholic acid. In nature so-called dehydroxylases were identified that can carry out this transformation. This enzyme will be identified, expressed and characterized. In the second step, an isomerization will be carried out. 7a and 7b-Hydroxysteroid-dehydroge¬nases as immobilized cell-free enzymes carry out this step with high yields and selectivities. Co-immobilisation of these enzymes will be carried out in Pickering emulsions, possibly in combination with cross-linking. In the final stage of the cascade, compatibility of the two steps will be studied, taking into account the Programme: H2020-EU.1.2.1. - Topic(s): FETOPEN-01-2016-2017 |
Documents, reports | 2020-04-16 |
Cascade 3 – a) synthesis of ValsartanValsartan is synthesized continuously in a fixed bed reactor with three different segments. The first step is catalyzed by a base, e.g. K2CO3, which is also needed for the Suzuki-Miyaura coupling and thus can be used for both reactions. For the latter self-made heteroge¬neous Pd-catalysts will be used. These catalysts are either Ce-Sn-Pd (CexSn1-xPd0.01O2-δ) catalysts or Pd-immobilized via a bis(oxazoline) ligand on functionalized silica-gel particles or monoliths. Preliminary experiments will show if it is necessary to protect the tetrazole ring at the free amine position. The last step of the synthesis involves the conversion of the methylester to the acid using an immobilized hydrolase. Programme: H2020-EU.1.2.1. - Topic(s): FETOPEN-01-2016-2017 |
Documents, reports | 2020-01-20 |
Technical action check meeting 1Scientific action check meeting 1 after 16 months Programme: H2020-EU.1.2.1. - Topic(s): FETOPEN-01-2016-2017 |
Documents, reports | 2020-01-20 |
Data Management PlanData Management will be provided and updated during the execution of the project Programme: H2020-EU.1.2.1. - Topic(s): FETOPEN-01-2016-2017 |
Open Research Data Pilot | 2020-01-20 |
Project webpage and logoTask PMD 1. Creation of a project webpage and a logo (TUE-1, M1-2) Webpage and project logo. Programme: H2020-EU.1.2.1. - Topic(s): FETOPEN-01-2016-2017 |
Websites, patent fillings, videos etc. | 2020-01-20 |