Cladosporin, a secondary metabolite isolated from fungal sources like Cladosporium cladosporioides and Aspergillus flavus was found to exhibit selective nano-molar activity against malarial parasite Plasmodium falciparum by inhibiting parasitic protein biosynthesis. In addition, this natural product has a broad range of bioactivities including, antiparasitic, antifungal, antibacterial as well as plant growth inhibition. However, it has limited availability from the natural sources for further development. Herein, we report a modified and improved synthetic route which led us to produce this potent natural product in a gram scale. Conversion of the undesired diastereomer to desired one via Mitsunobu inversion of secondary alcohol and carbon monoxide insertion reaction towards the construction of isocoumarin unit are the key features of the present synthesis. 相似文献
First-order optimality conditions have been extensively studied for the development of algorithms for identifying locally optimal solutions. In this work, we propose two novel methods that directly exploit these conditions to expedite the solution of box-constrained global optimization problems. These methods carry out domain reduction by application of bounds tightening methods on optimality conditions. This scheme is implicit and avoids explicit generation of optimality conditions through symbolic differentation, which can be memory and time intensive. The proposed bounds tightening methods are implemented in the global solver BARON. Computational results on a test library of 327 problems demonstrate the value of our proposed approach in reducing the computational time and number of nodes required to solve these problems to global optimality. 相似文献
In the generalized balanced optimization problem (GBaOP) the objective value \({\max_{e \in S}{|c(e)-k\max(S)|}}\) is minimized over all feasible subsets S of E = {1, . . . , m}. We show that the algorithm proposed in Punnen and Aneja (Oper Res Lett 32:27–30, 2004) can be modified to ensure that the resulting solution is indeed optimal. This modification is attained at the expense of increased worst-case complexity, but still maintains polynomial solvability of various special cases that are of general interest. In particular, we show that GBaOP can be solved in polynomial time if an associated bottleneck problem can be solved in polynomial time. For the solution of this bottleneck problem, we propose two alternative approaches. 相似文献
Iron plays a vital role in several cellular functions due to its unique physiochemical properties. Iron concentration increases in the brain with age due to multiple factors. Excessive amount of iron can lead to formation of reactive oxygen species. Neurodegenerative disorders are characterized by iron supplemented increase in oxidative stress and cellular damage. There is an urgent need of novel therapies which should not only provide symptomatic relief but also be able to modulate iron accumulation in the brain. Therefore, the development of novel iron chelators as neuroprotective agents for the treatment of neurodegeneration is an emerging trend. Several iron chelators including 8-hydroxyquinoline derivatives, dopaminergic agonists and natural products are under preclinical and clinical investigations for the treatment of neurodegenerative disorders.
Surfactants are commonly incorporated into hydrogels to increase solute loading and attenuate the release rates. In this paper we focus on understanding and modeling the mechanisms of both surfactant and drug transport in hydrogels. Specifically, we focus on Brij 98 as the surfactant, Cyclosporine A (CyA) as the hydrophobic drug, and poly-hydroxy ethyl methacrylate (p-HEMA) as the polymer. The models developed here are validated by experiments conducted with gels of different thicknesses and surfactant loadings. Also the model is compared with prior experimental studies in literature. The model predicts that the percentage surfactant as well as drug release scales as 1/(surfactant loading)(0.5), and thus a four fold increase in surfactant loading leads to a two fold reduction in percentage release for both drug and surfactant at a given time. The models for the surfactant and drug release are fitted to the experimental data to obtain values of 1.44 x 10(-14) m(2)/s for CyA diffusivity and 414.4 for the partition coefficient between drug concentration inside the micelle and that in the gel. These models can be very helpful in tuning the drug release rates from hydrogels by controlling the surfactant concentration. The results also show that Brij 98 loaded p-HEMA exhibit an extended release of CyA and so contact lenses made with this material can be used for extended ocular delivery of CyA, which is an immunosuppressant drug commonly used for treatment of various ocular ailments. 相似文献
(+)-Thalictrifoline () has been synthesized from an optically resolved (+)-8-oxo-13-carboxytetrahydroprotoberberine () whose absolute configuration was established by correlation with (+)-. This determines the absolute configurations of (+)-thalictrifoline () as 13R, 14R aria (+)-corydalic acid methyl ester () as 3R, 4R. 相似文献
Metallatriazadiphosphorine complexes corresponding to [{N(PPh2NR)2}M(OAc)] and [{N(PPh2NR)2}2M], (R = Ph or SiMe3; M = Zn, Cd or Hg) have been synthesized under strictly anhydrous and inert conditions by the reaction of the acyclic bis-silylated phosphazene ligand, [HN(PPh2NSiMe3)2], or the bis-phenylated phosphazene ligand, [HN(PPh2NPh)2], with Zn, Cd and Hg acetate in 1:1 and 2:1 molar ratios. These complexes are highly soluble in common organic solvents, but unstable hydrolytically as well as thermally, even under reduced pressure. Molecular weight determinations in benzene indicated the monomeric nature of these complexes. Further, they have been characterized on the basis of elemental analysis and spectral studies: i.r. and n.m.r. (1H, 13C and 31P) that plausibly reveal a trigonal planar and tetrahedral geometry around the metal atom in the complexes. 相似文献
An unusual example of aτ+-meson decay in nuclear emulsions is described. From the measurements made on the momenta and direction of the threeπ-mesons emitted, the event is interpreted as a decay of aτ-meson according to the scheme: