Experimental and Computational Mechanistic Study of Carbonazidate-Initiated Cascade Reactions.

A variety of Huisgen cyclization or nitrene/carbene alkyne cascade reactions with different types of termination were investigated. Accessible nitrene precursors were assessed, and carbonazidates were found to be the only effective initiators. Solvents, terminal alkynyl substituents, and catalysts can all impact the reaction outcome.

Synthesis and Application of Constrained Amidoboronic Acids Using Amphoteric Boron-Containing Building Blocks.

Amidoboronic acid-containing peptidomimetics are an important class of scaffolds in chemistry and drug discovery. Despite increasing interest in boron-based enzyme inhibitors, constrained amidoboronic acids have received little attention due to the limited options available for their synthesis. We describe a new methodology to prepare both α- and β-amidoboronic acids that impose restrictions on backbone angles.

Structure and Computational Basis for Backbone Rearrangement in Marine Oxasqualenoids.

Six novel oxasqualenoids (polyether triterpenes) were isolated from the red alga . Laurokanols A-E (-) comprise an unreported tricyclic core with a [6,6]-spiroketal system. Yucatecone () shows a biogenetically intriguing epimerization at C14.

1-BENZYLSPIRO[PIPERIDINE-4,1'-PYRIDO[3,4-b]indole] 'co-potentiators' for minimal function CFTR mutants.

We previously identified a spiro [piperidine-4,1-pyrido [3,4-b]indole] class of co-potentiators that function in synergy with existing CFTR potentiators such as VX-770 or GLGP1837 to restore channel activity of a defined subset of minimal function cystic fibrosis transmembrane conductance regulator (CFTR) mutants. Here, structure-activity studies were conducted to improve their potency over the previously identified compound, 20 (originally termed CP-A01). Targeted synthesis of 37 spiro [piperidine-4,1-pyrido [3,4-b]indoles] was generally accomplished using versatile two or three step reaction protocols with each step having high efficiency.

Tipping the balance: theoretical interrogation of divergent extended heterolytic fragmentations.

Herein we interrogate a type of heterolytic fragmentation reaction called a 'divergent fragmentation' using density functional theory (DFT), natural bond orbital (NBO) analysis, molecular dynamics (AIMD), and external electric field (EEF) calculations. We demonstrate that substituents, electrostatic environment and non-statistical dynamic effects all influence product selectivity in reactions that involve divergent fragmentation pathways. Direct dynamics simulations reveal an unexpected post-transition state bifurcation (PTSB), and EEF calculations suggest that some transition states for divergent pathways can, in principle, be selectively stabilized if an electric field of the correct magnitude is oriented appropriately.

Reconsidering the Structure of Serlyticin-A.

Serlyticin-A is a secondary metabolite first isolated from a culture of grown using squid pen as the sole carbon/nitrogen source. A previous study by Kuo et al. demonstrated that it has antioxidative and antiproliferative properties.

Davis-Beirut Reaction: A Photochemical Brønsted Acid Catalyzed Route to -Aryl 2-Indazoles.

The Davis-Beirut reaction provides access to 2-indazoles from aromatic nitro compounds. However, -aryl targets have been traditionally challenging to access due to competitive alternate reaction pathways. Previously, the key nitroso imine intermediate was generated under alkaline conditions, but as reported here, the photochemistry of -nitrobenzyl alcohols empowered Brønsted acid catalyzed conditions for accessing -aryl targets.

Accessing Multiple Classes of 2 H-Indazoles: Mechanistic Implications for the Cadogan and Davis-Beirut Reactions.

The Cadogan cyclization is a robust but harsh method for the synthesis of 2 H-indazoles, a valuable class of nitrogen heterocycles. Although nitrene generation by exhaustive deoxygenation is widely accepted as the operating mechanism in the reductive cyclization of nitroaromatics, non-nitrene pathways have only been theorized previously. Here, 2 H-indazole N-oxides were synthesized through an interrupted Cadogan/Davis-Beirut reaction and are presented as direct evidence of competent oxygenated intermediates; mechanistic implications for both reactions are discussed.