Project acronym ANaPSyS
Project Artificial Natural Products System Synthesis
Researcher (PI) Tanja Gaich
Host Institution (HI) UNIVERSITAT KONSTANZ
Call Details Starting Grant (StG), PE5, ERC-2015-STG
Summary "Traditionally, natural products are classified into ""natural product families"". Within a family all congeners display specific structure elements, owing to their common biosynthetic pathway. This suggests a bio-inspired or ""collective synthesis"", as has been devised by D: W. MacMillan. However, a biosynthetic pathway is confined to these structure elements, thus limiting synthesis with regard to structure diversification. In this research proposal the applicant exemplarily devises a strategic concept to overcome these limitations, by replacing the dogma of ""retrosynthetic analysis"" with ""structure pattern recognition"". This concept is termed ""Artificial Natural Product Systems Synthesis — ANaPSyS"", and aims to supersede the current ""logic of chemical synthesis"" as a standard practice in this field.
ANaPSyS exclusively categorizes natural products based on structural relationships — regardless of biogenetic origin. The structure pattern analysis groups natural products according to their shared core structure, and thereof creates a common precursor called ""privileged intermediate (PI)"". This intermediate is resembled in each of these natural products and is architecturally less complex. As a result every member of this natural product group can originate from a different natural product family and is obtained via this ""privileged intermediate"", which serves as basis for the artificial synthetic network.
With ANaPSyS a synthetic route is not restricted to a single target structure anymore (as in conventional synthesis). In comparison with bio-inspired synthesis, which is limited to a single natural product family, ANaPSyS enables the synthesis of a whole set of natural product families. With every synthesis accomplished, the network is upgraded — hence diversification leads to a rise in revenue. As a consequence, synthetic efficiency is drastically enhanced, therefore profoundly boosting and facilitating lead structure development.
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Summary
"Traditionally, natural products are classified into ""natural product families"". Within a family all congeners display specific structure elements, owing to their common biosynthetic pathway. This suggests a bio-inspired or ""collective synthesis"", as has been devised by D: W. MacMillan. However, a biosynthetic pathway is confined to these structure elements, thus limiting synthesis with regard to structure diversification. In this research proposal the applicant exemplarily devises a strategic concept to overcome these limitations, by replacing the dogma of ""retrosynthetic analysis"" with ""structure pattern recognition"". This concept is termed ""Artificial Natural Product Systems Synthesis — ANaPSyS"", and aims to supersede the current ""logic of chemical synthesis"" as a standard practice in this field.
ANaPSyS exclusively categorizes natural products based on structural relationships — regardless of biogenetic origin. The structure pattern analysis groups natural products according to their shared core structure, and thereof creates a common precursor called ""privileged intermediate (PI)"". This intermediate is resembled in each of these natural products and is architecturally less complex. As a result every member of this natural product group can originate from a different natural product family and is obtained via this ""privileged intermediate"", which serves as basis for the artificial synthetic network.
With ANaPSyS a synthetic route is not restricted to a single target structure anymore (as in conventional synthesis). In comparison with bio-inspired synthesis, which is limited to a single natural product family, ANaPSyS enables the synthesis of a whole set of natural product families. With every synthesis accomplished, the network is upgraded — hence diversification leads to a rise in revenue. As a consequence, synthetic efficiency is drastically enhanced, therefore profoundly boosting and facilitating lead structure development.
"
Max ERC Funding
1 497 000 €
Duration
Start date: 2016-04-01, End date: 2021-03-31
Project acronym BEGMAT
Project Layered functional materials - beyond 'graphene'
Researcher (PI) Michael Janus Bojdys
Host Institution (HI) HUMBOLDT-UNIVERSITAET ZU BERLIN
Call Details Starting Grant (StG), PE5, ERC-2015-STG
Summary There is an apparent lack of non-metallic 2D-matrials for the construction of electronic devices, as only five materials of the “graphene family” are known: graphene, hBN, BCN, fluorographene, and graphene oxide – none of them with a narrow bandgap close to commercially used silicon. This ERC-StG proposal, BEGMAT, outlines a strategy for design, synthesis, and application of layered, functional materials that will go beyond this exclusive club. These materials “beyond graphene” (BEG) will have to meet – like graphene – the following criteria:
(1) The BEG-materials will feature a transfer of crystalline order from the molecular (pm-range) to the macroscopic level (cm-range),
(2) individual, free-standing layers of BEG-materials can be addressed by mechanical or chemical exfoliation, and
(3) assemblies of different BEG-materials will be stacked as van der Waals heterostructures with unique properties.
In contrast to the existing “graphene family”,
(4) BEG-materials will be constructed in a controlled way by covalent organic chemistry in a bottom-up approach from abundant precursors free of metals and critical raw materials (CRMs).
