5470-80-4Relevant articles and documents
Effect of the Heteroaromatic Antenna on the Binding of Chiral Eu(III) Complexes to Bovine Serum Albumin
De Rosa, Chiara,Melchior, Andrea,Sanadar, Martina,Tolazzi, Marilena,Giorgetti, Alejandro,Ribeiro, Rui P.,Nardon, Chiara,Piccinelli, Fabio
, p. 12564 - 12577 (2020)
The cationic enantiopure (R,R) and luminescent Eu(III) complex [Eu(bisoQcd)(H2O)2] OTf (with bisoQcd = N,N′-bis(2-isoquinolinmethyl)-trans-1,2-diaminocyclohexane N,N′-diacetate and OTf = triflate) was synthesized and characterized. At physiological pH, the 1:1 [Eu(bisoQcd)(H2O)2]+ species, possessing two water molecules in the inner coordination sphere, is largely dominant. The interaction with bovine serum albumin (BSA) was studied by means of several experimental techniques, such as luminescence spectroscopy, isothermal titration calorimetry (ITC), molecular docking (MD), and molecular dynamics simulations (MDS). In this direction, a ligand competition study was also performed by using three clinically established drugs (i.e., ibuprofen, warfarin, and digitoxin). The nature of this interaction is strongly affected by the type of the involved heteroaromatic antenna in the Eu(III) complexes. In fact, the presence of isoquinoline rings drives the corresponding complex toward the protein superficial area containing the tryptophan residue 134 (Trp134). As the main consequence, the metal center undergoes the loss of one water molecule upon interaction with the side chain of a glutamic acid residue. On the other hand, the similar complex containing pyridine rings ([Eu(bpcd)(H2O)2]Cl with bpcd = N,N′-bis(2-pyridylmethyl)-trans-1,2-diaminocyclohexane N,N′-diacetate) interacts more weakly with the protein in a different superficial cavity, without losing the coordinated water molecules.
Biocatalytic reduction of α,β-unsaturated carboxylic acids to allylic alcohols
Aleku, Godwin A.,Leys, David,Roberts, George W.
, p. 3927 - 3939 (2020/07/09)
We have developed robust in vivo and in vitro biocatalytic systems that enable reduction of α,β-unsaturated carboxylic acids to allylic alcohols and their saturated analogues. These compounds are prevalent scaffolds in many industrial chemicals and pharmaceuticals. A substrate profiling study of a carboxylic acid reductase (CAR) investigating unexplored substrate space, such as benzo-fused (hetero)aromatic carboxylic acids and α,β-unsaturated carboxylic acids, revealed broad substrate tolerance and provided information on the reactivity patterns of these substrates. E. coli cells expressing a heterologous CAR were employed as a multi-step hydrogenation catalyst to convert a variety of α,β-unsaturated carboxylic acids to the corresponding saturated primary alcohols, affording up to >99percent conversion. This was supported by the broad substrate scope of E. coli endogenous alcohol dehydrogenase (ADH), as well as the unexpected CC bond reducing activity of E. coli cells. In addition, a broad range of benzofused (hetero)aromatic carboxylic acids were converted to the corresponding primary alcohols by the recombinant E. coli cells. An alternative one-pot in vitro two-enzyme system, consisting of CAR and glucose dehydrogenase (GDH), demonstrates promiscuous carbonyl reductase activity of GDH towards a wide range of unsaturated aldehydes. Hence, coupling CAR with a GDH-driven NADP(H) recycling system provides access to a variety of (hetero)aromatic primary alcohols and allylic alcohols from the parent carboxylates, in up to >99percent conversion. To demonstrate the applicability of these systems in preparative synthesis, we performed 100 mg scale biotransformations for the preparation of indole-3-aldehyde and 3-(naphthalen-1-yl)propan-1-ol using the whole-cell system, and cinnamyl alcohol using the in vitro system, affording up to 85percent isolated yield.
Microwave-promoted synthesis of N-heterocycles by tandem imination/ annulation of γ- and δ-ketoalkynes in the presence of ammonia
Alfonsi, Maria,Dell'Acqua, Monica,Facoetti, Diego,Arcadi, Antonio,Abbiati, Giorgio,Rossi, Elisabetta
experimental part, p. 2852 - 2862 (2009/09/06)
The synthesis of 3-substituted l-methylpyrrolo[l,2-a]pyrazines and 3-substituted isoquinolines was achieved by the intramolecular cyclisation of 2-acetyl-l-propargylpyrroles and 2-alkynylbenzaldehydes, respectively, in the presence of ammonia under microwave heating. The tandem imination/annulation of 2-alkynylbenzaldehydes was easily accomplished under standard conditions, while TiCl4 was used to achieve pyrrolo[l,2-a]pyrazines. The reaction mechanism and the regioselectivity were discussed on the basis of theoretical calculations and spectroscopic data. Wiley-VCH Verlag GmbH & Co. KGaA.
