Letters in Organic Chemistry - Volume 22, Issue 7, 2025

Isoalloxazines are the essential cofactors of flavoproteins, which are responsible for the different redox reactions in various biological processes. They can be efficiently synthesized using N-substituted 2-nitrophenylamines as a precursor. In the present communication, we report a simple and efficient method for the synthesis of N-substituted 2-nitrophenylamines in DABCO-based ionic liquids. The method offers the use of DABCO-based ionic liquids as non-conventional catalysts, which eliminates the use of any additional base with excellent yields in short reaction time, easy product isolation, high purity, and recyclability.

Wound healing is a natural phenomenon that allows tissue to repair itself after any injury. To minimize any complexity associated with wounds, they are managed with medications. Nowadays, there is growing interest in alternative sources of medication. Scientists are contemplating finding more potential in plant compounds that are promising drug targets in blood coagulation, inflammation, and wound healing research. Although there are well-established pharmaceutical products on the market for blood clotting, identifying the plant-based lead compound is challenging in hemostats and wound care. The phenomenon by which these plant compounds trigger the healing mechanism is still unknown. The current investigation aims to screen the bioactive compounds in Eupatorium adenophorum that are responsible for hemostasis activity. Gas chromatography Mass spectrometry (GC-MS) was used to perform chemical profiling of E. adenophorum’s leaf extracts in different solvents. Molecular docking was performed by using AutoDock Vina to screen the identified bioactive molecules against twenty-one target proteins found in the blood coagulation pathway. To confirm the overall structural stability of protein-ligand interactions, 100 ns molecular dynamics simulations were performed with only the A1 domain of the Von Willebrand Factor (1 AUQ), calculating RMSD (Root mean square deviation), C-alpha fluctuations, and RMSF (Root mean square fluctuations) values. Furthermore, binding energies were validated using Mechanics Poisson Boltzmann (MMPBSA) software. These ligands can be used as potential blood coagulants and wound healers after extensive in vivo investigations to assess their potential toxicological activities.

An improved strategy for the synthesis of terbinafine has been developed through the cross-coupling of (E)-aminovinyl chloride with tert-butyl acetylene using 1 mol% of 5% Pd/C as a recyclable heterogeneous catalyst under mild conditions. This is the first report on the Pd/C catalyzed Sonogashira coupling to produce the 99.9% pure terbinafine under mild conditions.

Brivaracetam is a relatively new racetam drug for the treatment of epilepsy, synthesis of which with proper stereocontrol remains challenging. Herein we describe a solvent-free lactamization method for the development of two efficient synthetic routes to brivaracetam. The key method is a one-step condensation of amines with chiral α-carboxyethyl-β-propyl butyrolactone under neat conditions that proceed through tandem decarboxylation and lactamization. The lactam obtained using benzylamine was converted to (S)-3-propyl pyrrolidinone, a key intermediate to brivaracetam. Whereas, the lactam obtained from the condensation of (S)-2-amino butanol was further transformed into brivaracetam.

A novel synthesis of cryptophycin unit A in its enantiomerically pure form was achieved. In five steps, an enantiomeric mixture of unit A was initially prepared from trans-cinnamaldehyde. Subsequently, in its enantiomerically pure forms, unit A was prepared from Rocher’s ester in six steps, involving an essential aldehyde (2R,3E)-2-methyl-4-phenylbut-3-enal. The final step of this process involved two different approaches: a Reformatsky reaction of an essential aldehyde with tertbutyl 4-bromocrotonate and the vinylogous Mukaiyama aldol reaction with O,O-Silyl ketene acetal in the presence of isopropyl alcohol and L-tryptophane-based B-phenyloxazaborolidinone, thereby resulting in the desired products in good overall yields and high enantioselectivities.

There is an urgent need to search for more efficient, better-tolerated anticancer drugs. Tranilast, a synthetic analog of tryptophan metabolite, has been shown to inhibit the growth of various cancer cells. In our previous study, the tranilast analog TRA01 [N-(3,4,5-trimethoxycinnamoyl) anthranilic acid] was identified as a promising agent against the proliferation of MCF-7 and HepG2 cell lines along with good binding affinity on the transforming growth factor beta 1 (TGFβ1) target. To further explore the structure-activity relationship, a series of N-(3,4,5-trimethoxycinnamoyl) anthranilic acid derivatives 5a–i were successfully synthesized via a two-step synthetic procedure based on N-acylation and Knoevenagel-Doebner reactions and their structures were determined using ¹H-NMR, ¹³C-NMR, and MS spectra. The derivatives (5a–i) were evaluated for in vitro activity using MTT assay and in silico docking on TGFβ1 target by AutoDockTools–1.5.6 software. The bioactivity results of 5a–i showed 12.30–27.04% and 19.13–46.23% inhibition on proliferation of MCF-7 and HepG2 cell lines at 100 µM concentration, respectively, with the fluorinated derivatives (5a and 5e) possessing the strongest inhibitory activities. The molecular docking also found the best binding affinity of 5a (-8.70 Kcal/mol) and 5e (-8.71 Kcal/mol) on the TGFβ1 target. The SAR result revealed that substituents on the benzene ring of anthranilic acid were not favored for anticancer activity. Although these derivatives exhibited weak anticancer properties, the good binding affinity to the TGFβ1 target suggested certain potential of this scaffold for further study on this target.