Organic Communications Articles

A series of nitrile derivatives of Petromurin C were synthesized and assessed for their cytotoxic effects on tumor cell lines and inhibitory activity against Mycobacterium tuberculosis (M.tb H37Ra). Bromoalkyl nitriles (Br(CH2)nCN; n=1-5) and (o-, m-, p-) bromomethyl benzonitriles were used as alkylating reagents. The majority of the syntheses consisted of O-alkylated derivatives in which the two NH group were not alkylated, as expected from the treatment of petromurin C with K2CO3 in DMF followed by treatment with alkylating reagents. Similarly, treatment of Petromurin C with NaH in DMF and the treatment with alkylating reagents yielded both OR and bis-NR alkylated structures. In the first method, 7 different O-alkyl Petromurin C derivatives were obtained.  The second method yielded 7 different Petromurin-C derivatives containing both O-alkyl and bis-N-alkyl groups. Notably, compounds 1-4 and 7-10 demonstrated selective inhibitory activity against the acute myeloid leukemia cell line MV4-11, with IC50 values ranging from 12.96 to 20.00 μM. Compound 15 exhibited a minimum inhibitory concentration (MIC) of 6.25 μM against M.tb H37Ra. Importantly, all synthesized compounds showed negligible inhibition (below 50%) against human normal cell lines L-02 and 293T at a concentration of 100 μM. These findings suggest that the compounds possess high efficacy and low toxicity, indicating their potential as novel therapeutic agents for the treatment of leukemia and tuberculosis. 

A novel series of amide-based soluble epoxide hydrolase (sEH) inhibitors was rationally designed by incorporating 2,4-dichlorobenzyl and terminal heterocyclic moieties into a central amide scaffold. The target compounds were synthesized and structurally confirmed as new chemical entities using HRMS, 1H NMR, and 13C NMR spectroscopy. Molecular docking studies of the synthesized inhibitors with sEH revealed key hydrogen bonding interactions with Asp335, Tyr383, and Tyr466, along with π–π stacking interactions with His524 and Trp525, indicating their effective binding to the sEH active site.  In vitro biological evaluation showed that all synthesized derivatives exhibit potent sEH inhibitory activity at both 10 and 100 nM, with compound 11 emerging as the most promising lead for further development of potent anti-inflammatory agents.

This review focuses on the design, synthesis, and biological evaluation of novel heterocyclic compounds derived from β-diketones and cyanomethylene reagents through multicomponent and green synthetic methodologies. The study encompasses a wide range of heterocyclic scaffolds, including xanthene, chromene, chromenone, coumarin, acridine, quinoline, thiazole, thiophene, and spiro-heterocycles containing nitrogen, oxygen, and sulfur. A variety of catalysts were employed such as DBSA, P-TSA, NbCl₅, and nano-magnetic composites like CuFe₂O₄/chitosan to optimize reaction conditions for eco-friendly and high-yielding transformations. The developed synthetic strategies included one-pot, microwave-assisted, and solvent-free techniques, resulting in efficient routes to complex molecular architectures. The biological activity of the synthesized compounds was extensively screened, with several candidates exhibiting promising antimicrobial, antifungal, anticancer, and kinase-inhibitory properties. Structure-activity relationship (SAR) studies indicated that specific heteroatom substitutions enhanced biological potency, particularly in xanthene and chromenoquinoline derivatives. This work contributes to advancing heterocyclic chemistry by introducing new reaction pathways, novel molecular frameworks, and bioactive agents with potential pharmaceutical applications.

A one-pot, ionic-liquid-mediated synthesis has been developed for novel thiazolidine-4-ones containing a pyrazole and thiazole hybrid. This was achieved using a three-component reaction of 2-amino-thiazole, pyrazole-3-aldehyde, and mercaptoacetic acid in [bmim][PF6]. The whole procedure is robust and straightforward. By employing this protocol, a series of novel thiazolidine-4-ones containing pyrazole and thiazole hybrids were prepared in good yield (56-88%) and their preliminary cyclooxygenase activities were also studied and reported. The compounds 3h and 3k show the top-tier selective index for cyclooxygenase enzyme, in comparable with celecoxib as a standard.

We have thoroughly investigated the C-benzylation of pyrrole (1) using different second and third generation ionic liquids (ILs). The pyrrole C-benzylation is achieved with benzyl halides, mesylate, and tosylate selectively at C2 position in good yield. Moreover, minimal byproducts under relatively mild conditions in hexaethylene glycol substituted imidazolium based ILs (hexaEGILs) have been observed. 2-Benzyl pyrrole (3) was synthesized in high yield from pyrrole (1) and benzyl bromide (2a) in the presence of [hexaEGmim][OMs] and [dihexaEGim][OMs] as two different tailor-made ILs as catalysts (10 mol%) in MeCN at 80 oC within an hour.