Bi(OTf)-Catalyzed Cascade Cycloaddition-Decarbonylation--Deoxygenative Aromatization between 2-Arylisatogens and Styrenes: Unveiling a Synthesis of 2,4-Diarylquinolines.

An unprecedented Bi(OTf)-catalyzed reaction between 2-arylisatogens and vinylarenes to yield 2,4-diarylquinolines is reported. The transformation occurred via a Bi-coordination to the embedded anionic nitrone oxygen, which induced a regiospecific stepwise formal [4 + 2]-cycloaddition with vinylarenes to yield a strained tricyclic intermediate, which subsequently extruded gaseous carbon monoxide. -Deoxygenative aromatization ensued to produce 2,4-diarylquinolines.

Electron Donor-Acceptor Complex-Enabled Autoinductive Conversion of Acylnitromethanes to Acylnitrile Oxides in a Photochemical Machetti-De Sarlo Reaction: Synthesis of 5-Substituted 3-Acylisoxazoles.

A photochemical Machetti-De Sarlo reaction has been developed for preparing 5-substituted 3-acylisoxazoles from acylnitromethanes and terminal alkynes. This photochemical protocol utilizes an innovative electron donor-acceptor complex, generated from acylnitromethanes, catalytic LiOBu, and 1,1,1,3,3,3-hexafluoro-2-propanol, as a photosensitizer to promote rapid conversion with a broad substrate scope in up to 80% efficiency. A sigmoidal autoinductive kinetic profile is revealed, demonstrating the novel and unique dual catalysis in the first photochemical approach of this reaction.

Inhibition of Giardia duodenalis by isocryptolepine -triazole adducts and derivatives.

Giardia duodenalis, a widespread parasitic flagellate protozoan causing giardiasis, affects millions annually, particularly impacting children and travellers. With no effective vaccine available, treatment primarily relies on the oral administration of drugs targeting trophozoites in the small intestine. However, existing medications pose challenges due to side effects and drug resistance, necessitating the exploration of novel therapeutic options.

Cholinesterase Inhibitory Activity and Molecular Docking Studies of Isocryptolepine-Triazole Adducts.

Due to the rising prevalence of Alzheimer's disease (AD), there is a pressing need for more effective drugs to treat or manage AD's symptoms. Studies have shown that cholinesterase inhibition can improve cognitive and behavioral symptoms associated with AD, by addressing the cholinergic deficit. Based on the recent development of cholinesterase inhibitors with indoloquinoline and triazole moiety, we rationalized that compounds with an isocryptolepine-triazole scaffold may also have the same biological targets.

Unveiling Route for the Synthesis of Tröger's Bases Through Azide Rearrangement.

This study introduces a novel method for producing Tröger's bases by utilizing the rearrangement chemistry of benzyl azide. This method offers a convenient and adaptable pathway for synthesizing these important molecular structures with potential for further advancements. By reacting benzyl azide derivatives with TfOH under the presence of water, this process generates iminium ion, formaldehyde, and aniline intermediates in situ.

Controllable Chemoselectivity Cascade Reactions for the Synthesis of Phenanthrenols via Palladium-Catalyzed-Suzuki/Heck Reaction and Michael Addition.

Palladium serves as a multi-functional catalyst which is controllable by tuning reaction conditions. This work demonstrated the utilization of a palladium catalyst for the synthesis of phenanthrenols by cascade palladium-catalyzed Suzuki/Heck reaction between chalcone and 2-bromophenylboronic acid, followed by Michael addition. The sequential reaction could be controlled by reactivity of the palladium catalyst in different solvents and concentrations of reagents.

Anthelmintic efficacy evaluation and mechanism of N-methylbenzo[d]oxazol-2-amine.

Parasitic roundworms cause significant sickness and mortality in animals and humans. In livestock, these nematodes have severe economic impact and result in losses in food production on a global scale. None of the currently available drugs ideally suit all treatment circumstances, and the development of drug-resistant nematode strains has become a challenge to control the infection.

Divergent synthesis of 3,4-dihydro-2-benzo[]chromen-2-one and fluorenone derivatives from -alkynylarylketones.

Our research has led to the development of a divergent synthesis approach for the synthesis of 3,4-dihydro-2-benzo[]chromen-2-one 3 and fluorenone 9 derivatives using -alkynylarylketones as common precursors. The synthesis of 3,4-dihydro-2-benzo[]chromen-2-ones 3 employed silver catalyzed ketonization to form polycarbonyl intermediates which underwent double intramolecular cyclization and decarboxylation to generate a lactone and a phenyl ring in a one-pot fashion. In addition, the same precursor could be used to prepare fluorenone derivatives 9 under acidic conditions.

Selective electrophilic cyclization of -carbonylarylacetylenols for the synthesis of cyclopenta[]naphthalenol and 2-phenylnaphthalen-1-ol analogs.

