Ming-Jung Wu

Iodine-mediated cascade cyclization of enediynes to iodinated benzo[a]carbazoles.

Treatment of N,N-dimethyl 2-[2-(2-ethynylphenyl)ethynyl]anilines (1) with 1.2 equiv of iodine in CH(2)Cl(2) gave benzo[a]carbazoles (2) in good yields. Mechanistic studies showed this reaction must go through the haloindole (3) followed by iodonium ion catalyzed atom-transfer cyclization reaction to give the benzo[a]carbazoles.

Synthetic Development and Mechanistic Study on Pd(II)-Catalyzed Cyclization of Enediynes to Benzo[a]carbazoles

Treatment of N,N-dimethyl 2-[2-(2-ethynylphenyl)ethynyl]anilines (1) with 10 mol % of palladium chloride and 2 equiv of cupric chloride in refluxing THF gave benzo[a]carbazoles (6) in good yields. A mechanistic study showed that this reaction must proceed through formation of haloindole (7) followed by a palladium(II)-catalyzed atom transfer cyclization reaction to give the benzo[a]carbazoles.

A direct anionic cyclization of 2-alkynylbenzonitrile to 3-substituted-1(2H)-isoquinolones and 3-benzylideneisoindol-2-ones initiated by methoxide addition

Treatment of 2-(2-alkylethynyl)benzonitrile with sodium methoxide in refluxing methanol for 12 h gave 3-alkyl-1(2H)-isoquinolone in modest yield. Under the same reaction conditions, methanolysis of 2-(2-arylethynyl)benzonitrile lead to the formation of 3-alkylidene isoindol-1-one. Partial hydrolysis of 2-(1-hexynyl)benzonitrile to the corresponding benzamide, followed by treatment of the benzamide with sodium methoxide in refluxing methanol gave 3-pentylidene isoindol-1-one in 49% yield. This suggests that the benzamide is not involved in this cyclization reaction.

Palladium(II)‐Catalyzed One‐Pot Syntheses of 9‐(Pyridin‐2‐yl)‐9H‐carbazoles through a Tandem CH Activation/CX (X=C or N) Formation Process

A new one-pot synthesis of 9-(pyridin-2-yl)-9H-carbazoles through the simultaneous C-H activation and palladium(II)-catalyzed cross-coupling of N-phenylpyridin-2-amines with potassium aryltrifluoroborates is presented. Silver acetate and 1,4-dioxane proved to be the best oxidant and solvent, respectively. The product yields fluctuated from modest to excellent and the reaction showed sufficient functional group tolerance. p-Benzoquinone served as an important ligand for the transmetalation and reductive elimination steps in the catalytic process. The kinetic isotope effects (k(H)/k(D)) for the first and second C-H activation/C-C or C-N formation steps were measured as 2.14 and 1.18, respectively. Finally, a rational catalytic mechanism is presented based on all experimental evidence.

Biradical formation from molecules with (Z)-7-sulfonyl-3-hexen-1,5-diyne functionalities

Abstract Molecule that contains (Z)-7-sulfonyl-3-hexen-1,5-diyne functionalities undergoes base-catalyzed isomerization to (Z)-eneyne-allene-sulfone and subsequent Myers cyclization to form aromatic products, presumably via a biradical intermediate. In the presence of a nucleophile, (Z)-eneyne-allene-sulfone served as a good Michael acceptor.

Synthesis and antitumor activity of novel enediyne-linked pyrrolo[2,1-c][1,4]benzodiazepine hybrids.

A series of novel pyrrolo[2,1-c][1,4]benzodiazepine (PBD) hybrids linked with enediyne is described. These compounds were prepared by linking C-8 of DC-81 (1) with an enediyne (10-16) through carbon chain linkers to afford PBD hybrid agents 17-23 in good yields. Most of the hybrids on human cancer cell lines exhibited higher cytotoxicity, and an increase in the sub-G1 population than 1. In a previous article, we have demonstrated that DC-81-indole conjugate agents (3-6) are potent inducers of cell apoptosis in melanoma. In the present article, we investigated whether DC-81-enediyne agents possess more cytotoxicity than 6 on human 293T cells. Our data revealed that treatment of 293T cells with DC-81-enediyne resulted in a significant increase of annexin V binding, caspase-3 degradation, and p53 arrest to identify apoptotic cells than 6. These results suggest that the DC-81-enediyne agents are more efficient in inducing apoptosis than DC-81-indole in 293T cells.

First total synthesis of antrocamphin A and its analogs as anti-inflammatory and anti-platelet aggregation agents

Naturally occurring antrocamphin A (1) is a potent anti-inflammatory compound from the edible fungus Antrodia camphorata (Taiwanofungus camphoratus), whose wild fruiting body is used as a valuable folk medicine in Taiwan. This study is the first total synthesis of antrocamphin A (1) and its analogs. Their inhibition ability on NO release, superoxide anion generation, elastase release and platelet aggregation are reported herein.

Transition metal-catalyzed cascade cyclization of aryldiynes to halogenated benzo[b]naphtho[2,1-d]thiophene derivatives.

Treatment of 2-(2-(2-(2-substituted ethynyl)phenyl)ethynyl)thioanisoles (1) with 5 mol % of Ph3PAuCl/AgSbF6 and 2 equiv of NIS at refluxing CH2Cl2 gave iodo-substituted benzo[b]naphtho[2,1-d]thiophene (6) in good yields. Chloro- and bromo-substituted benzo[b]naphtho[2,1-d]thiophene derivatives (8 and 9) were also generated by treating compound 1 with 5 mol % of PdX2 and 3 equiv of CuX2 at refluxing THF.

Substituent Electronic Effects Govern Direct Intramolecular C–N Cyclization of N-(Biphenyl)pyridin-2-amines Induced by Hypervalent Iodine(III) Reagents

The hypervalent iodine(III) reagent-induced the direct intramolecular C-N cyclization of N-(biphenyl)pyridin-2-amines to 6-arylbenzimidazoles and N-pyridinyl-9H-carbazoles is presented. The substituent electronic effects governing the formation of benzimidazoles and carbazoles from the reaction of N-(biphenyl)pyridin-2-amines with hypervalent iodine(III) reagents is investigated. Radical trapping and UV-vis spectroscopic experiments on the detection of the cation radical are carried out. Rational mechanisms for these reactions are presented. The selective intramolecular C-N and C-O cyclization of N-(biphenyl)acetamides based on the substituent electronic effects is also presented.

Base-Mediated Cyclization Reaction of 2-(5-Hydroxy-1-pentynyl)benzonitriles to 4-Amino-2,3-dihydronaphtho[2,3-b]furanes and Synthesis of Furanonaphthoquinones

An efficient transformation of 2-(5-hydroxy-1-pentynyl)benzonitriles 5 to furanonaphthoquinones 11 is presented. Treatment of 5 with 1.5 equiv of NaOMe in DMSO at 140 °C for 0.5 h gave 6 in good yields. Conversion of 6 to 11 was carried out by oxidation of 6 with Fremys salt and KH2PO4 in acetone and water, followed by dehydrogenation using palladium on charcoal in diphenylether at reflux temperature.