Jeh-Jeng Wang

Facile, selective, and regiocontrolled synthesis of oxazolines and oxazoles mediated by ZnI2 and FeCl3.

An expedient method for a direct approach to the selective and regiocontrolled synthesis of 2-oxazolines and 2-oxazoles mediated by ZnI(2) and FeCl(3) is described. A Lewis acid promoted cyclization of acetylenic amide with various functionalities was well tolerated to give 2-oxazolines and 2-oxazoles in good to excellent yields under mild reaction conditions.

I2–TBHP-Catalyzed Oxidative Cross-Coupling of N-Sulfonyl Hydrazones and Isocyanides to 5-Aminopyrazoles

I2-TBHP-catalyzed oxidative cross coupling of N-sulfonyl hydrazones with isocyanides has been realized for the synthesis of 5-aminopyrazoles through formal [4 + 1] annulation via in situ azoalkene formation. Notable features are the metal/alkyne-free strategy, C-C and C-N bond formation, atom economy, catalytic I2, broad functional group tolerance, good reaction yields, shorter time, and also applicability to one-pot methodology.

Synthesis, and biological evaluation of 2-(4-aminophenyl)benzothiazole derivatives as photosensitizing agents.

Photodynamic therapy (PDT) employing exogenous photosensitizers is currently being approved for treatment of basal cell carcinoma (BCC). 2-(4-Aminophenyl)benzothiazoles (6) consist of chromophoric structure and absorb light in the UVA (315-400 nm). These results encouraged us to design and synthesize a diversity of 2-phenylbenzothiazoles (6). Studies on the apoptotic mechanism involved in photosensitive effects induced by UVA-activated 6 in BCC cells are carried out in the present article. 6-UVA-treated cells displayed several features of apoptosis, including an increase in the sub-G1 population, a significantly increased annexin V binding, and activation of caspase-3. 6-UVA induced a decrease in mitochondrial membrane potential (Deltapsi(mt)) and ATP via enhanced ROS generation and promoted phosphorylation of extracellular signal-regulated kinase (ERK) and p38 MAPK expression. These results suggest that 6-UVA elicits photosensitive effects in mitochondria processes which involve ERK and p38 activation, and ultimately lead to BCC cell apoptosis.

Metal-Free, Acid-Promoted Synthesis of Imidazole Derivatives via a Multicomponent Reaction

An expedient and metal-free synthetic route has been developed for the construction of tri- and tetrasubstituted imidazole derivatives via acid promoted multicomponent reaction methodology. The reaction proceeded smoothly with a range of functionalities to produce the imidazole scaffolds in good to excellent yields.

Palladium(0)-catalyzed single and double isonitrile insertion: a facile synthesis of benzofurans, indoles, and isatins.

A palladium(0)-catalyzed cascade process consisting of isonitrile insertion and α-Csp(3)-H cross-coupling can be achieved for the synthesis of benzofurans and indoles. The construction of isatins by a Pd-catalyzed cascade reaction incorporating double isonitrile insertion, amination, and hydrolysis has also been achieved. The key features of this work include diverse heterocycle synthesis, phosphine-ligand-free reaction conditions, a one-pot procedure, simple and commercially available starting materials, broad functional-group compatibility, and moderate to good reaction yields.

Discovery, Synthetic Methodology, and Biological Evaluation for Antiphotoaging Activity of Bicyclic[1,2,3]triazoles: In Vitro and in Vivo Studies

Novel bicyclic[1,2,3]triazoles (4, 7, 11, 15) have been synthesized using a one-pot metal free strategy with high structural diversity as photoprotective agents, and their effect on UVA-induced senescence in human dermal fibroblast cells (FB) and the associated mechanism are delineated. 11d plus UVA can induce a decrease in reactive oxygen species (ROS) production and senescence-associated β-galactosidase (SA-β-gal) activity but an increase in adenosine triphosphate (ATP) synthesis and mitochondrial membrane potential (ΔΨmt). The mRNA levels of six senescence-associated genes, matrix metalloproteinase-1 (MMP-1), was decreased, while elastin, procollagen I type I, fibronectin, COL1α1, and tissue inhibitor of metalloproteinase-1 (TIMP-1) were increased. 11d plus UVA also decreased MMP-1 and increased TIMP-1 protein levels. Additionally, the thickness of the murine dorsal skin and epidermis, by UVA, was decreased by topical 11d treatment. Our results indicate that bicyclic[1,2,3]triazoles protect UVA-induced senescence-like characteristics in FB cells, which may provide potential prevention against photoaging.

Iodine-promoted cyclization of N-propynyl amides and N-allyl amides via sulfonylation and sulfenylation

An iodine-promoted regioselective cyclization of N-propynyl/allyl amides with sulfonyl hydrazides has been developed for the synthesis of 5-methyl-arylsulfonyloxazoles and 5-methyl-arylthiooxazolines via sulfonylation and sulfenylation reactions. The notable features of this reaction are the formation of new C-S and C-O bonds, the broad functional group tolerance, and its applicability to alkyl sulfonyl hydrazides as well as internal alkynes.

Structure-function studies on Taiwan cobra long neurotoxin homolog.

A novel long neurotoxin homolog was purified from Naja naja atra (Taiwan cobra) venom using the combination of ion exchange chromatography and reverse phase high performance liquid chromatography. The determined protein sequence was essentially the same as that deduced from the cDNA amplified by reverse transcriptase-polymerase chain reaction. The long neurotoxin homolog exhibited an activity that inhibited acetylcholine-induced muscle contractions, as with N. naja atra cobrotoxin. The degree of inhibition caused by the addition of long neurotoxin homolog was approximately 70% of that observed with the addition of cobrotoxin. Unlike the well-known short and long neurotoxins, this neurotoxin homolog contained two additional cysteine residues forming a disulfide linkage in the N-terminal region. Circular dichroism measurement and computer models of the neurotoxin reveal that its secondary structure was not abundant in beta-sheet as noted with short and long neurotoxins. This less ordered structure may be associated with the lower activity noted with the long neurotoxin homolog. Together with the finding that the known long neurotoxin homologs exclusively appear in the venoms of the Naja and Bungarus genera, the long neurotoxin homologs should represent an evolutionary branch from the long and short neurotoxins in the Elapidae family.

Synthesis of sulfur-sulfur bond formation from thioamides promoted by 2,3-dichloro-5,6-dicyanobenzoquinone.

A mild and efficient synthesis of sulfur-sulfur bond formation from thioformanilides with 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) is described. Functionality on the aromatic ring plays a key role in the formation of a sulfur-sulfur bond.

BF3-Etherate-Promoted Cascade Reaction of 2-Alkynylanilines with Nitriles: One-Pot Assembly of 4-Amido-Cinnolines

A BF3-etherate-promoted cascade reaction of nitriles with 2-alkynylanilines is described. This method achieves the formation of two new C-N bonds through a reaction sequence of diazotization with t-BuONO, nucleophilic addition of the alkyne to the BF3-coordinated diazonium ion, followed by nitrile addition to the intermediary vinyl cation and hydrolysis. The method provides efficient and general access to a variety of 4-amido-cinnolines. Notable features of the method include its broad functional group tolerance and avoidance of transition metals.