This work demonstrates a new method for the synthesis of cyclopenta[]naphthalenol and 2-phenylnaphthalen-1-ol analogs selective cyclization. -Alkynylarylkenones were employed as the common substrates that could be prepared by Sonogashira coupling between 2-haloarylacetophenone and pent-4-yn-1-ol derivatives. These precursors were used without purification to construct 2-phenylnaphthalen-1-ol intermediates by treating with (+)-CSA under heating conditions.

Mn(OAc)-Mediated One-Pot Condensation-Oxidative Annulation of 2-Alkynylanilines and 1,3-Ketoesters: Synthesis of 2-Substituted Quinolines.

A general protocol for oxidative annulation was developed for the preparation of 2-methyl-3,4-diacylquinolines directly from 2-alkynylanilines and 1,3-ketoesters. The reactions were mediated by Mn(OAc) in acetic acid at room temperature, which led to the desired quinoline products in one-pot in low to good overall yields on a wide range of substrates. The current method was convenient to conduct and proceeded under mild conditions in short reaction times.

A Mechanistically Deceiving Formation of Aryl(1-indanyl)ketones via Acid-Catalyzed Cyclization of -Alkynylarylmethanols.

The generation of reactive carbocation intermediates from -alkynylarylmethanol substrates was utilized as a means for the synthesis of aryl(1-indanyl)ketones . Substrates with a tertiary carbon at the β-position to the arene generated a carbocation intermediate via dehydration/protonation, followed by cyclization and hydration to give indanylketone products. For substrates with a quaternary carbon at that position, a carbocation intermediate was generated by protonation/elimination of water, followed by a 1,2-shift and a subsequent cyclization/hydration to give highly substituted indanylketones.

Discovery of N-methylbenzo[d]oxazol-2-amine as new anthelmintic agent through scalable protocol for the synthesis of N-alkylbenzo[d]oxazol-2-amine and N-alkylbenzo[d]thiazol-2-amine derivatives.

We discovered a lead compound, N-methylbenzo[d]oxazol-2-amine (2a), which had comparable potency to albendazole, an orally administered anthelminticdrug, against Gnathostoma spinigerum, Caenorhabditis elegans and Trichinella spiralis. Compound 2a showed about 10 times lower cytotoxicity towards normal human cell line (HEK293) than albendazole. Moreover, we have developed new processes for the synthesis of N-alkylbenzo[d]oxazol-2-amine and N-alkylbenzo[d]thiazol-2-amine derivatives via metal-free conditions.

Synergistic Lewis-Brønsted Acid Catalysis in Cascade Cyclization of -Alkynylaryl Cyclopropylketones for the Synthesis of 2,3-Dihydronaphtho[1,2-]furans.

In this work, a synthetic method for the synthesis of 2,3-dihydronaphtho[1,2-]furans employing synergistic Lewis-Brønsted Acid catalyzed cyclization of -alkynylarylcyclopropylketones has been developed. Benefits of our method included low catalyst loading, low cost of catalyst, short reaction time, and mild conditions which could be applied to a broad range of substrates, including a terminal alkyne (R = H), to provide generally high yields of the desired products. In addition, we found that 2,3-dihydronaphtho[1,2-]furan derivatives could be isomerized to give 5,6-dihydrotetraphen-7-ol anaologs under acidic conditions via Friedel-Crafts-type alkylation in good to excellent yields.

Synthesis of Naphtho[2,3-]oxazoles via Ag(I) Acid-Mediated Oxazole-Benzannulation of -Alkynylamidoarylketones.

A cascade oxazole-benzannulation for the synthesis of naphtho[2,3-]oxazoles has been developed employing -alkynylamidoarylketones as substrates. This procedure provides the advantage of preparing a wide variety of substituents on naphtho[2,3-]oxazole structures. In addition, -alkynylamidoarylketones could be prepared from easily accessible and a wide variety of commercially available starting materials.

Photoinduced C-C bond cleavage for the synthesis of 2,4-disubstituted-1-naphthols from indenone derivatives and sulfoxonium ylide.

The synthesis of 2,4-disubstituted-1-naphthols has been developed employing photomediated C-C bond cleavage (UV-LED 390 nm) of cyclopropane fused-indanones generated from the reaction between indenones and trimethylsulfoxonium chloride under basic conditions at room temperature. Seventeen substrates were examined in this study. The results showed that indenone precursors containing aryl substituents could smoothly provide the desired products in up to 81% yield.

A Compilation of Synthetic Strategies to Access the Most Utilized Indoloquinoline Motifs.

Indoloquinoline alkaloids constitute an important class of aromatic heterocycles consisting of quinoline and indole fused together in various orientations. These compounds, both natural and synthetic, often display various bioactivities which have established them to be one of the interesting medicinal targets. This class of compounds have stimulated much interest among synthetic and medicinal chemists as evidenced by growth in the number of synthetic methods to prepare and study this class of alkaloids.