Moreover – and unlike – many covalent organic frameworks (COFs),
(5) BEG-materials will be fully aromatic, donor-acceptor systems to ensure that electronic properties can be addressed on macroscopic scale.
The potential to make 2D materials “beyond graphene” is a great challenge to chemical bond formation and material design. In 2014 the applicant has demonstrated the feasibility of the concept to expand the “graphene family” with triazine-based graphitic carbon, a compound highlighted as an “emerging competitor for the miracle material” graphene. Now, the PI has the opportunity to build a full-scale research program on layered functional materials that offers unique insights into controlled, covalent linking-chemistry, and that addresses practicalities in device manufacture, and structure-properties relationships.
Summary
There is an apparent lack of non-metallic 2D-matrials for the construction of electronic devices, as only five materials of the “graphene family” are known: graphene, hBN, BCN, fluorographene, and graphene oxide – none of them with a narrow bandgap close to commercially used silicon. This ERC-StG proposal, BEGMAT, outlines a strategy for design, synthesis, and application of layered, functional materials that will go beyond this exclusive club. These materials “beyond graphene” (BEG) will have to meet – like graphene – the following criteria:
(1) The BEG-materials will feature a transfer of crystalline order from the molecular (pm-range) to the macroscopic level (cm-range),
(2) individual, free-standing layers of BEG-materials can be addressed by mechanical or chemical exfoliation, and
(3) assemblies of different BEG-materials will be stacked as van der Waals heterostructures with unique properties.
In contrast to the existing “graphene family”,
(4) BEG-materials will be constructed in a controlled way by covalent organic chemistry in a bottom-up approach from abundant precursors free of metals and critical raw materials (CRMs).
Moreover – and unlike – many covalent organic frameworks (COFs),
(5) BEG-materials will be fully aromatic, donor-acceptor systems to ensure that electronic properties can be addressed on macroscopic scale.
The potential to make 2D materials “beyond graphene” is a great challenge to chemical bond formation and material design. In 2014 the applicant has demonstrated the feasibility of the concept to expand the “graphene family” with triazine-based graphitic carbon, a compound highlighted as an “emerging competitor for the miracle material” graphene. Now, the PI has the opportunity to build a full-scale research program on layered functional materials that offers unique insights into controlled, covalent linking-chemistry, and that addresses practicalities in device manufacture, and structure-properties relationships.
Max ERC Funding
1 362 538 €
Duration
Start date: 2016-08-01, End date: 2021-07-31
Project acronym CatASus
Project Cleave and couple: Fully sustainable catalytic conversion of renewable resources to amines
Researcher (PI) Katalin Barta Weissert
Host Institution (HI) RIJKSUNIVERSITEIT GRONINGEN
Call Details Starting Grant (StG), PE5, ERC-2015-STG
Summary Amines are crucially important classes of chemicals, widely present in pharmaceuticals, agrochemicals and surfactants. Yet, surprisingly, a systematic approach to obtaining this essential class of compounds from renewables has not been realized to date.
The aim of this proposal is to enable chemical pathways for the production of amines through alcohols from renewable resources, preferably lignocellulose waste. Two key scientific challenges will be addressed: The development of efficient cleavage reactions of complex renewable resources by novel heterogeneous catalysts; and finding new homogeneous catalyst based on earth-abundant metals for the atom-economic coupling of the derived alcohol building blocks directly with ammonia as well as possible further functionalization reactions. The program is divided into 3 interrelated but not mutually dependent work packages, each research addressing a key challenge in their respective fields, these are:
WP1: Lignin conversion to aromatics; WP2: Cellulose-derived platform chemicals to aromatic and aliphatic diols and solvents. WP3: New iron-based homogeneous catalysts for the direct, atom-economic C-O to C-N transformations.
The approach taken will embrace the inherent complexity present in the renewable feedstock. A unique balance between cleavage and coupling pathways will allow to access chemical diversity in products that is necessary to achieve economic competitiveness with current fossil fuel-based pathways and will permit rapid conversion to higher value products such as functionalized amines that can enter the chemical supply chain at a much later stage than bulk chemicals derived from petroleum. The proposed high risk-high gain research will push the frontiers of sustainable and green chemistry and reach well beyond state of the art in this area. This universal, flexible and iterative approach is anticipated to give rise to a variety of similar systems targeting diverse product outcomes starting from renewables.
Summary
Amines are crucially important classes of chemicals, widely present in pharmaceuticals, agrochemicals and surfactants. Yet, surprisingly, a systematic approach to obtaining this essential class of compounds from renewables has not been realized to date.
