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Pharmaceutical Synthesis Unit

Macroarea: Organic Chemistry

ERC Sector: PE5_17 Organic chemistry

Research Team

Lab Managers: Marcello Di Giacomo (RU)

Research Line

The research activity of the Pharmaceutical Synthesis Unit is primarily aimed at the total synthesis of biologically active natural substances and the synthesis of compounds of pharmaceutical interest. Particular attention is given to the preparation of enantiomerically pure substances through the application of asymmetric synthesis techniques (chiral organometallic catalysts, chiral auxiliaries, and organocatalysis). The research activity is also focused on the scale-up of synthetic processes to obtain bioactive compounds in quantities and purities suitable for preclinical experimentation. This activity involves the preparation of final products on the scale of tens of grams, and thus requires the implementation of efficient and easily scalable purification processes, such as the resolution of racemic mixtures through fractional crystallization.

The experience gained over the years in organic synthesis is transversally applicable to various pharmaceutical chemistry projects, from the synthesis of compounds on a small scale for preliminary biological study, to the preparation of lead compounds in sufficient quantities for an in-depth investigation of the pharmacodynamic and pharmacokinetic profile in in vivo models. The activity is predominantly conducted in close collaboration with the MedChem Lab team. This allows for operation in a highly multidisciplinary context, aimed at obtaining molecules with high therapeutic potential.

Currently, the Pharmaceutical Synthesis Unit relies on the pharmaceutical chemistry laboratory, coordinated by Professor Collina. Soon, the unit will have a laboratory dedicated to organic synthesis, equipped with the appropriate apparatus for carrying out organic synthesis projects, on a bench scale (tens to hundreds of mg) and for a first scale-up (on the order of 100 g).

Publications
  • Volpe, S.D., Listro, R., Parafioriti, M., Di Giacomo, M., Rossi, D., Ambrosio, F.A., Costa, G., Alcaro, S., Ortuso, F., Hirsch, A.K.H., Vasile, F., Collina, S.; BOPC1 Enantiomers Preparation and HuR Interaction Study. From Molecular Modeling to a Curious DEEP-STD NMR Application; (2020) ACS Medicinal Chemistry Letters, 11 (5), pp. 883-888.
  • Della Volpe, S., Nasti, R., Queirolo, M., Unver, M.Y., Jumde, V.K., Dömling, A., Vasile, F., Potenza, D., Ambrosio, F.A., Costa, G., Alcaro, S., Zucal, C., Provenzani, A., Di Giacomo, M., Rossi, D., Hirsch, A.K.H., Collina, S.; Novel Compounds Targeting the RNA-Binding Protein HuR. Structure-Based Design, Synthesis, and Interaction Studies; (2019) ACS Medicinal Chemistry Letters, 10 (4), pp. 615-620.
  • Malacrida, A., Cavalloro, V., Martino, E., Cassetti, A., Nicolini, G., Rigolio, R., Cavaletti, G., Mannucci, B., Vasile, F., Di Giacomo, M., Collina, S., Miloso, M.; Anti-multiple myeloma potential of secondary metabolites from hibiscus sabdariffa; (2019) Molecules, 24 (13), art. no. 2500.
  • Rossino, G., Raimondi, M.V., Rui, M., Di Giacomo, M., Rossi, D., Collina, S.;  PEG 400/cerium ammonium nitrate combined with microwave-assisted synthesis for rapid access to beta-amino ketones. an easy-to-use protocol for discovering new hit compounds; (2018) Molecules, 23 (4), art. no. 775
  • Rossi, D., Rui, M., Di Giacomo, M., Schepmann, D., Wünsch, B., Monteleone, S., Liedl, K.R., Collina, S.; Gaining in pan-affinity towards sigma 1 and sigma 2 receptors. SAR studies on arylalkylamines; (2017) Bioorganic and Medicinal Chemistry, 25 (1), pp. 11-19.
  • Serra, M., Tambini, S.M., Di Giacomo, M., Peviani, E.G., Belvisi, L., Colombo, L.; Synthesis of Easy-to-Functionalize Azabicycloalkane Scaffolds as Dipeptide Turn Mimics en Route to cRGD-Based Bioconjugates; (2015) European Journal of Organic Chemistry, 2015 (34), pp. 7557-7570.
  • Di Giacomo, M., Serra, M., Brusasca, M., Colombo, L.; Stereoselective Pd-catalyzed synthesis of quaternary α-d-C-mannosyl- (S)-amino acids; (2011) Journal of Organic Chemistry, 76 (13), pp. 5247-5257.
  • Colombo, L., Di Giacomo, M., Serra, M., Tambini, S.M.; Novel stereoselective syntheses of (2E,4E)-4-(4,4-dimethylpent-2-ynylidene)-N1,N5-dimethyl-N1,N5-bis(naphthalen-1-ylmethyl)pent-2-ene-1,5-diamine; (2009) Tetrahedron, 65 (29-30), pp. 5838-5843.
  • Di Giacomo, M., Vinci, V., Serra, M., Colombo, L.; New fast and practical method for the enantioselective synthesis of α-vinyl, α-alkyl quaternary α-amino acids; (2008) Tetrahedron Asymmetry, 19 (2), pp. 247-257.
  • Alcaro, M.C., Vinci, V., D'Ursi, A.M., Scrima, M., Chelli, M., Giuliani, S., Meini, S., Di Giacomo, M., Colombo, L., Papini, A.M.; Bradykinin antagonists modified with dipeptide mimetic β-turn inducers; (2006) Bioorganic and Medicinal Chemistry Letters, 16 (9), pp. 2387-2390.
Collaborations

National collaborations

S. Collina (Dipartimento di Scienze del Farmaco - Università di Pavia), E. Martino (Dipartimento di Scienze della Terra e dell’Ambiente – Università di Pavia)