Ag(I)-Catalyzed/Acid-Mediated Cascade Cyclization of ortho-Alkynylaryl-1,3-dicarbonyls to Access Arylnaphthalenelactones and Furanonaphthol Libraries via Aryl-Disengagement.

ortho-Alkynylarylketone derivatives were employed as key precursors for a one-pot synthesis of arylnaphthalenelactone and furanonaphthol libraries. In this work, we discovered a cost-effective protocol to prepare arylnaphthalenelactones in one-pot using inexpensive starting material, malonate ester, which was conveniently functionalized leading to a variety of structures. Moreover, we also found an unexpected oxy-dearylation reaction which could be used to synthesize furanonaphthol analogs.

Synthesis of Isocryptolepine-Triazole Adducts and Evaluation of Their Cytotoxic Activity.

Eighteen hybrid compounds between 8-bromo-2-fluoro-isocryptolepine (4) and 1,2,3-triazole were synthesized via azide rearrangement-annulation reaction. Compound 4 underwent regioselective N-propargylation and click reaction to form 8-bromo-2-fluoro-isocryptolepine-triazole hybrids 11 which were evaluated for cytotoxic activity. Compound 11 c containing 1-anisyltriazole was the most effective in inhibiting HepG2, HuCCA-1 and A549 cell lines (IC values of 1.

Synthesis of Benzoazepine Derivatives via Azide Rearrangement and Evaluation of Their Antianxiety Activities.

A new synthetic method for the construction of benzoazepine analogues has been developed employing -arylmethylbenzyl azide derivatives as precursors using an azide rearrangement reaction. In this work, 14 benzoazepine compounds were successfully synthesized in moderate to excellent yields. All synthetic benzoazepines were evaluated for their cytotoxicity against normal human kidney cell line (HEK cell).

Utilization of ortho-alkynylarylcarbonyl derivatives for creating structurally diverse chemical compounds.

ortho-Alkynylarylcarbonyl compounds, including ketones, aldehydes, carboxylic acids, carboxylate esters and amides, have served as useful building blocks for synthetic chemists to prepare numerous classes of important molecules. Various synthetic conversions starting from ortho-alkynylarylcarbonyl precursors are made possible by their unique and enabling structures embedded with reactive carbonyl and alkyne functional groups. These functional groups can be converted directly and independently to other compounds by several reactions.

Dibrominative Spirocyclization of 2-Butynolyl Anilides: Synthesis of -Dibromospirocyclic Benzo[][1,3]oxazines and Their Application in the Synthesis of 4-Furo[3,2-]indoles.

The combination of catalytic aqueous hydrochloric acid (HCl) and -bromosuccinimide (NBS) generated electrophilic bromine monochloride (BrCl), which readily induced spiroannulation of 2-alkynolyl anilides ( = 1-3) to form -dibromospirocyclic benzo[][1,3]oxazines in up to 92% yield. The reaction occurred under mild and metal-free conditions using EtOAc as a green solvent. The resulted spirocyclic products contained benzo[][1,3]oxazine, which was useful both as a pharmacophore and synthetic precursor.

Synthesis of 4-Acylchromene via Highly Chemoselective Iodine-Catalyzed Cyclization of Alkynylarylether Dimethylacetals.

4-Acylchromene is an important core structure found in bioactive natural products and bioactive synthetic compounds. Moreover, this core structure is frequently used as a key precursor for the synthesis of more complex molecules. In this work, we discovered that a combination of acetone and catalytic I could lead to selective activation of acetal in alkynylarylether dimethylacetal substrates while alkyne moiety remained intact.

Synthesis of neocryptolepines and carbocycle-fused quinolines and evaluation of their anticancer and antiplasmodial activities.

This study reported the discovery of novel compounds containing five-membered ring fused quinoline core structures as anticancer and antimalarial agents. Two libraries containing these core structures, neocryptolepines and carbocycle-fused quinolines, were prepared and evaluated. Compound 3h was found to be much more potent than other analogs against cancer cell lines with high selectivity.

Metal-Free Synthesis of 4-Chloroisocoumarins by TMSCl-Catalyzed NCS-Induced Chlorinative Annulation of 2-Alkynylaryloate Esters.

4-Chloroisocoumarins can be conveniently prepared from 2-alkynylaryloate esters via the activation of alkynes by electrophilic chlorine, generated in situ from -chlorosuccinimide (NCS) in the presence of 10 mol % trimethylsilyl chloride (TMSCl), which leads to 6--dig-selective chlorinative annulation to give the desired products in moderate to quantitative yields. The procedure employs readily available reagents and can be conveniently carried out on a wide scope of substrates under mild conditions (0 °C to rt). Furthermore, the reaction is scalable for gram-scale preparation of 4-chloroisocoumarins.