Silver was widely used in medicine to treat bacterial infections in the 19th and early 20th century, up until the discovery and development of the first modern antibiotics in the 1940s, which were markedly more effective. Since then, every new antibiotic introduced to the clinic has led to an associated development of drug resistance. Today, the threat of extensive bacterial resistance to antibiotics has reignited interest in alternative strategies to treat infectious diseases, with silver regaining well-deserved renewed attention. Silver ions are highly disruptive to bacterial integrity and biochemical function, with comparatively minimal toxicity to mammalian cells. This review focuses on the antimicrobial properties of silver and their use in synergistic combination therapy with traditional antibiotic drugs.
Chiral secondary amines are valuable catalysts for reactions that proceed through an enamine intermediate. Here, we explored the importance of the pyramidalization direction of the enamine-N on the reactivity of chiral enamines with a combination of computational, NMR spectroscopic, and kinetic experiments. Studies with peptidic catalysts that bear cyclic amines with different ring sizes revealed that endo-pyramidalized enamines are significantly more reactive compared to exo-pyramidalized analogs. The results show that the pyramidalization direction can have a greater effect than n/p* orbital overlap on the reactivity of chiral enamines. The data enabled the development of a catalyst with higher reactivity compared to the parent catalyst. Scheme 1 (a) Secondary amine catalyzed addition reaction of aldehydes to electrophiles. (b) Anti-attack of enamine. (c) Equilibrium between endo and exo pyramidalized enamines. Scheme 2 (a) Conjugate addition reaction of butanal to nitrostyrene catalyzed by 2a, 2 and 2b. (b) In situ IR monitoring of the formation of g-nitroaldehyde, and (c) Arrhenius plot and activation energy of the peptide catalyzed reactions.This journal is
Stereoselective organocatalytic C−C bond formations that tolerate N‐heterocycles are valuable since these moieties are common motifs in numerous chiral bioactive compounds. Such transformations are, however, challenging since N‐heterocyclic moieties can interfere with the catalytic reaction. Here, we present a peptide that catalyzes conjugate addition reactions between aldehydes and nitroolefins bearing a broad range of different N‐heterocyclic moieties with basic and/or H‐bonding sites in excellent yields and stereoselectivities. Tuning of the pyramidalization direction of the enamine intermediate enabled the high stereoselectivity.
Bioorthogonal reactions have emerged as a versatile tool in life sciences. The inverse electron demand Diels-Alder reaction (DA ) stands out due to the availability of reactants with very fast kinetics. However, highly reactive dienophiles suffer the disadvantage of being less stable and prone to side reactions. Herein, we evaluate the extent of acceleration of rather unreactive but highly stable dienophiles by DNA-templated proximity. To this end, we developed a modular synthetic route for a novel bifunctional fluorogenic tetrazine rhodamine probe that we used to determine the reaction kinetics of various dienophiles in a fluorescence assay. Under proximity-driven conditions the reaction was found to be several orders of magnitude faster, and we observed almost no background reaction when proximity was not induced. This fundamental study identifies a minimally sized fluorogenic tetrazine dienophile reactant pair that has potential to be generally used for the visualization of biomolecular interactions with temporal and spatial resolution in living systems.
N-heterocyclic moieties are abundant among pharmaceuticals and agrochemicals, but a challenge for metalorganic and organocatalytic transformations. We present tripeptides of the type H-Pro-Pro-Xaa as catalysts for stereoselective conjugate addition reactions between N-heterocyclic substituted aldehydes and electrophiles. Alkyl substituents at the N-terminal proline, the reactive site, were crucial for high chemo-and stereoselectivity. Different N-heterocyclic moieties, even at both reaction partners, were readily tolerated and products were obtained in yields of 61-95% and enantioselectivities of up to 98% ee.
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