The aim of this proposal is to enable chemical pathways for the production of amines through alcohols from renewable resources, preferably lignocellulose waste. Two key scientific challenges will be addressed: The development of efficient cleavage reactions of complex renewable resources by novel heterogeneous catalysts; and finding new homogeneous catalyst based on earth-abundant metals for the atom-economic coupling of the derived alcohol building blocks directly with ammonia as well as possible further functionalization reactions. The program is divided into 3 interrelated but not mutually dependent work packages, each research addressing a key challenge in their respective fields, these are:
WP1: Lignin conversion to aromatics; WP2: Cellulose-derived platform chemicals to aromatic and aliphatic diols and solvents. WP3: New iron-based homogeneous catalysts for the direct, atom-economic C-O to C-N transformations.
The approach taken will embrace the inherent complexity present in the renewable feedstock. A unique balance between cleavage and coupling pathways will allow to access chemical diversity in products that is necessary to achieve economic competitiveness with current fossil fuel-based pathways and will permit rapid conversion to higher value products such as functionalized amines that can enter the chemical supply chain at a much later stage than bulk chemicals derived from petroleum. The proposed high risk-high gain research will push the frontiers of sustainable and green chemistry and reach well beyond state of the art in this area. This universal, flexible and iterative approach is anticipated to give rise to a variety of similar systems targeting diverse product outcomes starting from renewables.
Max ERC Funding
1 500 000 €
Duration
Start date: 2016-05-01, End date: 2021-04-30
Project acronym PEP-PRO-RNA
Project Peptide-derived bioavailable macrocycles as inhibitors of protein-RNA and protein-protein interactions
Researcher (PI) Tom Grossmann
Host Institution (HI) STICHTING VU
Call Details Starting Grant (StG), PE5, ERC-2015-STG
Summary The objective of this proposal is the elucidation of general principles for the design of bioavailable peptide-derived macrocyclic compounds and their use for the development of inhibitors of protein‒protein (PPI) and protein‒RNA interactions (PRI). Over the last decade, drug discovery faced the problem of decreasing success rates which is mainly caused by the fact that numerous novel biological targets are reluctant to classic small molecule modulation. In particular, that holds true for PPIs and PRIs. Approaches that allow the modulation of these interactions provide access to therapeutic agents targeting crucial biological processes that have been considered undruggable so far. Herein, I propose the use of irregularly structured peptide binding epitopes as starting point for the design of bioactive macrocycles. In a two-step process high target affinity and bioavailability are installed:
1) Peptide macrocyclization for the stabilization of the irregular bioactive secondary structure
2) Evolution of the cyclic peptide into a bioavailable macrocyclic compound
Using a well-characterized model system developed in my lab, initial design principles will be elucidated. These principles are subsequently used and refined for the development of macrocyclic PPI and PRI inhibitors. The protein‒protein and protein‒RNA complexes selected as targets are of therapeutic interest and corresponding inhibitors hold the potential to be pursued in subsequent drug discovery campaigns.
Summary
The objective of this proposal is the elucidation of general principles for the design of bioavailable peptide-derived macrocyclic compounds and their use for the development of inhibitors of protein‒protein (PPI) and protein‒RNA interactions (PRI). Over the last decade, drug discovery faced the problem of decreasing success rates which is mainly caused by the fact that numerous novel biological targets are reluctant to classic small molecule modulation. In particular, that holds true for PPIs and PRIs. Approaches that allow the modulation of these interactions provide access to therapeutic agents targeting crucial biological processes that have been considered undruggable so far. Herein, I propose the use of irregularly structured peptide binding epitopes as starting point for the design of bioactive macrocycles. In a two-step process high target affinity and bioavailability are installed:
1) Peptide macrocyclization for the stabilization of the irregular bioactive secondary structure
2) Evolution of the cyclic peptide into a bioavailable macrocyclic compound
Using a well-characterized model system developed in my lab, initial design principles will be elucidated. These principles are subsequently used and refined for the development of macrocyclic PPI and PRI inhibitors. The protein‒protein and protein‒RNA complexes selected as targets are of therapeutic interest and corresponding inhibitors hold the potential to be pursued in subsequent drug discovery campaigns.
Max ERC Funding
1 499 269 €
Duration
Start date: 2016-03-01, End date: 2021-02-28
Project acronym TimePROSAMAT
Project Time-Programmed Self-Assemblies and Dynamic Materials
Researcher (PI) Andreas Jean Leopold Walther
Host Institution (HI) ALBERT-LUDWIGS-UNIVERSITAET FREIBURG
Call Details Starting Grant (StG), PE5, ERC-2015-STG
Summary "TimeProSAMAT aims to introduce concepts to program the time domain of self-assembled systems and materials in CLOSED systems under non-equilibrium conditions by controlling the kinetics of assembly and disassembly pathways via (i) modulating the surrounding by feedback systems, (ii) dissipative structure formation and (iii) active structural feedback. After reaching a fundamental understanding on a SA level, we want to capitalize on these enabling SA concepts by providing entirely new and original approaches to dynamic soft materials with internally encoded self-regulation features (similar to a self-destruction mechanism), opening doors to active functionalities and adaptive properties beyond what classical responsive equilibrium SA can offer.
