Quaternary carbons are useful motifs in chemical synthesis but can be challenging to prepare using many chemical methods. Here, we report a stereoselective synthesis of -quaternary lactams using flavin-dependent 'ene'-reductases via a 5-exo-trig radical cyclization. The products are formed in moderate to good levels of enantioselectivity using an 'ene'-reductase variant from . This method highlights the opportunity for biocatalysis to form quaternary centers using non-natural reactions.

We herein report the synthesis and biophysical evaluation of triazolyl dibenzo[]phenazine derivatives as a novel class of G-quadruplex ligands. The aromatic core facilitates π-π interaction and the flexible, protonatable side chains interact with the phosphate backbone of DNA electrostatic interactions. Förster resonance energy transfer (FRET) melting assay and isothermal titration calorimetry (ITC) studies suggest that these ligands show binding preference for the G-quadruplex over G-quadruplexes found in the promoter region of various oncogenes and duplex DNA. The telomeric repeat amplification protocol (Q-TRAP) assay reveals that these ligands reduce telomerase activity in cancer cells.

This Minireview provides insight into the early history of nucleophilic phosphinocatalysis. The concepts of 1,4-addition of a tertiary phosphine to an α,β-enone and of equilibrium between the resulting phosphonium zwitterion and phosphonium ylide established a fundamental basis for the development of several classical transformations, including the Rauhut-Currier, Morita, McClure-Baizer-Anderson, and Oda reactions.

Cycloaddition reactions can be used to efficiently assemble pyrrolidine rings that are significant in a variety of chemical and biological applications. We have developed a method for the formal cycloaddition of cyclopropyl ketones with hydrazones that utlizes photoredox catalysis to enable the synthesis of a range of structurally diverse pyrrolidine rings. The key insight enabling the scope of photoredox [3+2] cycloadditions to be expanded to C=N electrophiles was the use of a redox auxiliary strategy that allowed for photoreductive activation of the cyclopropyl ketone without the need for an exogenous tertiary amine co-reductant. These conditions prevent the deleterious reductive ring-opening of the cyclopropyl substrates, enabling a range of less-reactive coupling partners to participate in this cycloaddition.

Because of their pivotal biological functions, attention to sugars and glycobiology has grown rapidly in recent decades, leading to increased demand for homogeneous oligosaccharides. The stereoselective preparation of oligosaccharides by chemical means remains challenging and continues to be a vivid research area for organic chemists. In the past decade, new approaches and reinvestigated traditional methods have transformed the field. These developments include novel catalyses, various types of glycosylation modulators and the use of photochemical energy to facilitate glycosylation. This Minireview presents a brief overview of the latest trends in chemical glycosylation, with emphasis on the stereoselective synthetic protocols developed in the past decade.

We have developed a conceptually new generation of non-peptidic HIV-1 protease inhibitors incorporating novel structural templates inspired by nature. This has resulted in protease inhibitors with exceptional potency and excellent pharmacological and drug-resistance profiles. The design of a stereochemically defined -tetrahydrofuran (-THF) scaffold followed by modifications to promote hydrogen bonding interactions with the backbone atoms of HIV-1 protease led to darunavir, the first clinically approved drug for treatment of drug resistant HIV. Subsequent X-ray crystal structure-based design efforts led us to create a range of exceptionally potent inhibitors incorporating other intriguing molecular templates possessing fused ring polycyclic ethers with multiple stereocenters. These structural templates are critical to inhibitors' exceptional potency and drug-like properties. Herein, we will highlight the synthetic strategies that provided access to these complex scaffolds in a stereoselective and optically active form, enabling our medicinal chemistry and drug development efforts.

A straightforward phosphine-catalyzed formal [4+2] annulation between α-branched allenoates and arylidene azlactones has been developed to access highly functionalized spirocyclohexenes. This cyclization favors the γ-addition of the phosphine-activated allenoates over a β'-addition pathway. Detailed computational studies support the proposed mechanism and provide a reasonable explanation for the observed regioselectivity and the noted effect of the catalyst.

The use of readily accessible ammonium ylides for (asymmetric) transformations, especially cyclization reactions, has received considerable attention over the past two decades. A variety of highly enantioselective protocols to facilitate annulation reactions have recently been introduced as an alternative to other common methods including S-ylide-mediated strategies. It is the intention of this short review to provide an introduction to this field by highlighting the potential of ammonium ylides for (asymmetric) cyclization reactions as well as to present the limitations and challenges of these methods.

A TiCl-mediated reaction for the direct amination of α-hydroxy amides has been developed. This simple, general, additive/base/ligand-free reaction is mediated by economical TiCl. The reaction runs under mild conditions. This highly efficient C-N bond formation protocol is valid for diverse amines, including primary, secondary and heterocyclic amines, and even a primary amide and indole.

2-Nitrobenzyl isocyanide is reported as a universal convertible isocyanide with extensive applicability in both Ugi four-component reaction (Ugi-4CR) and Ugi-tetrazole reaction. The cleavage of this isocyanide from 17 examples in both acidic and basic conditions is presented. Additionally, this isocyanide has various handling and synthetic advantages, as it is easy to prepare, odorless, stable, and easy to handle as a solid.

This review summarizes recent developments in palladium-catalyzed alkene carboalkoxylation and carboamination reactions. New synthetic methods that have been reported in the past four years are described, along with mechanistic issues and the influence of mechanism on product stereochemistry. The applications of these transformations to the synthesis of natural products and other biologically relevant compounds are also discussed.

The synthesis of enantioenriched small molecules is an ongoing goal of organic chemists. This focus review explores the use of kinetic resolutions catalyzed by chiral Brønsted acids. Methods include classic kinetic resolutions and dynamic kinetic resolutions. The small molecules obtained are potentially valuable intermediates in the synthesis of biologically important compounds.

Phosphinocatalysis provides a new approach toward 3-substituted-4-quinolones. A simple procedure, which uses PhP as an inexpensive catalyst and -phenyl 2-(-tosylamido)benzothioates and activated alkynes as starting materials, provides direct access to several 3-aroyl-4-quinolones and methyl 4-quinolone-3-carboxylate esters. The reaction presumably occurs through general base catalysis, with the initial addition of PhP to the activated alkyne generating the phosphonium enoate zwitterion, which acts as the strong base that initiates the reaction.

A concise enantioselective synthesis of (-)-paroxetine () and (-)-femoxetine has been achieved. Key to these syntheses is a -heterocyclic carbene catalyzed homoenolate addition to a nitroalkene followed by in situ reduction of the nitro-group to rapidly access δ-lactams.

: The synthesis of linderaspirone A has been accomplished in only three steps by a Darzens cyclopentenedione synthesis and dioxygen-assisted photochemical dimerization. Moreover, the thermal isomerization of linderaspirone A into bi-linderone has been discovered, which may give clues to the biosynthetic pathway for bi-linderone.