Latif Kelebekli

Concise synthesis of bis-homoconduritol-A was performed in a stereocontrolled manner starting from cyclooctatetraene. Tricyclic endoperoxide was prepared via photooxygenation of bicyclic dibromodiene compound. The necessary key intermediate, bis-epoxide, was quantitatively synthesized from the rearrangement reaction of endoperoxide under thermal conditions. Stereoselective ring-opening reactions of the relevant bis-epoxide with H⁺/H₂O and H⁺/AcCl were investigated. Ring-opening of bis-epoxide yielded bicyclic tetrol and haloester compounds. Acetylation of the bicyclic tetrol followed by removal of halogens with zinc powder in acetic acid yielded dibromo tetraacetate. The desired bis-homoconduritol-A was obtained in high yield by ammonolysis of the acetate groups by NH₃. The structures of all synthesized compounds were characterized by spectroscopic methods.

Introduction: This study aimed to investigate the anticancer, potential antiepileptic agents, and antioxidant potentials of 10 methyl‐substituted halogenated and methoxy conduritols, which had been previously synthesized and characterized. The presence of active functional groups within their structures suggested their potential as bioactive molecules. Both in vitro and in silico approaches were employed to assess their biological activities and therapeutic relevance. Methods: Anticancer activity was tested using the MCF‐7 breast cancer cell line and the L929 fibroblast cell line, with IC ₅₀ values calculated to evaluate cytotoxicity. Antioxidant activity was determined using DPPH, FRAP, and TAS assays. The effects of methyl‐substituted mono‐ and dimethoxy halogenated conduritol derivatives (A and B forms) on the activities of carbonic anhydrase isoenzymes hCA I and hCA II were examined spectrophotometrically. Additionally, molecular docking studies were performed against hCA I (PDB ID: 3LXE), hCA II (PDB ID: 5AML), and breast cancer proteins (PDB ID: 1JNX, 1A52). ADME/T properties of the compounds were also evaluated to predict their pharmacokinetic and safety profiles. Results: Among the synthesized derivatives, only compound 6 demonstrated notable anticancer activity, with an IC₅₀ of 20.22 μ M against MCF‐7 cells and moderate selectivity over healthy fibroblasts. The other compounds were largely inactive at the tested concentrations. Antioxidant assays demonstrated considerable free radical scavenging and reducing power. The synthesized conduritols showed strong inhibition of carbonic anhydrase isoenzymes, with Ki values ranging from 0.2083 ± 0.11 to 1.4944 ± 1.06 μ M for hCA I and 0.0857 ± 0.06 to 2.2098 ± 0.68 μ M for hCA II, outperforming standard inhibitors. Docking studies confirmed strong binding affinities to the investigated proteins, while ADME/T analysis suggested favorable pharmacokinetic properties. Conclusions: The findings indicate that methyl‐substituted halogenated and methoxy conduritols possess anticancer, potential antiepileptic agents, and antioxidant potentials. Their strong carbonic anhydrase inhibitory activities highlight their promise as potential therapeutic agents for epilepsy and glaucoma. Overall, these compounds demonstrate considerable potential as multifunctional bioactive molecules and represent promising candidates for further preclinical studies.

The concise synthesis of novel monocarbamate-triacetate with a configuration like that of cis-trans-cis-cyclohexanetetrol is reported for the first time. Photooxygenation reaction of the starting compound cyclohexadiene gave the bicyclic endoperoxide compound. Controlled reduction of the endoperoxide with thiourea afforded the allylic cis-diol compound, and subsequent reaction of the cis-diol with two equivalents of p-TsNCO led to the formation of the key compound bis-carbamate. Treatment of the bis-carbamate compound with Pd₂(dba)₃·CHCl₃ in the presence of trimethylsilyl azide (TMSN₃) produced a new monocarbamate compound as well as an oxazolidinone derivative. By oxidation of the double bond in the monocarbamate with osmium tetraoxide and subsequent acetylation with AcCl, a desired new monocarbamate triacetate compound was obtained.

The concise synthesis of O ‐methyl‐ d ‐inositol derivative and conduritol derivatives was obtained starting from p ‐benzoquinone. Spectroscopic methods have been performed for the characterization of newly synthesized compounds. Cyclitols are useful molecules with anticancer, antibiotic, antinutrient, and antileukemic activities. Inositol class molecules, known as the most important cyclitol derivatives, were examined in this study for their 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) and nitric oxide radical scavenging and butyrylcholinesterase (BChE) and glycosidase inhibition activities. It was observed that compound 5 , in particular, showed efficacy that competed with the standards in terms of both antioxidant activity and enzyme inhibitor potential. Additionally, compound 5 shows effective antimicrobial activity. The water‐soluble characteristics and lipophilic properties of the compounds were also considered and discussed. Moreover, the quantum chemical analyses were performed in light of the DFT/B3LYP/6‐311G** level computations to elucidate/compare the studied inositols’ possible reactivity directions. Additionally, the interactions of the molecules were analyzed against acetylcholinesterase (AChE), peroxiredoxin 5, and DNA gyrase by molecular docking methods. Cholinesterase inhibitors have an important status as the most important drug group used in the treatment of Alzheimer's disease today. Considering the effects of inhibition of the α‐glucosidase enzyme by inhibitors, such molecules can also be used as therapeutic components in the treatment of diabetes.

The efficient synthesis of a new class of allylic cis/trans-dicarbamates are described. Allylic diols as key intermediates of the targeted compounds were prepared in a facile way, starting from p-benzoquinone. Reaction of allylic diol compounds with p-TsNCO resulted in the formation of cis/trans-dicarbamate groups. The structure of cis/trans-dicarbamates were determined by 1H-NMR, 13C-NMR, FT-IR and elemental analysis techniques.

Concise and effective synthesis of novel halobenzoconduritols by the action of acetyl chloride is reported. Interesting monochloride and dichloride products are formed as a result of the reaction of benzoconduritol-D and 1,2,3,4-tetrahydro-1,4-epoxynaphthalene-2,3-diyl diacetate with acetyl chloride. We present surprising results bearing on the possible course and mechanism of the halobenzoconduritols synthesis. To the best of our knowledge, this reaction process represents the first example of the conversion of benzoconduritols to chloroesters. In terms of synthesis, the replacement of OH with halogen and its effects on neighboring groups were explained by the proposed mechanism (a Mattock-type mechanism). Graphical Abstract