Expanding Glycomic Investigations through Thiol-Derivatized Glycans.

N-(2-thioethyl)-2-aminobenzamide (TEAB), a novel glycan auxiliary, was synthesized and its utility was evaluated. The auxiliary was conjugated to glycans by reductive amination with the water-stable reagent 2-picoline borane complex. Glycan products, which ranged from 1 to 7 linked hexoses, were all isolated in yields ranging from 60% to 90% after purification by reverse-phase chromatography.

Development of a multifunctional neoglycoside auxiliary for applications in glycomics research.

A novel, multifunctional, tetrazine-containing neoglycoside auxiliary has been synthesized in three steps and 28% overall yield. The oxyamine was conjugated with unprotected carbohydrates under aqueous conditions (pH = 4.7), with DMF as a cosolvent, to provide neoglycosides in yields ranging between 51% and 68%.

Asymmetric Synthesis of Stereogenic Phosphorus P(V) Centers Using Chiral Nucleophilic Catalysis.

Organophosphates have been widely used in agrochemistry, as reagents for organic synthesis, and in biochemistry. Phosphate mimics possessing four unique substituents, and thereby a chirality center, are useful in transition metal catalysis and as nucleotide therapeutics. The catalytic, stereocontrolled synthesis of phosphorus-stereogenic centers is challenging and traditionally depends on a resolution or use of stochiometric auxiliaries.

Transformation of aldehydes into nitriles in an aqueous medium using O-phenylhydroxylamine as the nitrogen source.

The conversion of an aldehyde into a nitrile can be efficiently performed using O-phenylhydroxylamine hydrochloride in buffered aqueous solutions. The reported method is specifically optimized for aqueous-soluble substrates including carbohydrates. Several reducing sugars including monosaccharides, disaccharides, and silyl-protected saccharides were transformed into cyanohydrins in high yields.

Synthesis, structure and photophysical properties of a 2D network with gold dicyanide donors coordinated to aza[5]helicene viologen acceptors.

A recently synthesized photoluminescent organic acceptor, 5,10-dimethyl-5,10-diaza[5]helicene is shown to react with dicyanoaurate anions to form a 2D network N,N-dimethylaza[5]helicene dicyanoaurate. The structure of the synthesized complex was investigated via X-ray crystallography showing the presence of [Au(CN)] dimers and monomers within the helicene framework. Photophysical measurements between 298 K and 10 K indicate quenching of the [Au(CN)] anion by 5,10-dimethyl-5,10-diaza[5]helicene via an electron transfer.

Structural analyses of NudT16-ADP-ribose complexes direct rational design of mutants with improved processing of poly(ADP-ribosyl)ated proteins.

ADP-ribosylation is a post-translational modification that occurs on chemically diverse amino acids, including aspartate, glutamate, lysine, arginine, serine and cysteine on proteins and is mediated by ADP-ribosyltransferases, including a subset commonly known as poly(ADP-ribose) polymerases. ADP-ribose can be conjugated to proteins singly as a monomer or in polymeric chains as poly(ADP-ribose). While ADP-ribosylation can be reversed by ADP-ribosylhydrolases, this protein modification can also be processed to phosphoribosylation by enzymes possessing phosphodiesterase activity, such as snake venom phosphodiesterase, mammalian ectonucleotide pyrophosphatase/phosphodiesterase 1, Escherichia coli RppH, Legionella pneumophila Sde and Homo sapiens NudT16 (HsNudT16).

Synthesis of dimeric ADP-ribose and its structure with human poly(ADP-ribose) glycohydrolase.

Poly(ADP-ribosyl)ation is a common post-translational modification that mediates a wide variety of cellular processes including DNA damage repair, chromatin regulation, transcription, and apoptosis. The difficulty associated with accessing poly(ADP-ribose) (PAR) in a homogeneous form has been an impediment to understanding the interactions of PAR with poly(ADP-ribose) glycohydrolase (PARG) and other binding proteins. Here we describe the chemical synthesis of the ADP-ribose dimer, and we use this compound to obtain the first human PARG substrate-enzyme cocrystal structure.

Stereospecific ring expansion of chiral vinyl aziridines.

In this report, it is demonstrated that chiral vinyl aziridines can be stereospecifically ring expanded. This synthetic approach allows controlled access to chiral 2,5-cis- or 2,5-trans-3-pyrroline products from starting materials with the appropriate aziridine geometry. Twenty three ring expansion examples, most of which feature a stereospecific cyclization, are presented.

An efficient oxidative dearomatization-radical cyclization approach to symmetrically substituted bicyclic guttiferone natural products.

Detailed in this communication is an efficient synthetic approach towards the guttiferone family of natural products. Oxidatively unraveling a para-quinone monoketal followed by consecutive 5-exo radical cyclizations provides the bicyclic core. An additional strength of this approach is a late stage asymmetric desymmetrization of an advanced symmetric intermediate.

Creative approaches towards the synthesis of 2,5-dihydro- furans, thiophenes, and pyrroles. One method does not fit all!

A single method is never sufficient, which is why there is a great need for developing many diverse and creative approaches towards every chemical substrate class. This statement is supported by the contents of this perspective in addition to providing the reader with a helpful synthetic roadmap for selecting a suitable method for the building blocks being discussed. Detailed in this review are eight different synthetic approaches that provide access to valuable 2,5-dihydro- furan, thiophene and pyrrole building blocks.

Lewis acid catalyzed [1,3]-sigmatropic rearrangement of vinyl aziridines.

This paper details the copper-catalyzed ring expansion of vinyl aziridines to 3-pyrrolines. Broad substrate scope (24 examples) using tosyl- and phthalimide-protected vinyl aziridine substrates is observed. Cu(hfacac)2 was determined to be superior to all other catalysts tested.