News

Published an efficient method for the synthesis of 3-hydroxymethyl isoindolinones

Dr. Grigorjeva et.al. (Organic Synthesis Methodology group) have developed an efficient method for the synthesis of 3-hydroxymethyl isoindolinones via cobalt-catalyzed C(sp2)–H carbonylation of phenylglycinol derivatives using picolinamide as a traceless directing group.

Authors have demonstrated synthetic route that offers a broad substrate scope, excellent regioselectivity, and full preservation of the original stereochemistry providing a pathway for accessing valuable enantiopure 3-substituted isoindolinone derivatives.

This method is published in the high- impact ACS journal – Organic Letters (IF=6.555, 2018):

Lukass Lukasevics, Aleksandrs Cizikovs, Liene Grigorjeva*
Synthesis of 3-Hydroxymethyl Isoindolinones via Cobalt-Catalyzed C(sp2)–H Carbonylation of Phenylglycinol Derivatives. Org. Lett. 2020, DOI: 10.1021/acs.orglett.0c00672

Grigorjeva_OrgLett_03.2020

This research was financially supported by ERDF project Nr.1.1.1.5/17/A/004.

Novel method for cobalt catalyzed C(sp2)-H functionalization of phenylglycinol derivatives

Dr. Grigorjeva et.al. (Organic Synthesis Methodology group) have developed a new method for cobalt catalyzed C(sp2)-H functionalization of phenylglycinol derivatives with terminal and internal alkynes directed by picolinamide auxiliary. Elaborated method offers an efficient and highly regioselective route for the synthesis of 1-hydroxymethyltetrahydroisoquinolines.

The Journal of Organic Chemistry (IF=4.745, 2018) accepted this methodology for publication:

Jekaterina Bolsakova, Lukass Lukasevics, Liene Grigorjeva*
Cobalt-catalyzed, directed C-H functionalization/annulation of phenylglycinol derivatives with alkynes. J. Org. Chem. 2020, DOI: 10.1021/acs.joc.0c00207

jo0c00207_0010-2

This research was financially supported by ERDF project Nr.1.1.1.5/17/A/004.

Published studies on new phosphorescent dopants

Scientists from the Pharmacomodulators Synthesis group (LIOS) together with authors from the Kaunas University of Technology, KTH Royal Institute of Technology, Bohdan Khmelnytsky National University published a joint article on new phosphorescent dopants for hybrid solution-processable OLEDs.

Authors described the synthesis phosphorescent platinum complexes bearing 2- and 3-(2-pyridyl)benzo[b]selenophenes (PyBSe). Compounds are fully characterized. Observed that the solid solutions of novel platinum complexes emitted efficient green and red phosphorescence with AQY of 52% (for green) and 11.6% (for red).

The article is published in the journal “Dalton Transactions” (IF= 4.052, 2018):

Petrenko A., Leitonas K., Volyniuk D., Baryshnikov G.V., Belyakov S., Minaev B. F., Ågren H., Durgaryan H., Gražulevičius J.V.,  Arsenyan P.
Benzoselenophenylpyridine platinum complexes: green versus red phosphorescence towards hybrid OLEDs.
Dalton Trans., 2020, DOI: 10.1039/D0DT00214C

Arsenyan_Dalton_trans_02.2020

Alliance4Life released White Paper providing new view on innovation gap

Alliance4Life, in line with its mission to help closing the divide in European health research and innovation (R&I), provides a new picture on the R&I gap in Europe by using the comparison of GERD (gross domestic expenditure on research and development) and top 10% publications. The selection of these two indicators gives more visibility to the fact that the origin of innovation lies in excellent science.

Alliance4Life considers the following three factors as the key for speeding up the process of closing the R&I divide in Europe:

  • Critical level of financing
  • Good governance
  • Cultural factors

Based on the national roundtables with research policymakers organized in all Alliance4Life´s countries of Central and Eastern Europe, recommendations for the improvement in the following six areas are being suggested to the national and EU policymakers:

    • Concertation of research capacities and support of research excellence
    • Effective management and financing of Research Infrastructures
    • Modern Human Resource management and career system
    • Up-to-date governance of research institutions
    • National financing structure and grant system supporting excellence
    • Development and recognition of professional research administration

Alliance4Life White Paper for DOWNLOAD

A4L_White paper_2020

New article in the field of materialsciences

Scientists from the Pharmacomodulators Synthesis group together with authors from the Kaunas University of Technology published a joint article on the synthesis of fused chalcogenophenocarbazoles bearing a trimethylsilylpropyl substituent at the nitrogen atom of carbazole.

The compounds were characterized by fluorescence resulting from recombination of either locally excited, intramolecular charge-transfer or hybridized local and charge-transfer (HLCT) states. This is the first report on dual emission of HLCT character observed for S or Se-carbazoles.

