Total Synthesis of Albicidin: A Lead Structure from Xanthomonas albilineans for Potent Antibacterial Gyrase Inhibitors

The peptide antibiotic albicidin, which is synthesized by the plant pathogenic bacterium Xanthomonas albilineans, displays remarkable antibacterial activity against various Gram‐positive and Gram‐negative microorganisms. The low amounts of albicidin obtainable from the producing organism or through heterologous expression are limiting factors in providing sufficient material for bioactivity profiling and structure–activity studies. Therefore, we developed a convergent total synthesis route toward albicidin. The unexpectedly difficult formation of amide bonds between the aromatic amino acids was achieved through a triphosgene‐mediated coupling strategy. The herein presented synthesis of albicidin confirms the previously determined chemical structure and underlines the extraordinary antibacterial activity of this compound. The synthetic protocol will provide multigram amounts of albicidin for further profiling of its drug properties.     

Assignment of the absolute configuration of fischerin by computed nmr chemical shifts

The unassigned configurations of a toxic metabolite to mammals extracted from Neosartorya fischeri (fischerin) in C19, C20, C21, and C22 are assigned as R, R, R, and S, respectively. In this assignment, the extensive ab initio calculations followed by chemical shift computations are performed. Computed chemical shifts are correlated to experimental ones in order to find the correct configuration shown here.     

Synthetic Approaches towards the Sulfonamide Substituted‐1,5‐Diarylimidazole‐2‐thiones as Selective Cyclooxygense‐2 inhibitors

A new series of sulfonamide substituted 1,5‐diarylimidazole, possessing C‐2 alkylthio moiety, were synthesized for their cyclooxygense‐2 (COX‐2) inhibitory activity starting from condensation of N,N‐dibenzylaminosulfonylphenacylamine hydrochloride ( 2 ) and corresponding isothiocyanate in the presence of Et₃N, followed by alkylation in the basic medium. In concomitant with these intermediates, 2‐arylamino‐5‐arylthiazole derivatives 5 were also produced. The ratio of these two products was variable with different isothiocyanates. Final debenzylation was achieved using concentrated sulfuric acid to give the title sulfonamides 8 .     

Constrained kernelized partial least squares

Nonlinear kernel methods have been widely used to deal with nonlinear problems in latent variable methods. However, in the presence of structured noise, these methods have reduced efficacy. We have previously introduced constrained latent variable methods that make use of any available additional knowledge about the structured noise. These methods improve performance by introducing additional constraints into the algorithm. In this paper, we build upon our previous work and introduce hard‐constrained and soft‐constrained nonlinear partial least squares methods using nonlinear kernels. The addition of nonlinear kernels reduces the effects of structured noise in nonlinear spaces and improves the regression performance between the input and response variables. Copyright © 2014 John Wiley & Sons, Ltd.     

Cadmium(II) N-acetylcysteine complex formation in aqueous solution

The complex formation between Cd(II) ions and N-acetylcysteine (H(2)NAC) in aqueous solution was investigated using Cd K- and L(3)-edge X-ray absorption and (113)Cd NMR spectroscopic techniques. Two series of 0.1 M Cd(II) solutions with the total N-acetylcysteine concentration c(H2NAC) varied between 0.2-2 M were studied at pH 7.5 and 11.0, respectively. At pH = 11 a novel mononuclear [Cd(NAC)(4)](6-) complex with the average Cd-S distance 2.53(2) ? and the chemical shift δ((113)Cd) = 677 ppm was found to dominate at a concentration of the free deprotonated ligand [NAC(2-)] > 0.1 M, consistent with our previous reports on cadmium tetrathiolate complex formation with cysteine and glutathione. At pH 7.5 much higher ligand excess ([HNAC(-)] > 0.6 M) is required to make this tetrathiolate complex the major species. The (113)Cd NMR spectrum of a solution containing c(Cd(II)) = 0.5 M and c(H2NAC) = 1.0 M measured at 288 K showed three broad signals at 421, 583 and 642 ppm, which can be attributed to CdS(3)O(3), CdS(3)O and CdS(4) coordination sites, respectively, in oligomeric Cd(II)-NAC species with single thiolate bridges between the cadmium ions.     

Direct summands of direct sums of modules whose endomorphism rings have two maximal right ideals

Let M₁,…,M_n be right modules over a ring R. Suppose that the endomorphism ring of each module M_i has at most two maximal right ideals. Is it true that every direct summand of M₁⊕?⊕M_n is a direct sum of modules whose endomorphism rings also have at most two maximal right ideals? We show that the answer is negative in general, but affirmative under further hypotheses. The endomorphism ring of uniserial modules, that is, the modules whose lattice of submodules is linearly ordered under inclusion, always has at most two maximal right ideals, and Pavel P?íhoda showed in 2004 that the answer to our question is affirmative for direct sums of finitely many uniserial modules.     

On fail‐safe systems under random shocks

In practical situations, systems often suffer shocks from external stressing environments, stressing the system at random. These random shocks may have non‐ignorable effects on the system's reliability. In this paper, we provide sufficient (and necessary) conditions on components' lifetimes and their surviving probabilities from random shocks for comparing the lifetimes of two fail‐safe systems by means of the usual stochastic, hazard rate, and likelihood ratio orderings. Numerical examples are presented to highlight these theoretical results as well.     

Weak Module Amenability for Semigroup Algebras

We study the weak module amenability of Banach algebras which are Banach module over another Banach algebra with compatible actions. As an example we show that the semigroup algebra of a commutative inverse semigroup is always weakly amenable as a module over the semigroup algebra of its subsemigroup of idempotents.