The Diels-Alder reaction is a cornerstone of modern organic synthesis. Despite this, it remains essentially inaccessible to biosynthetic approaches. Only a few natural enzymes catalyze even a formal [4 + 2] cycloaddition, and it remains uncertain if any of them proceed via the Diels-Alder mechanism. In this study, we focus on the [4 + 2] cycloaddition step in the biosynthesis of spinosyn A, a reaction catalyzed by SpnF enzyme, one of the most promising "true Diels-Alderase" candidates. The four currently proposed mechanisms (including the Diels-Alder one) for this reaction in water (as a first-order approximation of the enzymatic reaction) are evaluated by an exhaustive quantum mechanical search for possible transition states (728 were found in total). We find that the line between the recently proposed bis-pericyclic [J. Am. Chem. Soc. 2016, 138 (11), 3631] and Diels-Alder routes is blurred, and favorable transition states of both types may coexist. Application of the Curtin-Hammett principle, however, reveals that the bis-pericyclic mechanism accounts for ∼83% of the reaction flow in water, while the classical Diels-Alder mechanism contributes only ∼17%. The current findings provide a route for modeling this reaction inside the SpnF active site and inferring the catalytic architecture of possible Diels-Alderases.

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The review summarizes the publications, available at the time it was written, addressing the chemical and biological processes that occur in the human body upon exposure to coronaviruses, in particular SARS-CoV-2. The mechanisms of viral particle entry into the cell, viral replication and impact on the immune system and on oxygen transport system are considered. The causes behind complications of the viral infection, such as vasculitis, thrombosis, cytokine storm and lung fibrosis, are discussed. The latest research in the field of small molecule medications to counteract the virus is surveyed. Molecular targets and possible vectors to exploit them are considered. The review is primarily written for specialists who want to understand the chains of activation, replication, action and inhibition of SARS-CoV-2. Due to the short period of such studies, the data on complexes of small molecule compounds with possible protein targets are not numerous, but they will be useful in the search and synthesis of new potentially effective drugs. The bibliography includes 144 references.

We compared explicit and implicit solvation approaches in modeling the free energy profile of the final step of Suzuki-Miyaura coupling. Both approaches produced similar ΔG(≠) in all the studied solvents (benzene, toluene, DMF, ethanol, and water). Solvation free energies of individual reaction components reasonably correlated for explicit and implicit models in aprotic solvents (RMSE = 30-50 kJ mol(-1), R(2) > 0.71). However for ethanol and water the correlation was poor. We attributed this difference to the formation of the PdH-O hydrogen bond with Pd(PPh3)2 which was surprisingly observed in explicit modeling. Further QM calculations of the Pd(PPh3)2-H2O system confirmed the direction (PdH) and stability of this bonding. Therefore we stress the need for considering explicit solvation for modeling Pd-catalyzed reactions in protic solvents.