A HMPA-H2O mediated oxygenative carbocyclization of 2-alkynylphenyl-substituted p-quinone methides to indenones.

Herein, we report a transition-metal and base-free protocol to access a wide range of functionalized indenone derivatives through a HMPA-H2O-mediated oxygenative annulation of 2-alkynylphenyl-substituted p-quinone methides. This method worked effectively for most of the p-QMs investigated and the corresponding indenone derivatives were obtained in moderate to good yields. This methodology was further extended to the formal synthesis of one of the resveratrol based natural products, (±)-isopaucifloral F.

Bis(amino)cyclopropenium Ion as a Hydrogen-Bond Donor Catalyst for 1,6-Conjugate Addition Reactions.

The catalytic application of the bis(amino)cyclopropenium ion has been investigated in conjugate addition reactions. The hydrogen atom, which is attached to the cyclopropene ring of bis(amino)cyclopropenium salts, is moderately acidic and can potentially serve as a hydrogen-bond donor catalyst in some organic transformations. This hypothesis has been successfully realized in the 1,6-conjugate addition reactions of p-quinone methides with various nucleophiles such as indole, 2-naphthol, thiols, phenols, and so forth. The spectroscopic studies (NMR and UV-vis) as well as the deuterium isotope labeling studies clearly revealed that the hydrogen atom (C-H) that is present in the cyclopropene ring of the catalyst is indeed solely responsible for catalyzing these transformations. In addition, these studies also strongly indicate that the C-H hydrogen of the cyclopropene ring activates the carbonyl group of the p-quinone methide through hydrogen bonding.

Recent advances in the organocatalytic applications of cyclopropene- and cyclopropenium-based small molecules.

The development of novel small molecule-based catalysts for organic transformations has increased noticeably in the last two decades. A very recent addition to this particular research area is cyclopropene- and cyclopropenium-based catalysts. At one point in time, particularly in the mid-20th century, much attention was focused on the structural aspects and physical properties of cyclopropene-based compounds. However, a paradigm shift was observed in the late 20th century, and the focus shifted to the synthetic utility of these compounds. In fact, a wide range of cyclopropene derivatives have been found serving as valuable synthons for the construction of carbocycles, heterocycles and other useful organic compounds. In the last few years, the catalytic applications of cyclopropene/cyclopropenium-based compounds have been uncovered and many synthetic protocols have been developed using cyclopropene-based compounds as organocatalysts. Therefore, the main objective of this review is to highlight recent developments in the catalytic applications of cyclopropene-based small molecules in different areas of organocatalysis such as phase-transfer catalysis (PTC), Brønsted base catalysis, hydrogen-bond donor catalysis, nucleophilic carbene catalysis, and electrophotocatalysis developed within the past two decades.

Pd(II)-catalyzed annulation of terminal alkynes with 2-pyridinyl-substituted p-quinone methides: direct access to indolizines.

A Pd-catalyzed direct method has been developed to access 1,3-disubstituted indolizines. This reaction proceeds through a regiospecific annulation of terminal alkynes with 2-pyridinyl-substituted p-quinone methides and, in most of the cases, the desired 1,3-disubstituted indolizines were obtained in moderate to good isolated yields. The control experiments suggested that the reaction does proceed through a substrate-controlled regiospecific formal [3 + 2]-annulation pathway.

Deciphering the Role of Intramolecular Networking in Cholic Acid-Peptide Conjugates on the Lipopolysaccharide Surface in Combating Gram-Negative Bacterial Infections.

The presence of lipopolysaccharide and emergence of drug resistance make the treatment of Gram-negative bacterial infections highly challenging. Herein, we present the synthesis and antibacterial activities of cholic acid-peptide conjugates (CAPs), demonstrating that valine-glycine dipeptide-derived CAP 3 is the most effective antimicrobial. Molecular dynamics simulations and structural analysis revealed that a precise intramolecular network of CAP 3 is maintained in the form of evolving edges, suggesting intramolecular connectivity. Further, we found high conformational rigidity in CAP 3 that confers maximum perturbations in bacterial membranes relative to other small molecules. Interestingly, CAP 3-coated catheters did not allow the formation of biofilms in mice, and treatment of wound infections with CAP 3 was able to clear the bacterial infection. Our results demonstrate that molecular conformation and internal connectivity are critical parameters to describe the antimicrobial nature of compounds, and the analysis presented here may serve as a general principle for the design of future antimicrobials.