Targeting ferroptosis with the lipoxygenase inhibitor PTC-041 as a therapeutic strategy for the treatment of Parkinson's disease.

Parkinson's disease is the second most common neurodegenerative disorder, affecting nearly 10 million people worldwide. Ferroptosis, a recently identified form of regulated cell death characterized by 15-lipoxygenase-mediated hydroperoxidation of membrane lipids, has been implicated in neurodegenerative disorders including amyotrophic lateral sclerosis and Parkinson's disease. Pharmacological inhibition of 15 -lipoxygenase to prevent iron- and lipid peroxidation-associated ferroptotic cell death is a rational strategy for the treatment of Parkinson's disease.

Acyl Glycosides through Stereospecific Glycosyl Cross-Coupling: Rapid Access to C(sp)-Linked Glycomimetics.

Replacement of a glycosidic bond with hydrolytically stable C-C surrogates is an efficient strategy to access glycomimetics with improved physicochemical and pharmacological properties. We describe here a stereoretentive cross-coupling reaction of glycosyl stannanes with C(sp)- and C(sp)-thio(seleno)esters suitable for the preparation -acyl glycosides as synthetic building blocks to obtain C(sp)-linked and fluorinated glycomimetics. First, we identified a set of standardized conditions employing a Pd(0) precatalyst, CuCl additive, and phosphite ligand that provided access to -acyl glycosides without deterioration of anomeric integrity and decarbonylation of the acyl donors (>40 examples).

Rethinking Carbohydrate Synthesis: Stereoretentive Reactions of Anomeric Stannanes.

In this Concept article, recent advances are highlighted in the synthesis and applications of anomeric nucleophiles, a class of carbohydrates in which the C1 carbon bears a carbon-metal bond. First, the advantages of exploiting the carboanionic reactivity of carbohydrates and the methods for the synthesis of mono- and oligosaccharide stannanes are discussed. Second, recent developments in the glycosyl cross-coupling method resulting in the transfer of anomeric configuration from C1 stannanes to C-aryl glycosides are reviewed.

Direct Dehydrative Glycosylation of C1-Alcohols.

Due to the central role played by carbohydrates in a multitude of biological processes, there has been a sustained interest in developing effective glycosylation methods to enable more thorough investigation of their essential functions. Among the myriad technologies available for stereoselective glycoside bond formation, dehydrative glycosylation possesses a distinct advantage given the unique properties of C1-alcohols such as straightforward preparation, stability, and a general reactivity compatible with a diverse set of reaction conditions. In this Focus Review, a survey of direct dehydrative glycosylations of C1-alcohols is provided with an emphasis on recent achievements, pervading limitations, mechanistic insights, and applications in total synthesis.

Stereoretentive Reactions at the Anomeric Position: Synthesis of Selenoglycosides.

Reported is the stereospecific cross-coupling of anomeric stannanes with symmetrical diselenides, resulting in the synthesis of selenoglycosides with exclusive anomeric control. The reaction proceeds without the need for directing groups and is compatible with free hydroxy groups as demonstrated in the preparation of glycoconjugates derived from mono-, di-, and trisaccharides and peptides (35 examples). Given its generality and broad substrate scope, the glycosyl cross-coupling method presented herein can find use in the synthesis of selenium-containing glycomimetics and glycoconjugates.

Constrained saccharides: a review of structure, biology, and synthesis.

Review primarily covers from 1995-2018Carbohydrate function, recognized in a multitude of biological processes, provides a precedent for developing carbohydrate surrogates that mimic the structure and function of bioactive compounds. In order to constrain highly flexible oligosaccharides, synthetic tethering techniques like those exemplified by stapled peptides are utilized to varying degrees of success. Naturally occurring constrained carbohydrates, however, exist with noteworthy cytotoxic and chemosensitizing properties.

Glycosyl Cross-Coupling of Anomeric Nucleophiles: Scope, Mechanism, and Applications in the Synthesis of Aryl C-Glycosides.

Stereoselective manipulations at the C1 anomeric position of saccharides are one of the central goals of preparative carbohydrate chemistry. Historically, the majority of reactions forming a bond with anomeric carbon has focused on reactions of nucleophiles with saccharide donors equipped with a leaving group. Here, we describe a novel approach to stereoselective synthesis of C-aryl glycosides capitalizing on the highly stereospecific reaction of anomeric nucleophiles.