One-Pot Synthesis of Cereblon Proteolysis Targeting Chimeras via Photoinduced C(sp)-C(sp) Cross Coupling and Amide Formation for Proteolysis Targeting Chimera Library Synthesis.

In this study, a one-pot synthesis via photoinduced C(sp)-C(sp) coupling followed by amide formation to access proteolysis targeting chimeras (PROTACs) was developed. The described protocol was studied on cereblon (CRBN)-based E3-ligase binders and (+)-JQ-1, a bromodomain inhibitor, to generate BET (bromodomain and extra terminal domain) targeting protein degraders. The generated PROTACs were profiled in vitro and tested for their degradation ability with several potent candidates identified.

Sesquiterpene Lactones from : Structural Characterization and Biological Evaluation.

The genus is an extremely rich source of biologically active sesquiterpene lactones. The present report describes the spectroscopic structure elucidation and the cytotoxic and antimicrobial properties of five hitherto unknown germacranolide-like sesquiterpenoids and several known compounds. These new derivatives include a compound () with an unprecedented 10/5/5/6 tetracyclic framework featuring a hexahydro-1,3,7-furo[3',4':3,4]furo[3,2-]pyridin-1-one core resulting from an intramolecular cyclization cascade involving a methacrylate substituent and a low molecular weight amine.

A practical and sustainable two-component Minisci alkylation photo-induced EDA-complex activation.

An operationally simple, open-air, and efficient light-mediated Minisci C-H alkylation method is described, based on the formation of an electron donor-acceptor (EDA) complex between nitrogen-containing heterocycles and redox-active esters. In contrast to previously reported protocols, this method does not require a photocatalyst, an external single electron transfer agent, or an oxidant additive. Achieved under mildly acidic and open-air conditions, the reaction incorporates primary-, secondary-, and tertiary radicals, including bicyclo[1.

Photochemical C-H arylation of heteroarenes for DNA-encoded library synthesis.

DNA-encoded library (DEL) technology has emerged as a time- and cost-efficient technique for the identification of therapeutic candidates in the pharmaceutical industry. Although several reaction classes have been successfully validated in DEL environments, there remains a paucity of DNA-compatible reactions that harness building blocks (BBs) from readily available substructures bearing multifunctional handles for further library diversification under mild, dilute, and aqueous conditions. In this study, the direct C-H carbofunctionalization of medicinally-relevant heteroarenes can be accomplished the photoreduction of DNA-conjugated (hetero)aryl halides to deliver reactive aryl radical intermediates in a regulated fashion within minutes of blue light illumination.

Photoredox-mediated hydroalkylation and hydroarylation of functionalized olefins for DNA-encoded library synthesis.

DNA-encoded library (DEL) technology features a time- and cost-effective interrogation format for the discovery of therapeutic candidates in the pharmaceutical industry. To develop DEL platforms, the implementation of water-compatible transformations that facilitate the incorporation of multifunctional building blocks (BBs) with high C(sp) carbon counts is integral for success. In this report, a decarboxylative-based hydro of DNA-conjugated trifluoromethyl-substituted alkenes enabled by single-electron transfer (SET) and subsequent hydrogen atom termination through electron donor-acceptor (EDA) complex activation is detailed.

Multivalency Beats Complexity: A Study on the Cell Uptake of Carbohydrate Functionalized Nanocarriers to Dendritic Cells.

Herein, we report the synthesis of carbohydrate and glycodendron structures for dendritic cell targeting, which were subsequently bound to hydroxyethyl starch (HES) nanocapsules prepared by the inverse miniemulsion technique. The uptake of the carbohydrate-functionalized HES nanocapsules into immature human dendritic cells (hDCs) revealed a strong dependence on the used carbohydrate. A multivalent mannose-terminated dendron was found to be far superior in uptake compared to the structurally more complex oligosaccharides used.

Total Synthesis of a Partial Structure from Arabinogalactan and Its Application for Allergy Prevention.

Arabinogalactan, a microheterogeneous polysaccharide occurring in plants, is known for its allergy-protective activity, which could potentially be used for preventive allergy treatment. New treatment options are highly desirable, especially in a preventive manner, due to the constant rise of atopic diseases worldwide. The structural origin of the allergy-protective activity of arabinogalactan is, however, still unclear and isolation of the polysaccharide is not feasible for pharmaceutical applications due to a variation of the activity of the natural product and contaminations with endotoxins.

-clerodane diterpenoids from Sch.Bip. ex A.Rich.

Two hitherto unknown -clerodane-type diterpenoids along with twelve known compounds have been isolated from Sch.Bip. ex A.

HPMA-Based Nanocarriers for Effective Immune System Stimulation.

The selective activation of the immune system using nanoparticles as a drug delivery system is a promising field in cancer therapy. Block copolymers from HPMA and laurylmethacrylate-co-hymecromone-methacrylate allow the preparation of multifunctionalized core-crosslinked micelles of variable size. To activate dendritic cells (DCs) as antigen presenting cells, the carbohydrates mannose and trimannose are introduced into the hydrophilic corona as DC targeting units.

Bioconjugation of Small Molecules to RNA Impedes Its Recognition by Toll-Like Receptor 7.

A fundamental mechanism of the innate immune system is the recognition, extra- and intracellular pattern-recognition receptors, of pathogen-associated molecular patterns. A prominent example is represented by foreign nucleic acids, triggering the activation of several signaling pathways. Among these, the endosomal toll-like receptor 7 (TLR7) is known to be activated by single-stranded RNA (ssRNA), which can be specifically influenced through elements of sequence structure and posttranscriptional modifications.