ABSTRACT
A triflate salt-catalyzed nonhydrolytic method for the deacylation of N-acylsulfonamides and subsequent one-pot condensation of the newly formed sulfonamides with N,N-dimethylformamide dimethyl acetal to provide N-sulfonylamidines is presented. A range of aliphatic and aromatic N-acylsulfonamides bearing various N-acyl groups such as acetyl, propionyl, butyrl, isobutyryl, octanoyl, benzoyl, 2-phenylacetyl, and sterically hindered pivaloyl are readily transformed into the corresponding N-sulfonylamidines in good to excellent yields. A variety of functional groups including halogeno, keto, nitro, cyano, hydroxyl, ether, and carboxylic ester are tolerated intact.
ABSTRACT
Transacylation of N-acylsulfonamides, which replaces the N-acyl group with a new one, is a challenging and underdeveloped fundamental transformation. Herein, a general method for transacylation of N-acylsulfonamides is presented. The transformation is enabled by coincident catalytic reactivities of FeCl3 for nonhydrolytic deacylation of N-acylsulfonamides and subsequent acylation of the resultant sulfonamides and can be conducted either stepwise or in a one-pot manner. GaCl3 and RuCl3·xH2O are similarly effective for the reaction. This method is mild, efficient, and operationally simple. A variety of functional groups such as halogeno, keto, nitro, cyano, ether, and ester are well tolerated, providing the transacylation products in good to excellent yields.
ABSTRACT
The chemoselective cleavage of C-N bonds of amides, sulfonamides, and acylsulfonamides by aluminum halides is described. AlCl3 and AlI3 display complementary reactivities toward N-alkyl and N-acyl moieties. N-Alkylacylsulfonamides, secondary N-(tert-butyl)sulfonamides, and tertiary N-(tert-butyl)amides undergo N-dealkylation upon treatments with AlI3 generated in situ from aluminum and iodine in acetonitrile. In contrast, AlCl3 preferentially cleaves N-acyl groups of tertiary and secondary sulfonamides.
ABSTRACT
A one-pot procedure for deprotecting carboxylic esters under nonhydrolytic conditions is described. Typical alkyl carboxylates are readily deblocked to the carboxylic acids by the action of aluminum powder and iodine in anhydrous acetonitrile. Cleavage of lactones affords the corresponding ω-iodoalkylcarboxylic acids. Aryl acetylates undergo deacetylation with the participation of the neighboring group. This method enables the selective cleavage of alkyl carboxylic esters in the presence of aryl esters.
ABSTRACT
A total of 26 compounds based on osthole skeleton were designed, synthesized. Their cytoprotective abilities of antioxidation, anti-inflammation and Aß42(Amyloid ß-protein 42)-induced neurotoxicity were evaluated by MTT assays. Mechanism of the action of selected compounds were investigated by molecular docking. AlogP, logS and blood-brain barrier (BBB) permeability of all these compounds were simulated by admetSAR. Most of the compounds showed better antioxidative and anti-inflammatory activities compared with osthole, especially OST7 and OST17. The compound OST7 showed relative high activity in neuroprotection against H2O2 (45.7 ± 5.5%), oxygen glucose deprivation (64.6 ± 4.8%) and Aß42 (61.4 ± 5.2%) at a low concentration of 10 µM. EC50 of selected compounds were measured in both H2O2 and OGD induced cytotoxicity models. Moreover, NO inhibiting ability of OST17(50.4 ± 7.1%) already surpassed the positive drug indomethacin. The structure activity relationship study indicated that introduction of piperazine group, tetrahydropyrrole group and aromatic amine group might be beneficial for enhancement of osthole neuroprotective properties. Molecular docking explained that the reason OST7 exhibited relatively stronger neuroprotection against Aß because of the greater area of interactions between molecule and target protein. OST7 and OST17 both provided novel methods to investigate osthole as anti-AD drugs.
Subject(s)
Amyloid beta-Peptides/metabolism , Coumarins/chemistry , Coumarins/pharmacology , Drug Design , Neuroprotective Agents/chemistry , Neuroprotective Agents/pharmacology , Peptide Fragments/metabolism , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Amyloid beta-Peptides/antagonists & inhibitors , Humans , Molecular Docking Simulation , Peptide Fragments/antagonists & inhibitors , Structure-Activity RelationshipABSTRACT
Aluminum triiodide is harnessed by N,N-dimethylformamide dimethyl acetal (DMF-DMA) for the selective cleavage of ethers via neighboring group participation. Various acid-labile functional groups, including carboxylate, allyl, tert-butyldimethylsilyl (TBS), and tert-butoxycarbonyl (Boc), suffer the conditions intact. The method offers an efficient approach to cleaving catechol monoalkyl ethers and to uncovering phenols from acetal-type protecting groups such as methoxymethyl (MOM), methoxyethoxymethyl (MEM), and tetrahydropyranyl (THP) chemoselectively.
ABSTRACT
In addition to Diels-Alder and hetero-Diels-Alder reactions, tetrafluoro-o-benzoquinone (o-fluoranil) undergoes nucleophilic additions, addition-eliminations, dioxole formation, and charge-transfer complexation, reacting at every site on the molecular skeleton. It also effects dehydrogenations and other oxidations. The quinone can function as a (CF)(4) synthon.
ABSTRACT
In the absence of significant steric effects, Diels-Alder reactions of the title quinone generally take place with preservation of configuration, and are therefore probably concerted. However, hybrid density functional calculations indicate that often these reactions are highly asynchronous. Steric hindrance can result in reaction at quinone oxygen instead of carbon. Preference for endo over exo cycloaddition is observed, and is reinforced by a repulsive secondary orbital interaction in exo transition states.
ABSTRACT
Unexpected fluorescence enhancement has been observed during the coaggregation process between naphthylethyl lauryl ether (the fluorescence probe) and vitamin E acetate in aqueous organic binary solutions. Variant aggregators were used to study the influence of structure features on the enhancement. The experiments indicate that a long hydrophobic hydrocarbon chain is of necessity for coaggregation, and a flat group is crucial for the fluorescence enhancement. No enhancement was observed at the absence of coaggregation. The enhancement was attributed to the hindrance of rotations and prolonged life time of the probe by steric hindrance of flat groups in coaggregate. Structure features of aggregates of variant aggregators have also been discussed.