Development of a Crystallization-Induced Diastereomer Transformation of Oxime Isomers for the Asymmetric Synthesis of (1,6)-3,9-Diazabicyclo[4.2.1]nonane.

Herein we report a practical crystallization-induced diastereomer transformation (CIDT) of oxime isomers for the scalable asymmetric synthesis of the bicyclic diamine (1,6)-3,9-diazabicyclo[4.2.1]nonane derivative that serves as a valuable building block in medicinal chemistry.

Highly Selective Hydrogenation of C═C Bonds Catalyzed by a Rhodium Hydride.

Under mild conditions (room temperature, 80 psi of H) Cp*Rh(2-(2-pyridyl)phenyl)H catalyzes the selective hydrogenation of the C═C bond in α,β-unsaturated carbonyl compounds, including natural product precursors with bulky substituents in the β position and substrates possessing an array of additional functional groups. It also catalyzes the hydrogenation of many isolated double bonds. Mechanistic studies reveal that no radical intermediates are involved, and the catalyst appears to be homogeneous, thereby affording important complementarity to existing protocols for similar hydrogenation processes.

The Development of Reaction Cascades to Synthesize Dimeric Coccinellid Alkaloids.

Over the course of the past decade, our group has been intensely interested in achieving the laboratory synthesis of varied members of the coccinellid alkaloid family of natural products. These compounds, produced by varied species of ladybugs throughout the world as defensive agents, include several polycyclic members that can formally be considered as either monomeric or dimeric with architectures that contain between 3 and 7 ring systems along with an array of stereocenters. As a result of their fascinating structures, many groups have achieved syntheses of varied monomeric members using a variety of synthetic strategies and tactics.

Structure of papain-like protease from SARS-CoV-2 and its complexes with non-covalent inhibitors.

The pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to expand. Papain-like protease (PLpro) is one of two SARS-CoV-2 proteases potentially targetable with antivirals. PLpro is an attractive target because it plays an essential role in cleavage and maturation of viral polyproteins, assembly of the replicase-transcriptase complex, and disruption of host responses.

A Concise, Enantiospecific Total Synthesis of Chilocorine C Fueled by a Reductive Cyclization/Mannich Reaction Cascade.

Among defensive alkaloids isolated from ladybugs, the heterodimeric member chilocorine C possesses an alluring monomeric unit that combines quinolizidine and indolizidine substructures. Indeed, the overall stereochemical disposition of its ring fusions is distinct from those of related natural products. Herein we show that a carefully orchestrated sequence with several chemoselective transformations, including a designed cascade that accomplishes nine distinct chemical reactions in one-pot, can smoothly forge that domain and ultimately enable a 15-step, 11-pot enantiospecific synthesis of the natural product.

Mannich-type Reactions of Cyclic Nitrones: Effective Methods for the Enantioselective Synthesis of Piperidine-containing Alkaloids.

Even though there are dozens of biologically active 2-substituted and 2,6-disubstituted piperidines, only a limited number of approaches exist for their synthesis. Herein is described two Mannich-type additions to nitrones, one using β-ketoacids under catalyst-free conditions and another using methyl ketones in the presence of chiral thioureas, which can generate a broad array of such 2-substituted materials, as well as other ring variants, in the form of β-N-hydroxy-aminoketones. Both processes have broad scope, with the latter providing products with high enantioselectivity (up to 98 %).

(1,2-Diaminoethane-1,2-diyl)bis(N-methylpyridinium) Salts as a Prospective Platform for Designing Recyclable Prolinamide-Based Organocatalysts.

A new efficient and highly recyclable organocatalyst has been developed for asymmetric cross-aldol reactions under neat conditions in ketone-ketone, ketone-aldehyde, and aldehyde-aldehyde systems. The catalyst features two prolinamide fragments and a C2-symmetrical (1,2-diaminoethane-1,2-diyl)bis(N-methylpyridinium) group. The catalyst retained high activity and excellent stereoselection over the operating period of more than 830 h (25 cycles).