Chemical Synthesis and Biological Application of Modified Oligonucleotides.

RNA plays a myriad of roles in the body including the coding, decoding, regulation, and expression of genes. RNA oligonucleotides have garnered significant interest as therapeutics via antisense oligonucleotides or small interfering RNA strategies for the treatment of diseases ranging from hyperlipidemia, HCV, and others. Additionally, the recently developed CRISPR-Cas9 mediated gene editing strategy also relies on Cas9-associated RNA strands.

Rhodium-Catalyzed (5 + 2) and (5 + 1) Cycloadditions Using 1,4-Enynes as Five-Carbon Building Blocks.

Cycloaddition reactions are a hallmark in organic synthesis because they provide an efficient way to construct highly substituted carbo- and heterocycles found in natural products and pharmaceutical agents. Most cycloadditions occur under thermal or photochemical conditions, but transition-metal complexes can promote reactions that occur beyond these circumstances. Transition-metal complexation with alkynes, alkenes, allenes, or dienes often alters the reactivity of those π-systems and facilitates access to diverse cycloaddition products.

S-Adamantyl Group Directed Site-Selective Acylation: Applications in Streamlined Assembly of Oligosaccharides.

The site-selective functionalization of carbohydrates is an active area of research. Reported here is the surprising observation that the sterically encumbered adamantyl group directed site-selective acylation at the C2 position of S-glycosides through dispersion interactions between the adamantyl C-H bonds and the π system of the cationic acylated catalyst, which may have broad implications in many other chemical reactions. Because of their stability, chemical orthogonality, and ease of activation for glycosylation, the site-selective acylation of S-glycosides streamlines oligosaccharide synthesis and will have wide applications in complex carbohydrate synthesis.

Intermolecular Regio- and Stereoselective Hetero-[5+2] Cycloaddition of Oxidopyrylium Ylides and Cyclic Imines.

We have developed the first intermolecular hetero-[5+2] cycloaddition reaction between oxidopyrylium ylides and cyclic imines with excellent control of regio- and stereoselectivity. Surprisingly, divergent stereochemistry was observed depending on the substitution pattern of the oxidopyrylium ylide. This new reaction provides quick access to highly substituted nitrogen-containing seven-membered rings-azepanes.

Catalytic Site-Selective Acylation of Carbohydrates Directed by Cation-n Interaction.

Site-selective functionalization of hydroxyl groups in carbohydrates is one of the long-standing challenges in chemistry. Using a pair of chiral catalysts, we now can differentiate the most prevalent trans-1,2-diols in pyranoses systematically and predictably. Density functional theory (DFT) calculations indicate that the key determining factor for the selectivity is the presence or absence of a cation-n interaction between the cation in the acylated catalyst and an appropriate lone pair in the substrate.

Synthesis of Carbazoles and Carbazole-Containing Heterocycles via Rhodium-Catalyzed Tandem Carbonylative Benzannulations.

Polycyclic aromatic compounds are important constituents of pharmaceuticals and other materials. We have developed a series of Rh-catalyzed tandem carbonylative benzannulations for the synthesis of tri-, tetra-, and pentacyclic heterocycles from different types of aryl propargylic alcohols. These tandem reactions provide efficient access to highly substituted carbazoles, furocarbazoles, pyrrolocarbazoles, thiophenocarbazoles, and indolocarbazoles.

Chiral Catalyst-Directed Dynamic Kinetic Diastereoselective Acylation of Lactols for De Novo Synthesis of Carbohydrate.

The control of the stereochemistry at the anomeric position is still one of the major challenges of synthetic carbohydrate chemistry. We have developed a new strategy consisting of a chiral catalyst-directed acylation followed by a palladium-catalyzed glycosidation to achieve high α- and β-stereoselectivity on the anomeric position. The former process involves a dynamic kinetic diastereoselective acylation of lactols derived from Achmatowicz rearrangement, while the latter is a stereospecific palladium-catalyzed allylic alkylation.