Catalytic Access to Chiral δ-Lactams via Nucleophilic Dearomatization of Pyridine Derivatives

Nitrogen-bearing rings are common features in the molecular structures of modern drugs, with chiral δ-lactams being an important subclass due to their known pharmacological properties. Catalytic dearomatization of preactivated pyridinium ion derivatives emerged as a powerful method for the rapid construction of chiral N-heterocycles. However, direct catalytic dearomatization of simple pyridine derivatives are scarce and methodologies yielding chiral δ-lactams are yet to be developed. Herein, we describe an enantioselective C4-dearomatization of methoxypyridine derivatives for the preparation of functionalised enantioenriched δ-lactams using chiral copper catalysis. Experimental ¹³C kinetic isotope effects and density functional theory calculations shed light on the reaction mechanism and the origin of enantioselectivity.     

Effect of Soaking Conditions and Fuzzy Analytical Method for Producing the Quick-Cooking Black Jasmine Rice

The quick-cooking rice product is an interesting product for the market which is easy to cook, with good sensorial qualities and health benefits. This work aimed to study the effect of the soaking conditions, namely baking powder concentration (0.1, 0.2, or 0.3%), soaking temperature (room temperature, 50 or 60 °C), and soaking time (10, 20, or 30 min), in order to improve the physical properties and also the sensory characteristics, with high bioactive compound content, of Quick-Cooking Black Jasmine Rice (QBJR). The physical properties of the final product, namely the rehydration capacity, morphology, and texture, were observed. Moreover, the total phenolic, total flavonoid, and total anthocyanin were determined. The results showed that the samples with a high baking powder concentrations soaked at high temperatures for longer time affect the low rehydration capacity with a high hardness value and a decreased bioactive compound content. In addition, the sensory score including softener, flavor, and overall acceptance were lower score. Moreover, to determine the best soaking condition with complex data, the Fuzzy Analytical Method (FAM) was performed by an online FAM program. The results showed that soaking at room temperature for 30 min in 0.1% of baking powder showed the highest overall performance index of 6.52.     

Dynamic Slope Scaling Procedure and Lagrangian Relaxation with Subproblem Approximation

The dynamic slope scaling procedure (DSSP) is an efficient heuristic algorithm that provides good solutions to the fixed-charge transportation or network flow problem. However, the procedure is graphically motivated and appears unrelated to other optimization techniques. In this paper, we formulate the fixed-charge problem as a mathematical program with complementarity constraints (MPCC) and show that DSSP is equivalent to solving MPCC using Lagrangian relaxation with subproblem approximation.     

Histone Deacetylase Inhibitory Activity and Antiproliferative Potential of New [6]-Shogaol Derivatives

Twenty newly synthesized derivatives of [6]-shogaol (4) were tested for inhibitory activity against histone deacetylases. All derivatives showed moderate to good histone deacetylase inhibition at 100 µM with a slightly lower potency than the lead compound. Most potent inhibitors among the derivatives were the pyrazole products, 5j and 5k, and the Michael adduct with pyridine 4c and benzothiazole 4d, with IC₅₀ values of 51, 65, 61 and 60 µM, respectively. They were further evaluated for isoform selectivity via a molecular docking study. Compound 4d showed the best selectivity towards HDAC3, whereas compound 5k showed the best selectivity towards HDAC2. The potential derivatives were tested on five cancer cell lines, including human cervical cancer (HeLa), human colon cancer (HCT116), human breast adenocarcinoma cancer (MCF-7), and cholangiocarcinoma (KKU100 and KKU-M213B) cells with MTT-based assay. The most active histone deacetylase inhibitor 5j exhibited the best antiproliferative activity against HeLa, HCT116, and MCF-7, with IC₅₀ values of 8.09, 9.65 and 11.57 µM, respectively, and a selective binding to HDAC1 based on molecular docking experiments. The results suggest that these compounds can be putative candidates for the development of anticancer drugs via inhibiting HDACs.     

A heuristic method for the minimum toll booth problem

This paper addresses the toll pricing problem in which the objective is to minimize the number of required toll facilities in a traffic network. The problem is shown to be NP-hard. To obtain a solution in a reasonable time, an effective metaheuristic algorithm is developed. The algorithm uses a local search technique in which the neighborhood function employs the dynamic slope scaling procedure to deal with the fixed charge nature of the objective function. Numerical results from 50 randomly generated and three real networks are reported.     

Benders decomposition for variational inequalities

The partitioning technique of J.F. Benders, which was generalized to nonlinear programming by Geoffrion, is further generalized to linearly constrained variational inequality problems. The conditions under which such a generalization is possible and appropriate are examined.An important area of application is the asymmetric traffic assignment problem for which the decomposition assumes a simple and effective form. A computational example demonstrates the algorithm.This research was supported in part by NFS grants ECE-8420830 and ECS-8516365.     

Referees 1975

Notice

Referees 1975     

Discrete-time dynamic traffic assignment models with periodic planning horizon: system optimum

This paper proposes a system optimal dynamic traffic assignment model that does not require the network to be empty at the beginning or at the end of the planning horizon. The model assumes that link travel times depend on traffic densities and uses a discretized planning horizon. The resulting formulation is a nonlinear program with binary variables and a time-expanded network structure. Under a relatively mild condition, the nonlinear program has a feasible solution. When necessary, constraints can be added to ensure that the solution satisfies the First-In-First-Out condition. Also included are approximation schemes based on linear integer programs that can provide solutions arbitrarily close to that of the original nonlinear problem.