Diastereoselective Formal 1,3-Dipolar Cycloaddition of Trifluoroethyl Amine-Derived Ketimines Enables the Desymmetrization of Cyclopentenediones.

In this research, a metal-free diastereoselective formal 1,3-dipolar cycloaddition of N-2,2,2-trifluoroethylisatin ketimines and cyclopentene-1,3-diones which can efficiently lead to the desymmetrization of cyclopentene-1,3-diones is developed. With the developed protocol, a series of tetracyclic spirooxindoles containing pyrrolidine and cyclopentane subunits can be smoothly obtained with good results (up to 99% yield and 91:9 dr). Furthermore, the methodology can be extended to trifluoromethyl-substituted iminomalonate, and the corresponding formal [3+2] cycloaddition reaction affords bicyclic heterocycles containing fused pyrrolidine and cyclopentane moieties in moderate yields with >20:1 dr. The synthetic potential of the methodology is demonstrated by the scale-up experiment and by versatile transformations of the products.

Postoperative morbidity adversely impacts long-term oncologic prognosis following hepatectomy for hepatocellular carcinoma: A multicenter observational study.

BACKGROUND & AIMS: Postoperative morbidity following hepatectomy for hepatocellular carcinoma (HCC) is common and its impact on long-term oncological outcome remains unclear. This study aimed to investigate if postoperative morbidity impacts long-term survival and recurrence following hepatectomy for HCC. METHODS: The data from a multicenter Chinese database of curative-intent hepatectomy for HCC were analyzed, and independent risks of postoperative 30-day morbidity were identified. After excluding patients with postoperative early deaths (≤90 days), early (≤2 years) and late (>2 years) recurrence rates, overall survival (OS), and time-to-recurrence (TTR) were compared between patients with and without postoperative morbidity. RESULTS: Among 2,161 patients eligible for the study, 758 (35.1%) had postoperative 30-day morbidity. Multivariable logistic regression analysis showed that diabetes mellitus, obesity, Child-Pugh grade B, cirrhosis, and intraoperative blood transfusion were independent risks of postoperative morbidity. The rates of early and late recurrence among patients with postoperative morbidity were higher than those without (50.7% vs. 38.8%, P < 0.001; and 41.7% vs. 34.1%, P = 0.017). Postoperative morbidity was associated with decreased OS (median: 48.1 vs. 91.6 months, P < 0.001) and TTR (median: 19.8 vs. 46.1 months; P < 0.001). After adjustment of confounding factors, multivariable Cox-regression analyses revealed that postoperative morbidity was associated with a 27.8% and 18.7% greater likelihood of mortality (hazard ratio 1.278; 95% confidence interval: 1.126-1.451; P < 0.001) and recurrence (1.187; 1.058-1.331; P = 0.004). CONCLUSION: This large multicenter study provides strong evidence that postoperative morbidity adversely impacts long-term oncologic prognosis after hepatectomy for HCC. The prevention and management of postoperative morbidity may be oncologically important.

Brønsted-Acid-Catalyzed Synthesis of 3-Alkoxy and 3-Sulfamido Indanones via a Tandem Cyclization.

Brønsted-acid-catalyzed allylic substitution reactions of the in situ generated 3-hydroxy indanones with alcohols and sulfamides were investigated, which provided a facile route for the synthesis of a large variety of 3-alkoxy and 3-sulfamido indanones. The key intermediates, 3-hydroxy indanones, were obtained through the intramolecular Meyer-Schuster rearrangement of o-propargyl alcohol benzaldehydes. The resulting 3-benzyloxy indanone could be selectively modified by allylic sulfonamidation and reduction reactions.

Response surface optimization of ultrasound-assisted polysaccharides extraction from pomegranate peel.

Ultrasonic technique was employed to extract polysaccharides from pomegranate peel. The optimal conditions for ultrasonic extraction of pomegranate peel polysaccharide (PPP) were determined by response surface methodology. Box-Behnken design was applied to evaluate the effects of four independent variables (ratio of water to raw material, extraction time, extraction temperature, ultrasonic power) on the yield of PPP. The correlation analysis of mathematical-regression models indicated that quadratic polynomial model could be employed to optimize the ultrasonic extraction of PPP. The optimum extraction parameters were as follows: ratio of water to raw material, 24 ml/g; extraction time, 63 min; extraction temperature, 55°C; and ultrasonic power, 148 W. Under these conditions, the polysaccharide yield was 13.658 ± 0.133% for the pomegranate peel, which well matches with the predicted value.

Matrine inhibits breast cancer growth via miR-21/PTEN/Akt pathway in MCF-7 cells.

BACKGROUND: Matrine is one of the major alkaloids extracted from Sophora flavescens and has been used clinically for breast cancer with notable therapeutic efficacy in China. However, the mechanisms are still largely unknown. METHODS: Cell viability was analyzed by MTT assay. After MCF-7 cells were treated with matrine for 48h, apoptosis was detected by flow cytometry, TUNEL assay and transmission electron microscopy, and the cell cycle distribution was also analyzed by flow cytometry. Further, the expression of PTEN, pAkt, Akt, pBad, Bad, p21(/WAF1/CIP1), and p27(/KIP1) was determined by Western blot. Changes of miR-21 level were quantified by real-time RT-PCR. After miR-21 was transfected in MCF-7 cells, PTEN protein level was measured by Western blot. RESULTS: Matrine inhibited MCF-7 cell growth in a concentration-and time-dependent manner, by inducing apoptosis and cell cycle arrest at G(1)/S phase. Matrine up-regulated PTEN by downregulating miR-21 which in turn dephosphorylated Akt, resulting in accumulation of Bad, p21(/WAF1/CIP1) and p27(/KIP1). CONCLUSION: Our study unraveled, for the first time, the ability of matrine to suppress breast cancer growth and elucidated the miR-21/PTEN/Akt pathway as a signaling mechanism for the anti-cancer action of matrine. Our findings also reinforce the notion that miRNAs can act as mediators of the therapeutic efficacy of natural medicines.