The article is published in the journal New Journal of Chemistry (IF=3.069, 2018):

A. Petrenko, O. Bezvikonnyi, D. Volyniuk, Y. Danyliv, J. Simokaitiene, S. Belyakov,   J. V. Grazulevicius, P. Arsenyan.
Synthesis of fused chalcogenophenocarbazoles: towards dual emission resulting from hybridized local and charge-transfer states
New J. Chem., 2020, DOI: 10.1039/C9NJ06211D

Arsenyan_New_J_Chem_2020-Feb

Review on mitochondrial function in the insulin-resistant heart

Scientists from the Laboratory of Pharmaceutical Pharmacology together with authors from 7 other countries published a joint review on how mitochondria are functioning in the insulin-resistant heart. Authors described changes in energy metabolism and mitochondrial function in the diabetic heart as well as highlighted possible treatment strategies. The review is published in the journal Acta Physiologica (IF=5.868, 2018):

M. Makrecka‐Kuka, E. Liepinsh, A. J. Murray, H. Lemieux, M. Dambrova, K. Tepp, M. Puurand, T. Käämbre, W. H. Han, P. de Goede, K. A. O’Brien, B. Turan, E. Tuncay, Y. Olgar, A. P. Rolo, C. M. Palmeira, N. T. Boardman, R. C. I. Wüst, T. S. Larsen.

Altered mitochondrial metabolism in the insulin-resistant heart.
Acta Physiologica 2019, Article number e13430, DOI: 10.1111/apha.13430

This publication is based upon work from COST Action CA15203 MITOEAGLE, supported by COST (European Cooperation in Science and Technology). EL was supported by the Latvian Council of Science grant project No.lzp-2018/1-0082.

Published methodology of Johnson–Corey–Chaykovsky fluorocyclopropanation reaction

Dr. Veliks et.al. have published a synthetic methodology of synthesis of a range of monofluoro-cyclopropane derivatives in the journal “Organic & Biomolecular Chemistry” (IF=3.490, 2018). Authors demonstrated Johnson–Corey–Chaykovsky fluorocyclopropanation of double activated alkenes utilizing S-monofluoromethyl-S-phenyl-2,3,4,5-tetramethylphenylsulfonium tetrafluoroborate:

Armands Kazia, Renate Melngaile, Anatoly Mishnev, Janis Veliks*
Johnson–Corey–Chaykovsky fluorocyclopropanation of double activated alkenes: scope and limitations. Org. Biomol. Chem., 2020,DOI: 10.1039/C9OB02712B

Veliks_Org.Biomol.Chem

ERA4TB, an international consortium to accelerate the development of comprehensive treatments against tuberculosis

More than 30 partners from 13 countries participate in the ERA4TB project

The ERA4TB (European Regimen Accelerator for Tuberculosis) project is a public-private initiative dedicated to the development of drugs against tuberculosis. With a team of more than thirty organizations and a budget of over 200 million euros, ERA4TB will focus on developing a new, improved tuberculosis treatment. The partners will share their expertise, knowledge and resources to rapidly progress new candidate drugs into clinical trials.

Tuberculosis is the leading cause of death by an infectious disease worldwide. According to the World Health Organization (WHO), an estimated 10 million people became ill with tuberculosis in 2018, and 1.6 million died. Even though the incidence of tuberculosis is declining, the drug-resistant form constitutes a growing threat to the safety of the world’s population. It is in this spirit that the UN has pledged to end the tuberculosis epidemic by 2030 through joint action of its member states.

David Barros-Aguirre, Project Lead for ERA4TB and VP and Head of Tuberculosis Research, Global Health R&D, GSK said: “On behalf of the ERA4TB partners, we are very excited about the start of this unique collaborative project in the field of tuberculosis where the expertise from public partners and a pipeline of promising preclinical candidates from pharmaceutical companies merge to accelerate the development of novel clinical candidates. The goal is to deliver an innovative and differentiated combination regimen for the treatment of TB, which can play a key role in the elimination agenda.”

Standard tuberculosis treatment is based on a combination regimen of four drugs that were all developed more than 60 years ago. The treatment lasts for at least six months and, in the case of resistance to the standard drugs, can be as long as two years. The current drugs are inefficient by today’s standards and a new, faster-acting and safer treatment is required to reduce the length of therapy and to overcome the menace of drug-resistant strains. Until now, the development of new drugs has been slow and their incorporation into tuberculosis treatment regimens conducted in a sequential manner.

Stewart Cole, Scientific leader of ERA4TB and President of the Institut Pasteur, said “ERA4TB has assembled an impressive array of resources to seamlessly harness the agility and innovation of academia with the pragmatism and scientific expertise of pharma. I am confident that this powerful European initiative will speed the path to TB elimination.”

