142387-15-3Relevant academic research and scientific papers
Using heteroaryl-lithium reagents as hydroxycarbonyl anion equivalents in conjugate addition reactions with (S, S)-(+)-pseudoephedrine as chiral auxiliary; Enantioselective synthesis of 3-substituted pyrrolidines
Alonso, Beatriz,Ocejo, Marta,Carrillo, Luisa,Vicario, Jose L.,Reyes, Efraim,Uria, Uxue
, p. 614 - 627 (2013/03/13)
We have developed an efficient protocol for carrying out the stereocontrolled formal conjugate addition of hydroxycarbonyl anion equivalents to α,β-unsaturated carboxylic acid derivatives using (S,S)-(+)-pseudoephedrine as chiral auxiliary, making use of the synthetic equivalence between the heteroaryl moieties and the carboxylate group. This protocol has been applied as key step in the enantioselective synthesis of 3-substituted pyrrolidines in which, after removing the chiral auxiliary, the heteroaryl moiety is converted into a carboxylate group followed by reduction and double nucleophilic displacement. Alternatively, the access to the same type of heterocyclic scaffold but with opposite absolute configuration has also been accomplished by making use of the regio- and diastereoselective conjugate addition of organolithium reagents to α,β,γ,δ-unsaturated amides derived from the same chiral auxiliary followed by chiral auxiliary removal, ozonolysis, and reductive amination/intramolecular nucleophilic displacement sequence.
Structural basis for the broad-spectrum inhibition of metallo-β- lactamases by thiols
Lienard, Benoit M. R.,Garau, Gianpiero,Horsfall, Louise,Karsisiotis, Andreas I.,Damblon, Christian,Lassaux, Patricia,Papamicael, Cyril,Roberts, Gordon C. K.,Galleni, Moreno,Dideberg, Otto,Frere, Jean-Marie,Schofield, Christopher J.
experimental part, p. 2282 - 2294 (2009/02/02)
The development of broad-spectrum metallo-β-lactamase (MBL) inhibitors is challenging due to structural diversity and differences in metal utilisation by these enzymes. Analysis of structural data, followed by non-denturing mass spectrometric analyses, identified thiols proposed to inhibit representative MBLs from all three sub-classes: B1, B2 and B3. Solution analyses led to the identification of broad spectrum inhibitors, including potent inhibitors of the CphA MBL (Aeromonas hydrophila). Structural studies revealed that, as observed for other B1 and B3 MBLs, inhibition of the L1 MBL thiols involves metal chelation. Evidence is reported that this is not the case for inhibition of the CphA enzyme by some thiols; the crystal structure of the CphA-Zn-inhibitor complex reveals a binding mode in which the thiol does not interact with the zinc. The structural data enabled the design and the production of further more potent inhibitors. Overall the results suggest that the development of reasonably broad-spectrum MBL inhibitors should be possible.
Towards the synthesis of calyculin: A synthetic intermediate corresponding to the C(26)-C(37) fragment
Vaccaro,Levy,Sawabe,Jaetsch,Masamune
, p. 1937 - 1940 (2007/10/02)
The synthetic intermediate 2 corresponding to the C(26)-C(37) fragment of calyculin A (1) has been synthesized. Key transformations include the efficient one-pot construction of the oxazole system embedded in 1 without epimerization α [C(30)] to the ring,
