Base-Promoted One-Pot Synthesis of Pyridine Derivatives via Aromatic Alkyne Annulation Using Benzamides as Nitrogen Source.

In the presence of Cs2CO3, the first simple, efficient, and one-pot procedure for the synthesis of 3,5-diaryl pyridines via a variety of aromatic terminal alkynes with benzamides as the nitrogen source in sulfolane is described. The formation of pyridine derivatives accompanies the outcome of 1,3-diaryl propenes, which are also useful intermediates in organic synthesis. Thus, pyridine ring results from a formal [2+2+1+1] cyclocondensation of three alkynes with benzamides, and one of the alkynes provides one carbon, whilst benzamides provide a nitrogen source only. A new transformation of alkynes as well as new utility of benzamide are found in this work.

Biaryl Formation via Base-Promoted Direct Coupling Reactions of Arenes with Aryl Halides.

In the absence of ligand, Cs2CO3-promoted cross-coupling reaction of arenes with cyano-/nitro-substituted aryl halides in DMSO affording biaryls is reported. The cyano/nitro group in biaryls is useful and convenient for further transformation. The formation of dibenzofurans resulting from the reactions between arenes and 1-bromo-2-iodobenzene is also reported. On the basis of control experiments and theoretical studies, a radical mechanism is proposed for the formation of biaryls.

Base-Promoted Annulation of Amidoximes with Alkynes: Simple Access to 2,4-Disubstituted Imidazoles.

An efficient construction of imidazole ring by a Cs2CO3-promoted annulation of amidoximes with terminal alkynes in DMSO has been developed. This protocol provides a simple synthetic route with high atom-utilization for the synthesis of 2,4-disubstituted imidazoles in good yields under transition-metal-free and ligand-free conditions. Internal alkynes can also undergo the annulation to give 2,4,5-trisubstituted imidazoles.

Quinazolinone Synthesis through Base-Promoted SNAr Reaction of ortho-Fluorobenzamides with Amides Followed by Cyclization.

A transition-metal-free synthesis of quinazolin-4-ones by Cs2CO3-promoted SNAr reaction of ortho-fluorobenzamides with amides followed by cyclization in dimethyl sulfoxide has been developed. The present procedure can provide efficient synthetic methods for the formation of both 2-substituted and 2,3-disubstituted quinazolin-4-one rings depending on the use of easily available starting materials and an efficient, one-pot protocol for the synthesis of the marketed drug product of methaqualone.

Congenital anomaly of coronary artery: absence of left circumflex artery.

The prevalence of congenital coronary artery anomalies is approximately 1% in the general population. They are a common cause of sudden death in younger persons. Congenital absence of the left circumflex artery is usually a benign condition but can cause symptoms of exertional angina. We present a case of a 59-year-old female who presented with complaints of chest pain. She was evaluated by the cardiology service. An invasive angiogram identified the absence of the circumflex artery, a large right coronary artery, and large septal and diagonal branches of the left main coronary artery possibly as a compensatory mechanism to supply blood to the LCx territories. It is important to define coronary anatomy as anomalies dictate which cardiac intervention should be attempted in cases of ischemia.

Base-Promoted SNAr Reactions of Fluoro- and Chloroarenes as a Route to N-Aryl Indoles and Carbazoles.

KOH/DMSO-promoted C-N bond formation via nucleophilic aromatic substitution (SNAr) between chloroarenes or fluoroarenes with indoles and carbazole under transition metal-free conditions affording the corresponding N-arylated indoles and carbazoles has been developed.

A Rare Case of Cyclical Hemothorax: Thoracic Endometriosis Syndrome.

Endometriosis is a common condition in which endometrial cells and stroma are deposited in extrauterine sites. Its prevalence has been estimated to be 10% of reproductive age females. It is commonly found in the pelvis; however, it may be found in the abdomen, thorax, brain, or skin. Thoracic involvement is a relatively rare presentation of this common disease. Thoracic endometriosis commonly presents as pneumothorax in 73% of patients. A rarer presentation of thoracic endometriosis is hemothorax (<14%) or hemoptysis (7%). Thoracic endometriosis is an uncommon cause of a pleural effusion. We present a case of 28-year-old African American female with no other medical conditions. She presented to the hospital with worsening right-sided pleuritic chest pain, dyspnea, and menorrhagia. She had been complaining of pleuritic chest pain for 5 years, the onset of which corresponds to the start of her menstrual cycle and is relieved with cessation of menses. Initial laboratory studies revealed a severe microcytic anemia with normal coagulation profile. Chest X-ray showed small right pleural effusion and suspicious for airspace disease. A computed tomography (CT) of chest was ordered for further clarification and identified large right pleural effusion. CT-guided thoracentesis removed 500 ml of serosanguinous fluid consisting of blood elements. There can be multiple sites involved with endometriosis and can present with wide range of symptoms that occur periodically with menses in young woman. The history and pleural fluid findings of this case are suggestive of Thoracic Endometriosis Syndrome. The diagnosis of this is often missed or delayed by clinicians, which can result in recurrent hospitalization and other complications. As internists we should be suspicious of atypical presentations of endometriosis and treat them early before complications develop. This case also highlights the importance of suspecting atypical etiologies for pleural effusion.

Microbial transformation of anti-cancer steroid exemestane and cytotoxicity of its metabolites against cancer cell lines.

BACKGROUND: Microbial transformation of steroids has been extensively used for the synthesis of steroidal drugs, that often yield novel analogues, not easy to obtain by chemical synthesis. We report here fungal transformation of a synthetic steroidal drug, exemestane, used for the treatment of breast cancer and function through inhibition of aromatase enzyme. RESULTS: Microbial transformation of anti-cancer steroid, exemestane (1), was investigated by using two filamentous fungi. Incubation of 1 with fungi Macrophomina phaseolina, and Fusarium lini afforded three new, 11α-hydroxy-6-methylene-androsta-1, 4-diene-3,17-dione (2), 16ß, 17ß-dihydroxy-6-methylene-androsta-1, 4-diene-3-one (3), and 17ß-hydroxy-6-methylene-androsta-1, 4-diene-3, 16-dione (4), and one known metabolites, 17ß-hydroxy-6-methylene-androsta-1, 4-diene-3-one (5). Their structures were deduced spectroscopically. Compared to 1 (steroidal aromatase inactivator), the transformed metabolites were also evaluated for cytotoxic activity by using a cell viability assay against cancer cell lines (HeLa and PC3). Metabolite 2 was found to be moderately active against both the cell lines. CONCLUSIONS: Biotransformation of exemestane (1) provides an efficient method for the synthesis of new analogues of 1. The metabolites were obtained as a result of reduction of double bond and hydroxylation. The transformed product 2 exhibited a moderate activity against cancer cell lines (HeLa and PC3). These transformed products can be studied for their potential as drug candidates.