Asymmetric Total Syntheses,Stereostructures, and Cytotoxicities of Marine Bromotriterpenoids Aplysiol B (Laurenmariannol) and Saiyacenol A

There are marine cytotoxic bromotriterpenoids, named the thyrsiferol family that are structurally characterized by some tetrahydropyran (THP) and tetrahydrofuran (THF) rings. The thyrsiferol family belongs to natural products that are often difficult to determine their stereostructures even by the current, highly advanced spectroscopic methods, especially in acyclic systems including stereogenic tetrasubstituted carbon centers. In such cases, it is effective to predict and synthesize the possible stereostructures. Herein, to elucidate ambiguous stereostructures and unassigned absolute configurations of aplysiol B, laurenmariannol, and saiyacenol A, members of the thyrsiferol family, we carried out their asymmetric chemical syntheses featuring 6-exo and 5-exo oxacyclizations of epoxy alcohol precursors and 6-endo bromoetherification of a bishomoallylic alcohol. In this paper, we report total assignments of their stereostructures through their asymmetric chemical syntheses and also their preliminary cytotoxic activities against some tumor cells. These results could not have been achieved without depending on asymmetric total synthesis.     

Optimisation of the ultrasound-assisted extraction of betalains and polyphenols from Amaranthus hypochondriacus var. Nutrisol

The present study optimised the ultrasound-assisted extraction (UAE) of bioactive compounds from Amaranthus hypochondriacus var. Nutrisol. Influence of temperature (25.86–54.14 °C) and ultrasonic power densities (UPD) (76.01–273.99 mW/mL) on total betalains (BT), betacyanins (BC), betaxanthins (BX), total polyphenols (TP), antioxidant activity (AA), colour parameters (L*, a*, and b*), amaranthine (A), and isoamaranthine (IA) were evaluated using response surface methodology. Moreover, betalain extraction kinetics and mass transfer coefficients (K_La) were determined for each experimental condition. BT, BC, BX, TP, AA, b*, K_La, and A were significantly affected (p < 0.05) by temperature extraction and UPD, whereas L*, a*, and IA were only affected (p < 0.05) by temperature. All response models were significantly validated with regression coefficients (R²) ranging from 87.46 to 99.29%. BT, A, IA, and K_La in UAE were 1.38, 1.65, 1.50, and 29.93 times higher than determined using conventional extraction, respectively. Optimal UAE conditions were obtained at 41.80 °C and 188.84 mW/mL using the desired function methodology. Under these conditions, the experimental values for BC, BX, BT, TP, AA, L*, a*, b*, K_La, A, and IA were closely related to the predicted values, indicating the suitability of the developed quadratic models. This study proposes a simple and efficient UAE method to obtain betalains and polyphenols with high antioxidant activity, which can be used in several applications within the food industry.     

Total Synthesis of Zephycarinatines via Photocatalytic Reductive Radical ipso-Cyclization

We report herein a nonbiomimetic strategy for the total synthesis of the plicamine-type alkaloids zephycarinatines C and D. The key feature of the synthesis is a stereoselective reductive radical ipso-cyclization using visible-light-mediated photoredox catalysis. This cyclization enabled the construction of a 6,6-spirocyclic core structure through the addition of a carbon-centered radical onto the aromatic ring. Biological evaluation of zephycarinatines and their derivatives revealed that the synthetic derivative with a keto group displays moderate inhibitory activity against LPS-induced NO production. This approach could offer future opportunities to expand the chemical diversity of plicamine-type alkaloids as well as providing useful intermediates for their syntheses.     

Unlocking the Drug Potential of the Bryostatin Family: Recent Advances in Product Synthesis and Biomedical Applications

Bryostatins are a class of naturally occurring macrocyclic lactones with a unique fast developing portfolio of clinical applications, including treatment of AIDS, Alzheimer's disease, and cancer. This comprehensive account summarizes the recent progress (2014–present) in the development of bryostatins, including their total synthesis and biomedical applications. An emphasis is placed on the discussion of bryostatin 1 , the most-studied analogue to date. This review highlights the synthetic and biological challenges of bryostatins and provides an outlook on their future development.     

正电子冲击下氦电离三重微分截面的理论计算

我们发展了一种正电子碰撞原子电离的畸变波Born近似方法， 在这个方法中，正负电子偶素通道通过一个ab initio的光学势附加到入射粒子和靶的相互作用势上，且通道对电离作用被第一次被考虑在正电子碰撞原子电离的过程中. 应用这个方法计算了在50 eV入射能量范围氦的电离的三重微分截面，计算结果和实验数据很好的符合.     

From Minutes to Years: Predicting Organotrifluoroborate Solvolysis Rates

Organotrifluoroborates solvolyze in water at rates that vary over five orders of magnitude. The negative logarithm of the solvolytic rate constant, pk_(B?F), correlates exceptionally well with the pK_a of the analogous carboxylic acid (R²=0.984). This unforeseen correlation may be of predictive value for several applications including Suzuki–Miyaura cross‐coupling reactions and the design of ¹⁸F‐organotrifluoroborate radioprosthetic groups.     

HPLC with fluorescence detection assay of perampanel,a novel AMPA receptor antagonist,in human plasma for clinical pharmacokinetic studies

Perampanel (Fycompa®), a novel α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptor antagonist, is registered for the adjunctive treatment of patients (aged ≥12 years) with refractory partial‐onset seizures. To support therapeutic drug monitoring, a simple high‐performance liquid chromatography (HPLC) assay with fluorescence detection was developed to determine perampanel concentrations in human plasma and validated to support clinical trials. Human plasma samples (1.0 mL) were processed by liquid extraction using diethyl ether, followed by chromatographic separation on a YMC Pack Pro C₁₈ column (150 × 4.6 mm i.d., 5 µm) with isocratic elution of acetonitrile–water–acetic acid–sodium acetate (840:560:3:1.8, v/v/v/w) at a flow rate of 1.0 mL/min. Column eluent was monitored at excitation and emission wavelengths of 290 and 430 nm, respectively. The assay was linear (range 1.0–500 ng/mL) and this could be extended to 25 µg/mL by 50‐fold dilution integrity. No endogenous peaks were detected in the elution of analytes in drug‐free blank human plasma from six individuals and no interference was observed with co‐medications tested. Intra‐ and inter‐batch reproducibility studies demonstrated accuracy and precision within the acceptance criteria of bioanalytical guidelines. Validation data demonstrated that our assay is simple, selective, reproducible and suitable for therapeutic drug monitoring of perampanel. Copyright © 2015 John Wiley & Sons, Ltd.