Chloroformate-mediated ring cleavage of indole alkaloids leads to re-engineered antiplasmodial agents.

Natural product ring distortion strategies have enabled rapid access to unique libraries of stereochemically complex compounds to explore new chemical space and increase our understanding of biological processes related to human disease. Herein is described the development of a ring-cleavage strategy using the indole alkaloids yohimbine, apovincamine, vinburnine, and reserpine that were reacted with a diversity of chloroformates paired with various alcohol/thiol nucleophiles to enable the rapid synthesis of 47 novel small molecules. Ring cleavage reactions of yohimbine and reserpine produced two diastereomeric products in moderate to excellent yields, whereas apovincamine and vinburnine produced a single diastereomeric product in significantly lower yields.

Design, synthesis and evaluation of halogenated phenazine antibacterial prodrugs targeting nitroreductase enzymes for activation.

It is of great importance to develop new strategies to combat antibiotic resistance. Our lab has discovered halogenated phenazine (HP) analogues that are highly active against multidrug-resistant bacterial pathogens. Here, we report the design, synthesis, and study of a new series of nitroarene-based HP prodrugs that leverage intracellular nitroreductase (NTR) enzymes for activation and subsequent release of active HP agents.

Pyrazine and Phenazine Heterocycles: Platforms for Total Synthesis and Drug Discovery.

There are numerous pyrazine and phenazine compounds that demonstrate biological activities relevant to the treatment of disease. In this review, we discuss pyrazine and phenazine agents that have shown potential therapeutic value, including several clinically used agents. In addition, we cover some basic science related to pyrazine and phenazine heterocycles, which possess interesting reactivity profiles that have been on display in numerous cases of innovative total synthesis approaches, synthetic methodologies, drug discovery efforts, and medicinal chemistry programs.

Scaled Synthesis of Polyamine-Modified Cellulose Nanocrystals from Bulk Cotton and Their Use for Capturing Volatile Organic Compounds.

We have previously demonstrated that cellulose nanocrystals modified with poly(ethylenimine) (PEI--CNC) are capable of capturing volatile organic compounds (VOCs) associated with malodors. In this manuscript, we describe our efforts to develop a scalable synthesis of these materials from bulk cotton. This work culminated in a reliable protocol for the synthesis of unmodified cellulose nanocrystals (CNCs) from bulk cotton on a 0.

Ring Distortion of Vincamine Leads to the Identification of Re-Engineered Antiplasmodial Agents.

There is a significant need for new agents to combat malaria, which resulted in ∼409,000 deaths globally in 2019. We utilized a ring distortion strategy to create complex and diverse compounds from vincamine with the goal of discovering molecules with re-engineered biological activities. We found compound () to target chloroquine-resistant Dd2 parasites (EC = 1.

Degradation of pesticides using amine-functionalized cellulose nanocrystals.

A series of amine-functionalized cellulose nanocrystal materials were successfully synthesized, characterized, and evaluated for the remediation of pesticide contaminants from organic and aqueous media. Their ability to degrade malathion in organic systems has been examined, resulting in up to 100% degradation of the compound into detectable lower molecular weight by-products. A poly(ethylenimine) cellulose nanocrystal (CNC-PEI) material was also capable of degrading aqueous solutions of malathion, deltamethrin, and permethrin with 100%, 95%, and 78% degradation, respectively.

Iodinated Polyesters with Enhanced X-ray Contrast Properties for Biomedical Imaging.

Synthetic materials exhibiting contrast imaging properties have become vital to the field of biomedical imaging. However, polymeric biomaterials are lacking imaging contrast properties for deep tissue imaging. This report details the synthesis and characterization of a suite of aryl-iodo monomers, which were used to prepare iodinated polyesters using a pre-functionalization approach.

One-Pot Absolute Stereochemical Identification of Alcohols via Guanidinium Sulfate Crystallization.

A novel technique for the absolute stereochemical determination of alcohols has been developed that uses crystallization of guanidinium salts of organosulfates. The simple one-pot, two-step process leverages facile formation of guandinium organosulfate single crystals for the straightforward determination of the absolute stereochemistry of enantiopure alcohols by means of X-ray crystallography. The strong hydrogen bonding network drives the stability of the crystal lattice and allows for a diverse range of organic alcohol substrates to be analyzed.

Recent Advances in Polyesters for Biomedical Imaging.

Several synthetic materials exhibiting contrast imaging properties have become vital to the field of biomedical imaging. Polymeric biomaterials and metals are commonly used imaging agents and can assist in the monitoring of therapy response, migration, degradation, changes in morphology, defects, and image-guided surgery. In comparison to metals, most bio and synthetic polymers lack inherent imaging properties.

Poly(amine) modified kaolinite clay for VOC capture.

Polyethylenimine (PEI) functionalized kaolinite clay was successfully prepared, characterized, and assessed for the remediation of volatile organic compounds (VOCs) comprising the aldehyde, carboxylic acid, and disulfide functional group classes. A gas chromatographic vapor capture assay evaluated the capability of unmodified and modified clay material to capture representative aldehyde, carboxylic acid, and disulfide VOCs in a laboratory setting. Unmodified kaolinite (Kao) clay was moderately or poorly effective at remediating these VOCs, while the poly(amine) functionalized Kao was capable of capturing VOCs in the vapor phase with reductions up to 100%.