Avviso di seminario del Prof. Daniele CASTAGNOLO (University College London) dal titolo

"Biocatalytic and chemo-enzymatic cascades for the synthesis of
heterocycles and sulfur compounds".

Biocatalysis is the use of natural enzymes, as isolate entities or as whole cells, for the synthesis of non-natural organic compounds and it probably represents the greenest technology for the manufacturing of fine chemicals and pharmaceutical ingredients under mild and sustainable conditions. The number of small and large industries employing biocatalysts for the manufacturing of drugs and chemicals has exponentially increased in the last decade due to the advantages that enzymes intrinsically offer in terms of stereo-, chemo- and regio-selectivity. In addition, the possibility to combine biocatalysis with classical chemocatalytic methods in a concurrent fashion (chemo-enzymatic cascades) represents an intriguing challenge for chemists and biologists as it allows to outperform sequential transformations with a higher degree of selectivity. Chemo-enzymatic cascade reactions can offer multiple benefits such as the immediate succession of individual transformations and the in-situ consumption of toxic or unstable intermediates without the requirement of intermediate isolation or functional group protection strategies, thus leading to safer processes and to the reduction of undesired side products.¹

Our research group aims at developing greener, scalable and sustainable methodologies for the synthesis of drugs and chemicals by replacing toxic and polluting reagents with enzymes, combining chemo- and biocatalysts in cascade reactions to avoid multiple purification steps and performing chemical reactions at mild temperatures and in the presence of benign solvents such water. In particular, we are interested in the development of novel biocatalytic and chemoenzymatic cascades to access aromatic heterocycles (pyrroles, indole, furans),^2-4 which constitute the core of most drugs and pharmaceutical ingredients, exploiting monoamine oxidase, laccase and peroxidase enzymes. In parallel, we are also interested in the discovery of novel biocatalysts for the synthesis of chiral sulfur compounds as flavours and fragrances and excipients in pharmaceutical preparations.^5-6

1) Zhao, F.; Masci, D.; Tomarelli, E.; Castagnolo, D. “Biocatalytic and Chemo-Enzymatic Approaches for the Synthesis of Heterocycles” Synthesis 2020, 52, 2948-2961; 2) Zhao, F.; Masci, D.; Ferla, S.; Varrichio, C.; Brancale, A.; Colonna, S.; Black, G. W.; Turner, N. J.; Castagnolo, D. “Monoamine Oxidase (MAO-N) Biocatalyzed Synthesis of Indoles from Indolines Prepared via Photocatalytic Cyclization/Arylative Dearomatization” ACS Catal. 2020, 10, 6414-6421. 3) Risi, C.; Zhao, F.; Castagnolo, D. “Chemo-Enzymatic Metathesis/Aromatization Cascades for the Synthesis of Furans: Disclosing the Aromatizing Activity of Laccase/TEMPO in Oxygen-Containing Heterocycles” ACS Catal. 2019, 9, 7264-7269. 4) Scalacci, N.; Black, Gary W.; Mattedi, G.; Brown, N.L.; Turner, N.J.; Castagnolo, D. “Unveiling the biocatalytic aromatizing activity of monoamino oxidases MAO-N and 6-HDNO: development of chemoenzymatic cascades for the synthesis of pyrroles” ACS Catal. 2017, 7, 1295-1300. 5) Anselmi, S.; Aggarwal, N.; Moody, T.S.; Castagnolo, D. “Unconventional biocatalytic approaches for the synthesis of chiral sulfoxides” ChemBioChem 2020, 22, 298-307. 6) Lauder, K.; Toscani, A.; Qi, Y.; Lim, J.; Charnock, S.J.; Korah, K.; Castagnolo, D. “Photo-biocatalytic one-pot cascades for the enantioselective synthesis of 1,3-mercaptoalkanol volatile sulfur compounds” Angew. Chem., Int. Ed. 2018, 57, 5803-5807. 7) Zhao, F.; Lauder, K.; Liu, S.; Finnigan, J.D.; Charnock, S.B.R.; Charnock, S.J.; Castagnolo, D. “Chemoenzymatic Cascades for the Enantioselective Synthesis of β-Hydroxysulfides Bearing a Stereocentre at the C−O or C−S Bond by Ketoreductases”, Angew. Chem., Int. Ed. 2022, in press.