Clay catalysed amidation of alcohols with nitriles in dry media

Montmorillonite KSF catalyses the Ritter reaction in which several benzyl, allyl and tertiary alcohols are converted into amides in high yields, when heated with various nitriles in the absence of solvent. A comparative study of conventional vs. microwave irradiation for this clay catalysed reaction is presented

Structures of SHV-1 β-lactamase with penem and penam sulfone inhibitors that form cyclic intermediates stabilized by carbonyl conjugation.

Bacterial β-lactamase enzymes are in large part responsible for the decreased ability of β-lactam antibiotics to combat infections. The inability to overcome β-lactamase mediated resistance spurred the development of inhibitors with penems and penam sulfones being amongst the most potent and broad spectrum mechanism-based inactivators. These inhibitors form covalent, "suicide-type" inhibitory intermediates that are attached to the catalytic S70 residue. To further probe the details of the mechanism of β-lactamase inhibition by these novel compounds, we determined the crystal structures of SHV-1 bound with penem 1, and penam sulfones SA1-204 and SA3-53. Comparison with each other and with previously determined crystal structures of members of these classes of inhibitors suggests that the final conformation of the covalent adduct can vary greatly amongst the complex structures. In contrast, a common theme of carbonyl conjugation as a mechanism to avoid deacylation emerges despite that the penem and penam sulfone inhibitors form different types of intermediates. The detailed insights gained from this study could be used to further improve new mechanism-based inhibitors of these common class A serine β-lactamases

Penem and penam sulfones and their reaction mechanisms.

<p>(A) Chemical structures of penem and penam sulfone compounds. (B) proposed inhibition mechanism by a penem <b>1</b> (based on Knox’s work and others) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0049035#pone.0049035-Nukaga1" target="_blank">[10]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0049035#pone.0049035-Venkatesan1" target="_blank">[11]</a>; carbon atoms labeled with * are the stereo centers; (C) proposed reaction mechanism of SA1-204.</p

Data collection and refinement statistics.

a<p>Numbers in parentheses refer to the highest resolution shell.</p>b<p>rmsd, root-mean-square deviation.</p

Electron density maps showing inhibitor density in SHV-1 active site (A) Left figure is the unbiased omit <i>F</i>o-<i>F</i>c map contoured at 3.0σ of SHV-1: penem 1 complex (B) anomalous difference Fourier map contoured at 3.5σ showing strong density peaks on top of the two sulfur atoms of penem 1 intermediate; (C) Unbiased omit <i>F</i>o-<i>F</i>c map contoured at 2.5σ of SHV-1:SA1-204 complex.

<p>(D) Unbiased omit <i>F</i>o-<i>F</i>c map contoured at 3σ of SHV-1:SA3-53 complex.</p

Minimum Inhibitory Concentrations (MICs) of Piperacillin (Pip) in Combination with 4 µg/ml Tazobactam (Tazo), and Penem 1.

<p>Minimum Inhibitory Concentrations (MICs) of Piperacillin (Pip) in Combination with 4 µg/ml Tazobactam (Tazo), and Penem 1.</p

Penam sulfone interactions in SHV-1 active site.

<p>(A) Stereo view of SA1-204 bound to SHV-1. (B) Stereo view of SA3-53 bound to SHV-1.</p