Rapid Assembly of Functionalized 2H-Chromenes and 1,2-Dihydroquinolines via Microwave-Assisted Secondary Amine-Catalyzed Cascade Annulation of 2-O/N-Propargylarylaldehydes with 2,6-Dialkylphenols.

An efficient, secondary amine-catalyzed cascade annulation of 2-O/N-propargylarylaldehydes with 2,6-dialkylphenols was established to access biologically relevant functionalized 2H-chromenes and 1,2-dihydroquinolines tethered with a synthetically useful p-quinone methide scaffold in high yields under microwave irradiation and conventional heating conditions. The microwave-assisted strategy was convenient, clean, rapid, and high yielding in which the reactions were completed in just 15 min, and the yields obtained were up to 95%. This highly atom-economical domino process constructed two new C-C double bonds and a six-membered O/N-heterocyclic ring in a single synthetic operation. Its mechanism process was rationalized as involving sequential iminium ion formation, nucleophilic addition, and intramolecular annulation steps. Furthermore, the synthesized 2H-chromene derivatives were transformed into valuable indeno[2,1-c]chromenes, 5H-indeno[2,1-c]quinolines, and oxireno[2,3-c]chromene via a palladium-catalyzed double C-H bond activation process and epoxidation, respectively.

A microwave-assisted intramolecular aminopalladation-triggered domino sequence: an atom economical route to 5,10-dihydroindeno[1,2-b]indoles.

A microwave-assisted, palladium(II)-catalyzed cascade reaction of 2-alkynylanilines tethered with an α,ß-unsaturated carbonyl moiety was established to access 5,10-dihydroindeno[1,2-b]indoles in high yields (up to 84%) in a short reaction time. This operationally simple cascade process shows 100% atom economy and allows the construction of two new five-membered rings and two new (1 C-C and 1 C-N) bonds in a single synthetic attempt. The mechanistic pathway of this reaction is visualized involving intramolecular aminopalladation (5-endo-dig) followed by carbopalladation (olefin insertion) and protonolysis steps. A systematic comparison between microwave irradiation and conventional heating methods was also performed to demonstrate the supremacy of the microwave-assisted approach. This domino reaction requires no protecting groups for the amino group and the palladium catalyst needs no ligands. To the best of our knowledge, this is the first report on microwave-assisted nucleopalladation-initiated cascade transformation.

Microwave-assisted one-pot two-step imine formation-hetero-Diels-Alder-detosylation/aromatization sequence: direct access to dibenzo[b,h][1,6]naphthyridines.

A microwave-assisted, copper-catalyzed, one-pot, two-step reaction is established to access functionalized [1,6]naphthyridines in high yields (up to 96%) starting from 2-(N-propargylamino)benzaldehydes and arylamines. This rapid and operationally simple sequential reaction allowed the construction of two new heterocyclic rings and three new (2 C-C and 1 C-N) bonds in a single synthetic operation. This reaction tolerated various electron-donating and electron-withdrawing substituents well and delivered the desired products in a shorter reaction time under microwave irradiation. This reaction proceeds through a sequential imine formation, intramolecular [4 + 2] hetero-Diels-Alder reaction, and air oxidation, followed by detosylation-aromatization steps.

Target Specific Uptake of a Newly Synthesized Radiolabeled 5α-Reductase Inhibitor "Tc-99m-17-Oxo-17a-Aza-D-Homo-5-Androsten-3ß-yl Phenoxyacetate (Tc-99m-17a-Aza Steroid)" in Rat Prostatic Neoplastic Lesions.

Objective: Considering the 5α-reductase (5AR) inhibitory activity of the oximes and the importance of the ester group in increasing the anti-androgenic property, we reasoned to synthesize a compound having a lactam group in ring D and an ester group at the 3 ß position of the androsterone nucleus. The study aims to radiolabel 17-oxo-17a-aza-D-homo-5-androsten-3ß-yl phenoxyacetate (17a-aza steroid) with Tc-99m to evaluate its targeted uptake in experimentally induced prostate carcinogenesis in rats. Materials and Methods: The prediction of the optimal interaction and binding affinity of Tc-99m-17-oxo-17a-aza-D-homo-5-androsten-3 ß-ylphenoxyacetate (Tc-99m-17a-aza steroid) toward 5AR inhibitor was done using Biopredicta Vlife MDS tool. Tc-99m-17a-aza steroid was developed by direct radiolabeling protocol. The radio-pharmacological characteristics (serum stability, plasma protein-binding ability, and lipophilicity) of the complex were evaluated. Further, the bio-distribution studies of the complex were performed in rats with experimentally induced prostate carcinogenesis. Results: The in-silico analysis exhibits favorable binding of Tc-99m-17a-aza toward 5AR with D score-130.97. The radiochemical purity of Tc-99m-17a-aza was 96.79%. The radio-complex maintained stability in the rat serum for a period of 6 h (hours). Plasma protein binding and Log Po/w value were observed to be 86.23 ± 7.08% and 0.118 ± 0.045, respectively. A significantly enhanced percent-specific uptake was observed in the prostate of rats with induced prostate carcinogenesis. Conclusion: The study concludes that Tc-99m-17a-aza exhibits prostate specificity and can be explored further for its potential as a radionuclide imaging probe.

Direct Access to Bridged Tetrahydroquinolines and Chromanes via an InCl3-Catalyzed Sequential Three-Component Cascade.

A sequential three-component cascade process was developed for the synthesis of bridged tetrahydroquinolines and chromanes bearing 2,6-methanobenzo[d][1,3]diazocine and 2,6-methanobenzo[g][1,3]oxazocine scaffolds, respectively, in good yields from readily available materials. The InCl3-catalyzed reaction progressed via enamine formation, Michael addition, intramolecular cyclization, and intramolecular iminium ion cyclization steps. Notably, this high atom economic approach (-2H2O) allowed the generation of four new bonds (1 C-C and 3 C-N or 1 C-C, 1 C-O and 2 C-N) and two heterocyclic rings in a single operation.

Cancer Targeting Potential of 99mTc-Finasteride in Experimental Model of Prostate Carcinogenesis.

This study aimed to radiolabel finasteride, a novel 5α-reductase inhibitor, to evaluate its cancer targeting potential in experimental model of prostate carcinogenesis. Finasteride was effectively radiolabeled with 99mTc and showed >90% labeling efficiency. The radiopharmaceutical was found to be stable up to 6 hours in rat serum at 37°C. The blood kinetics of the 99mTc-finasteride followed a biphasic release pattern, whereby fast-release phase was observed at 15 seconds and a slow-release phase was observed after 30 minutes of administration. The plasma protein binding of the radio complex observed was 83.89%. For biodistribution studies, the rats were divided into two groups. Group I served as normal controls, while group II was subjected to carcinogen N-methyl-N-nitrosourea (MNU) and hormone testosterone propionate (T) for induction of prostate carcinogenesis, which was confirmed histopathologically. The biodistribution studies on control and carcinogen-treated rats revealed a significant percent-specific uptake in prostate, which was found to be increased significantly as a function of time. The most significant finding of the study was an increase in the percent-specific uptake in prostate of carcinogen-treated animals when compared to the percent-specific uptake in prostate of normal rats after 2 and 4 hours postinjection. The study concludes that 99mTc-finasteride possesses selectively toward prostate cancer tissue and can be explored further for its role in detection of prostate cancer.