The Mitsunobu reaction plays a vital part in organic chemistry due to its wide synthetic applications. It is considered as a significant reaction for the interconversion of one functional group (alcohol) to another (ester) in the presence of oxidizing agents (azodicarboxylates) and reducing agents (phosphines). It is a renowned stereoselective reaction which inverts the stereochemical configuration of end products. One of the most important applications of the Mitsunobu reaction is its role in the synthesis of natural products. This review article will focus on the contribution of the Mitsunobu reaction towards the total synthesis of natural products, highlighting their biological potential during recent years.

The Petasis reaction, also called the Petasis Borono–Mannich reaction, is a multicomponent reaction that couples a carbonyl derivative, an amine and boronic acids to yield substituted amines. The reaction proceeds efficiently in the presence or absence of a specific catalyst and solvent. By employing this reaction, a diverse range of chiral derivatives can easily be obtained, including α-amino acids. A broad substrate scope, high yields, distinct functional group tolerance and the availability of diverse catalytic systems constitute key features of this reaction. In this review article, attention has been drawn toward the recently reported methodologies for executing the Petasis reaction to produce structurally simple to complex aryl/allyl amino scaffolds.

A novel series of substituted benzofuran-tethered triazolylcarbazoles was synthesized in good to high yields (65–89%) via S-alkylation of benzofuran-based triazoles with 2-bromo-N-(9-ethyl-9H-carbazol-3-yl)acetamide. The inhibitory potency of the synthesized compounds against SARS-CoV-2 was evaluated by enacting molecular docking against its three pivotal proteins, namely, M^pro (main protease; PDB ID: 6LU7), the spike glycoprotein (PDB ID: 6WPT), and RdRp (RNA-dependent RNA polymerase; PDB ID: 6M71). The docking results indicated strong binding affinities between SARS-CoV-2 proteins and the synthesized compounds, which were thereby expected to obstruct the function of SARS proteins. Among the synthesized derivatives, the compounds 9e, 9h, 9i, and 9j exposited the best binding scores of −8.77, −8.76, −8.87, and −8.85 Kcal/mol against M^pro, respectively, −6.69, −6.54, −6.44, and −6.56 Kcal/mol against the spike glycoprotein, respectively, and −7.61, −8.10, −8.01, and −7.54 Kcal/mol against RdRp, respectively. Furthermore, the binding scores of 9b (−8.83 Kcal/mol) and 9c (−8.92 Kcal/mol) against 6LU7 are worth mentioning. Regarding the spike glycoprotein, 9b, 9d, and 9f expressed high binding energies of −6.43, −6.38, and −6.41 Kcal/mol, accordingly. Correspondingly, the binding affinity of 9g (−7.62 Kcal/mol) against RdRp is also noteworthy. Furthermore, the potent compounds were also subjected to ADMET analysis to evaluate their pharmacokinetic properties, suggesting that the compounds 9e, 9h, 9i, and 9j exhibited comparable values. These potent compounds may be selected as inhibitory agents and provide a pertinent context for further investigations.