15/03/2021

PhD in Chemistry

This job offer has expired


  • ORGANISATION/COMPANY
    Université de Montpellier
  • RESEARCH FIELD
    ChemistryOrganic chemistry
  • RESEARCHER PROFILE
    First Stage Researcher (R1)
  • APPLICATION DEADLINE
    15/05/2021 20:00 - Europe/London
  • LOCATION
    France › Montpellier
  • TYPE OF CONTRACT
    Temporary
  • JOB STATUS
    Full-time
  • HOURS PER WEEK
    40
  • OFFER STARTING DATE
    01/10/2021

OFFER DESCRIPTION

PhD Proposal – 2021-2024

Sustainable approaches for the synthesis of nucleotides and P-stereogenic derivatives

Nucleotides (5’-(poly)-phosphorylated nucleosides), their conjugates and analogues are organophosphorus compounds widely used as biological tools (DNA sequencing, cap analogues for in vitro synthesis of mRNAs,…).1 Moreover, many structural analogues interfere with the biosynthesis of nucleic acids, and hence are used as antiviral or anticancer drugs (administrated in their nucleoside form or as nucleotide prodrugs).2 For exemple, ProTides are very effective in the treatment of viral infections (Sofosbuvir/Hepatitis C) and harbor a chiral phosphorus atom as a special feature.3 The stereoselective synthesis of these P-stereogenic compounds usually involves the use of chiral auxiliaries or enantiopure chiral P-reagents.4

The aim of this project is to develop original and/or eco-compatible synthetic methods to gain access to nucleotides and derivatives based on the use of alternatives solvents for green chemistry (instead of N,N-dimethylformamide, N-methylpyrrolidinone chlorinated solvents) or mecanochemistry. The new molecules obtained will be valued through collaborations with external partners.

The first part of the thesis stems from our previous research,5 and will be devoted to the development of eco-compatible synthetic procedures to obtain dinucleoside 5’,5’-tetraphosphates as well as cap analogues. The second part will focus on the conception and the development of innovative methods to synthesize P-stereogenic compounds.

Keywords : Organic synthesis, phosphorus chemistry, stereoselectivity, green chemistry, dinucleotides, prodrugs.

Literature :

1) Roy, B.; Depaix, A.; Périgaud, C.; Peyrottes, S. Chem. Rev 2016, 116, 7854-7897.

2) Pastuch-Gawołek, G.; Gillner, D.; Król, E.; Walczak, K.; Wandzik, I. Eur. J. Pharmacol. 2019, 865, 172747.

3) Yu, H.; Yang, H.; Shi, E.; Tang, W. Medicine in Drug Discovery 2020, 8, 100063.

4) Lemouzy, S.; Giordano, L.; Hérault, D.; Buono, G. Eur. J. Org. Chem. 2020, 3351-3366.

5) Appy, L.; Depaix, A.; Bantreil, X.; Lamaty, F.; Peyrottes, S.; Roy, B. Chem.–Eur. J. 2019, 25, 2477–2481.

 

More Information

Offer Requirements

Skills/Qualifications

The candidate must hold a Master's degree in organic chemistry or equivalent. Knowledge in the chemistry of phosphorus biomolecules and/or analysis of biomolecules (NMR, MS, HPLC,...) will be a major advantage. Motivation, curiosity and autonomy are highly desirable qualities.

Work location(s)
1 position(s) available at
Institut des Biomolécules Max Mousseron
France
Montpellier

EURAXESS offer ID: 615903

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