Transition metal-free decarboxylative olefination of carboxylic acid salts.

The cost-effective and efficient synthesis of alkenes is highly significant due to their extensive applications in both synthetic and polymer industries. A transition metal-free approach has been devised for the chemoselective olefination of carboxylic acid salts. This modular approach provides direct access to valuable electron-deficient styrenes in moderate to good yields. Detailed mechanistic studies suggest anionic decarboxylation is followed by halogen ion transfer. This halogen transfer leads to an umpolung of reactant electronics, allowing for a rate-limiting rebound elimination.

Toll-like receptor (TLR) agonists as a driving force behind next-generation vaccine adjuvants and cancer therapeutics.

Until recently, the development of new human adjuvants was held back by a poor understanding of their mechanisms of action. The field was revolutionized by the discovery of the toll-like receptors (TLRs), innate immune receptors that directly or indirectly are responsible for detecting pathogen-associated molecular patterns (PAMPs) and respond to them by activating innate and adaptive immune pathways. Hundreds of ligands targeting various TLRs have since been identified and characterized as vaccine adjuvants. This work has important implications not only for the development of vaccines against infectious diseases but also for immuno-therapies against cancer, allergy, Alzheimer's disease, drug addiction and other diseases. Each TLR has its own specific tissue localization and downstream gene signalling pathways, providing researchers the opportunity to precisely tailor adjuvants with specific immune effects. TLR agonists can be combined with other TLR or alternative adjuvants to create combination adjuvants with synergistic or modulatory effects. This review provides an introduction to the various classes of TLR adjuvants and their respective signalling pathways. It provides an overview of recent advancements in the TLR field in the past 2-3 years and discusses criteria for selecting specific TLR adjuvants based on considerations, such as disease mechanisms and correlates of protection, TLR immune biasing capabilities, route of administration, antigen compatibility, new vaccine technology platforms, and age- and species-specific effects.

Structure activity relationship in ß-carboline derived anti-malarial agents.

Malaria, even though an avoidable and treatable disease, can be fatal if ignored. Artemisinin Combination Therapy (ACT) and RTS, S/AS01 vaccine (Mosquirix™) are the only modest means available with humans to overcome malaria, a lethal affliction wreaking havoc across the globe. Employment of ACT is associated with problems such as 'Artemisinin Resistance' and the 'Hypnozoite conundrum' that hinder the complete eradication of malaria. In this view, the natural products specifically comprising ß-carboline scaffold have shown good antiplasmodial responses against different strains of malaria. Taking these observations forward, researchers have performed structure-activity relationship (SAR) studies around three different ß-carboline skeletons (tetrahydro ß-carbolines, dihydro ß-carbolines, ß-carbolines) to design new ß-carboline derived heterocyclic structures or modified naturally occurring derivatives. In addition, different approaches such as dimerization and linkage to other moieties have also been adopted to enhance the antimalarial activity. The present review describes a comprehensive SAR study encapsulating various natural and synthetic ß-carbolines to elaborate upon the utility of these skeletons in designing drugs to subdue this deadly disease.

Yb(OTf)3-Catalyzed and Di-tert-butyl Dicarbonate-Mediated Decarboxylative Etherification and Esterification Reactions.

Protecting group chemistry has invariably captured the fascination of chemists because of its extensive viability in chemical synthesis. The present report describes our pioneer work of applying ytterbium triflate as a catalyst, for the reaction of alcohols with di-tert-butyl dicarbonate (Boc2O) leading to the formation of tert-butyl ethers. There exists no recorded evidence for the use of Yb(OTf)3 as a catalyst for the protection of alcohols to tert-butyl ethers, despite its excellent utility in various reactions. Yb(OTf)3 has been used predominantly in the catalytic deprotection studies such as selective deprotection of tert-butyl esters to carboxylic acids as well as prenyl ethers to alcohols. This study involved the critical evaluation of solvent, time, and temperature that finally led to an efficient protocol for the formation of tert-butyl ethers. Yb(OTf)3 catalyzed the formation of tert-butyl ethers, notably reducing the reaction time, which is exemplified by the achievement of up to 92% conversion of alcohols to tert-butyl ethers within an hour. Additionally, the report demonstrates the utility of this synthetic protocol for the protection of carboxylic acids.