Read more about such concepts in the 10th year anniversary issue of Soft Matter: "" Approaches to program the time domain of self-assemblies"" Soft Matter, 2015,11, 7857-7866"
Summary
"TimeProSAMAT aims to introduce concepts to program the time domain of self-assembled systems and materials in CLOSED systems under non-equilibrium conditions by controlling the kinetics of assembly and disassembly pathways via (i) modulating the surrounding by feedback systems, (ii) dissipative structure formation and (iii) active structural feedback. After reaching a fundamental understanding on a SA level, we want to capitalize on these enabling SA concepts by providing entirely new and original approaches to dynamic soft materials with internally encoded self-regulation features (similar to a self-destruction mechanism), opening doors to active functionalities and adaptive properties beyond what classical responsive equilibrium SA can offer.
Read more about such concepts in the 10th year anniversary issue of Soft Matter: "" Approaches to program the time domain of self-assemblies"" Soft Matter, 2015,11, 7857-7866"
Max ERC Funding
1 499 813 €
Duration
Start date: 2016-11-01, End date: 2021-10-31
Project acronym YlideLigands
Project Tailoring Ylidic Compounds as Ligands for Organometallic Chemistry
Researcher (PI) Viktoria Daeschlein-Gessner
Host Institution (HI) RUHR-UNIVERSITAET BOCHUM
Call Details Starting Grant (StG), PE5, ERC-2015-STG
Summary Lewis bases are a fundamental class of compounds that are of utmost importance in almost any chemical transformation. According to the HSAB concept, they determine important properties such as the stability or solubility of compounds or the selectivity of reactions. Yet, Lewis bases are used far beyond simple acid-base pairs. In coordination chemistry they act as efficient σ-donor ligands, which crucially affect the electronics of the metal and thus its reactivity. Additionally, bulky Lewis bases as part of Frustrated Lewis Pairs are applicable in bond activation reactions and also in catalysis. Typical Lewis bases are neutral compounds with a free pair of electrons, such as amines or phosphines. In contrast, carbon-centred Lewis bases such as carbenes have long been underestimated due to their usually high reactivity and sensitivity. Yet, the last decades have revealed a revolution in this context. Carbenes in particular have proven to be powerful reagents not only as ligands, but also in organocatalysis and bond activation chemistry. Bisylides and their dianionic congeners (methandiides) with formally two electron pairs at carbon are further classes of carbon bases that have started to find applications, but which are still profoundly underdeveloped.
This project takes aim at the development and application of novel ylidic, carbon-centred Lewis bases. By means of a smart molecular design, systems with unusual electronic properties and donor capacities will be prepared and their reactivity towards main group element compounds and transition metal complexes will be explored. Employing experimental and computational methods a fundamental understanding of the electronic structure and its influencing factors will be provided. This will allow a manipulation and tailoring of the properties and reactivities and thus open applications such as in bond activation reactions or their use as electronically flexible ligands in catalytically active metal complexes.
Summary
Lewis bases are a fundamental class of compounds that are of utmost importance in almost any chemical transformation. According to the HSAB concept, they determine important properties such as the stability or solubility of compounds or the selectivity of reactions. Yet, Lewis bases are used far beyond simple acid-base pairs. In coordination chemistry they act as efficient σ-donor ligands, which crucially affect the electronics of the metal and thus its reactivity. Additionally, bulky Lewis bases as part of Frustrated Lewis Pairs are applicable in bond activation reactions and also in catalysis. Typical Lewis bases are neutral compounds with a free pair of electrons, such as amines or phosphines. In contrast, carbon-centred Lewis bases such as carbenes have long been underestimated due to their usually high reactivity and sensitivity. Yet, the last decades have revealed a revolution in this context. Carbenes in particular have proven to be powerful reagents not only as ligands, but also in organocatalysis and bond activation chemistry. Bisylides and their dianionic congeners (methandiides) with formally two electron pairs at carbon are further classes of carbon bases that have started to find applications, but which are still profoundly underdeveloped.
This project takes aim at the development and application of novel ylidic, carbon-centred Lewis bases. By means of a smart molecular design, systems with unusual electronic properties and donor capacities will be prepared and their reactivity towards main group element compounds and transition metal complexes will be explored. Employing experimental and computational methods a fundamental understanding of the electronic structure and its influencing factors will be provided. This will allow a manipulation and tailoring of the properties and reactivities and thus open applications such as in bond activation reactions or their use as electronically flexible ligands in catalytically active metal complexes.
Max ERC Funding
1 500 000 €
Duration
Start date: 2016-07-01, End date: 2021-06-30