ERA4TB is set to change the paradigm of tuberculosis treatment development by abandoning the sequential approach in favor of a parallel pathway, which will allow the simultaneous investigation of more than a dozen drug candidates. By implementing a standardized approach to tuberculosis drug development, that is well coordinated with the collaborations outside Europe, ERA4TB has the potential to optimize, and, more importantly, greatly reduce the development times of the new regimens needed to eliminate this epidemic.

According to Juan José Vaquero, project coordinator from UC3M (University Carlos III Madrid) and leader of the imaging team, “ERA4TB will change the paradigm for the development of new TB drugs by adopting a flexible and modular collaboration scheme in which research efforts can be rapidly mobilized to where they are most needed allowing several molecules to be investigated simultaneously. This will save both time and money.”

Latvian Institute of Organic Synthesis (IOS) is an independent public research organization doing research in chemical biology with a strong focus on drug discovery and preclinical development. IOS possesses a broad spectrum of expertise including medicinal chemistry, organic synthesis, in vitro and in vivo pharmacology, bioanalytical studies, computational modelling, biophysical chemistry and process chemistry.

For project ERA4TB, IOS will contribute with its process chemistry capacities by developing cost-effective manufacturing routes of candidate drugs.

ERA4TB is sponsored by the European Union’s Horizon 2020 research and innovation programme and the European pharmaceutical industry (via EFPIA) under the auspices of the Innovative Medicines Initiative 2 Joint Undertaking and part of the AMR Accelerator umbrella.

About the Innovative Medicines Initiative

The Innovative Medicines Initiative (IMI) is Europe’s largest public-private initiative aiming to speed up the development of better and safer medicines for patients. IMI supports collaborative research projects and builds networks of industrial and academic experts in order to boost pharmaceutical innovation in Europe. IMI is a joint undertaking between the European Union and the European Federation of Pharmaceutical Industries and Associations, EFPIA.

More information can be found at www.imi.europa.eu

Acknowledgement

This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 853989. The JU receives support from the European Union’s Horizon 2020 research and innovation programme, and in-kind support from EFPIA, TB Alliance, Bill & Melinda Gates Foundation and the University Of Dundee.

EU_flag IMI_new efpia
BILL TB_alliance uni_of_Dundee

Disclaimer

This communication reflects the views of the ERA4TB Consortium and neither IMI nor the European Union and EFPIA are liable for any use that may be made of the information contained herein.

CONTACTS:

Project Leader: David Barros-Aguirre ()
Project Coordinator: Juan Jose Vaquero Lopez ()
Scientific Leader: Stewart Cole ()

Novel method for characterization of insulin sensitivity

Despite extensive research efforts, very few markers are used in clinics for the diagnosis of type 2 diabetes mellitus. While fatty acid intermediates have been studied in diabetes patients and experimental models of insulin resistance, none of these markers have been successfully translated into clinical practice.

Authors from the Latvian Institute of Organic Synthesis show that a blunted decrease in long-chain acylcarnitine plasma concentrations during the glucose tolerance test is associated with muscle-specific insulin resistance, while postprandial changes in plasma FFA levels reflect adipose tissue insulin sensitivity. Authors propose that implementation of FFAs and long-chain acylcarnitine measurements would provide multiple clinical benefits. This diagnostic approach would provide novel possibilities to characterize tissue-specific insulin resistance during diabetes progression and intervention (both lifestyle changes and pharmacotherapy).

The research has been published in Frontiers in Endocrinology (IF=3.634):

E. Makarova, M. Makrecka-Kuka, K. Vilks, Kristine Volska, Eduards Sevostjanovs, Solveiga Grinberga, Olga Zarkova-Malkova, Maija Dambrova and Edgars Liepinsh
Decreases in Circulating Concentrations of Long-Chain Acylcarnitines and Free Fatty Acids During the Glucose Tolerance Test Represent Tissue-Specific Insulin Sensitivity
Front. Endocrinol., 2019, DOI: 10.3389/fendo.2019.00870

fendo-10-00870-g006

 

New studies on selenocystine peptides

Dr. Pavel Arsenyan group showed a new approach for the generation of selenocysteinyl electrophile by weak Lewis acids or oxidants. The elaborated protocol allows the construction of phenylindeno[1,2‐ c ]chromene moiety in 5‐ endo‐dig /6‐ endo‐dig cascade reactions. This method is published in the European Journal of Organic Chemistry (IF 3.029):

Sindija Lapcinska, Pavel Arsenyan.
Selenocystine peptides performance in 5‐endo‐dig reactions.
Eur. J. Org. Chem., 2020, DOI: 10.1002/ejoc.201901548

Arsenyan_Eur.J.Org.Chem_2020-2

The research was supported by Latvian Institute of Organic Synthesis internal student grant IG-2018-06.