Contacts:
E-mail:
ORCID: https://orcid.org/0000-0001-7239-115X
Scopus ID: 57205218493
Supervisors:
Prof. Anna Iuliano, Prof Lorenzo Guazzelli
Title:
Exploiting chirality of isohexide scaffolds: synthesis, characterization and applications of new chiral auxiliaries from isomannide and isosorbide
Abstract:
In the last years, a great deal of interest has been directed toward the use of biomass derived molecules. In the field of asymmetric synthesis and recognition, the use of the Chiral Pool was widespread. The exploit of such starting materials offers great advantages for the synthesis of new chiral compounds, such as the use of cheap starting materials available as enantiopure and easy to derivatize.
Among the compounds belonging to the chiral pool, (3R, 3aR, 6R, 6aR)-hexahydrofuro[3,2-b]furan-3,6-diol and (3R, 3aR, 6S, 6aR)-hexahydrofuro[3,2-b]furan-3,6-diol, also known as isomannide and isosorbide respectively, were widely employed in asymmetric synthesis and enantiomeric recognition.
Isomannide and isosorbide are two sugar-derived compounds, obtained from the dehydration of mannitol and sorbitol respectively; these sugars are byproducts of the starch industry and are obtained during the processing of the corn oil. In the last years, isomannide and isosorbide have been employed particularly in polymer, cosmetic and pharmaceutical industry. These compounds are renewable, cheap, available as enantiopure and easy to functionalize. In particular, each one of them possess two hydroxyl groups, both endo in isomannide and one endo (C3) and the other exo (C6) in isosorbide and the derivatization of one or both these functional groups leads to a set of chiral products whose properties depend not only on the nature of the introduced functional groups but also on their stereochemistry. Furthermore, the three-dimesional structure of these compounds constitutes chiral cavity; as a matter of fact, the cis junction of the two tetrahydrofuran rings confers them a vaulted structure with the endo OHs pointing in it. Starting from these considerations, the aim of the project is to synthesize new chiral selectors starting from isomannide and isosorbide, exploiting their chiral vaulted structure to facilitate the enantiodiscrimination through an enantioselective inclusion-like phenomena and the easy functionalization of the OHs to introduce functional groups able to enhance intermolecular interactions between the chiral selectors and the enantiomers of a substrate.
Publications:
1) Valerio Zullo, Anna Iuliano, “Rh‐catalyzed enantioselective conjugate addition of arylboronic acids to 3‐arylpropenoates: enantioselective synthesis of (R)‐Tolterodine”; EurJoc, 2019, 6, 1377.
https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/ejoc.201801690
2) Marcin Górecki, Valerio Zullo, A. Iuliano, G. Pescitelli, “On the Absolute Stereochemistry of Tolterodine: A Circular Dichroism Study”; Pharmaceuticals, 2019, 12(1), 21.
https://www.mdpi.com/1424-8247/12/1/21
3) Philippe Schwaller, Riccardo Petraglia, Valerio Zullo, Vishnu H Nair, Rico Andreas Haeuselmann, Riccardo Pisoni, Costas Bekas, Anna Iuliano and Teodoro Laino “Predicting Retrosynthetic Pathways using Transformer-Based Models and a Hyper-Graph Exploration Strategy”; Chemical Science, 2020, 11, 3316-3325
https://pubs.rsc.org/en/content/articlelanding/2020/sc/c9sc05704h#!divAbstract
4) Valerio Zullo, Marcin Górecki, Lorenzo Guazzelli, Andrea Mezzetta, Gennaro Pescitelli, Anna Iuliano “Exploiting isohexide scaffolds for the preparation of chiral ionic liquids tweezers”; Journal of Molecular Liquids, 2021, 322, 1145282
https://www.sciencedirect.com/science/article/pii/S0167732220345712
5) Valerio Zullo, Anna Iuliano, Lorenzo Guazzelli “Sugar-Based Ionic Liquids: Multifaceted Challenges and Intriguing Potential”; Molecules, 2021, 26(7), 2052.
https://doi.org/10.3390/molecules26072052
Oral communications at congress:
• “Il sogno di Mendeleev: tra previsioni e realtà”- 07/06/2019, Nell’ambito dell’iniziativa organizzata dal XXIV ciclo di dottorandi della Scuola di dottorato in Scienze Chimiche e Dei Materiali (DSCM) per i 150 anni della tavola periodica degli elementi
• “Synthesis of novel chiral ionic organic compounds from Isohexides as potential chiral selectors for Enantioselective Electroanalysis”, 25th November 2019, MYCS-Merck Young Chemists’ Symposium, Hotel Ambasciatori Rimini (Italy)
• “Synthesis and characterization of new chiral ionic liquids tweezers from isomannide and isosorbide”, 2th September 2020, International School of Chemistry (web edition)-Chemistry for everyday life, University of Camerino (Italy).
Poster communications at congress:
• “The Mendeleev's dream: between forecasts and reality”, A. Bonini, M. Bondanza, R. Francischello, D. Iacopini, F. Nardella, M. Nottoli, E. Parodi, S. Pizzimenti, D. Santalucia, S. Schoch, F. Vivaldi, V. Zullo, 07/06/2019, Nell’ambito dell’iniziativa organizzata dal XXIV ciclo di dottorandi della Scuola di dottorato in Scienze Chimiche e Dei Materiali (DSCM) per i 150 anni della tavola periodica degli elementi.
• “Rh-Catalyzed Asymmetric Conjugate Addition of Arylboronic Acids to 3-Arylpropenoates: Enantioselective Synthesis of (R)-Tolterodine” Valerio Zullo Anna Iuliano, ISOS 2019 (XLIV "A. Corbella" International Summer School on Organic Synthesis, Gargnano (Italy), 9th-13th June 2019)
• “Rh-Catalyzed Asymmetric Conjugate Addition of Arylboronic Acids to 3-Arylpropenoates: Enantioselective Synthesis of (R)-Tolterodine” Valerio Zullo Anna Iuliano, CFF 2019 - Chemistry for the Future- International Conference (July 3-5, 2019- Dipartimento di Chimica e Chimica Industriale, Via Giuseppe Moruzzi, 13 – Pisa)
