Current Organic Chemistry - Volume 26, Issue 8, 2022

The existence of a seven-membered cyclic core in several natural products and biomolecules vitalized the research on its synthesis. [5+2] cycloaddition has become a promising strategy for the construction of seven-membered ring systems by the formation of carboncarbon bonds in a single step, with strong regioselectivity and stereoselectivity. This review mainly focuses on recent developments in the area of [5+2] cycloaddition since 2019. Total synthesis of natural products involving [5+2] cycloaddition as a key step leading to the heptacyclic core has also been discussed. Synthesis of fused and bridged ring systems via the reactions involving inter and intramolecular [5+2] cycloadditions like oxidopyrylium-mediated [5+2] cycloadditions, [5+2] cycloadditions of vinyl cyclopropanes (VCPs), vinyl phenols, etc. is explained in the review with the latest examples. This review provides a useful guide for researchers exploring this powerful strategy to create more elegant heptacycles in their future research.

Deep eutectic solvents (DESs), also referred to as low transition temperature mixtures (LTTMs), have emerged as sustainable and cheap alternatives to conventional organic solvents in organic synthesis. This is attributed to their exceptional characteristics viz. easy preparation with readily available cheap materials, water compatibility, non-flammability, non-toxicity, biocompatibility, biodegradability, etc. All these properties label them as versatile and cost-effective green solvents. The first reported DES, choline chloride urea mixture has appeared as an innocuous solvent and catalyst in many organic transformations. This prospective DES combination has been applied extensively to the synthesis of a wide range of heterocyclic compounds including quinolones, spirooxindoles, etc. The conditions employed are relatively mild and do not require additional acid catalysts or organic solvents. This ecofriendly blend for the synthesis of heterocycles reports excellent yields of products with shorter reaction times and a simple workup procedure. Evaluating these merits, this review focuses on the recent literature published on the use of choline chloride-based DESs in the synthesis of a few important heterocyclic compounds.

Isatin (1H-indole-2,3-diones) and its derivatives are a unique structure of heterocyclic molecules with great synthetic versatility and enormous biological activities of interest. Isatins have been broadly used as building blocks for the formation of a wide range of Nheterocycles. These applicable compounds undergo various reactions to form new heterocyclic compounds. The focus of this review is to summarize the recent literature and key reactions published about Pfitzinger, ring-opening, and ring expansion reactions of isatin and its derivatives during the period from 2018 to 2020. We believe this gives some insight and helps to bring about new ideas for further research.

Asymmetric reactions have made a significant advancement over the past few decades and involved the production of enantiomerically pure molecules using enantioselective organocatalysis, chiral auxiliaries/substrates, and reagents via controlling the absolute stereochemistry. The laboratory synthesis using an enantiomerically impure starting material gives a combination of enantiomers that are difficult to separate for chemists in medicine, chromatography, pharmacology, asymmetric synthesis, and studies on structure-function relationships of proteins, life sciences and mechanistic studies. This challenging step of separation can be avoided by using asymmetric synthesis. Using pharmacologically relevant scaffolds/ pharmacophores, the drug design can also be achieved using asymmetric synthesis to synthesize receptor-specific pharmacologically active chiral molecules. This approach can be used to synthesize asymmetric molecules from a wide variety of reactants using specific asymmetric conditions, which is also beneficial for the environment due to less usage and discharge of chemicals into the environment. Therefore, in this review, we have focused on the inclusive collation of diverse mechanisms in this area to encourage auxiliary studies of asymmetric reactions to develop selective, efficient, environment-friendly, and highyielding advanced processes in asymmetric reactions.

Background: The number of lipid disorders cases has risen dramatically around the world as a result of poor dietary habits, hereditary risk factors, or other diseases or medicines. Cholesteryl ester transfer protein (CETP) is a 476 amino acid lipophilic glycoprotein that helps transport cholesteryl esters and phospholipids from proatherogenic LDL and VLDL to atheroprotective HDL. CETP inhibition increases HDL cholesterol, lowers LDL cholesterol and triglycerides, rendering it a promising therapy option for hyperlipidemia and its comorbidities. Methods: In this research, fourteen benzenesulfonamides 7a-7g and 8a-8g were synthesized and identified using ¹H-NMR, ¹³C-NMR, IR and MS. The in vitro biological evaluation of 7a- 7g and 8a-8g revealed CETP inhibitory activities ranging from 15.6 to 100% at 10 μM concentration. Results: Four aromatic rings compounds bearing either m-CH3 (8c) or p-Cl (8g) were the most potent compounds with 100% CETP inhibition, while the most active compound was 7c bearing three aromatic rings and m-CH3 with an IC50 of 0.12 μM. LibDock displayed that benzenesulfonamides can form hydrophobic interactions with the side chains of Leu129, Cys13, Ala202, Val198, Leu217 and Ile215 and participate in п-п stacking with Phe441, Phe197 and Arg201 in the binding pocket of CETP. Conclusion: Pharmacophore mapping showed significant matching with the pharmacophoric features of Hypo4/8 and shape-complemented Hypo4/8 of CETP inhibitors for potent compounds.