Synthetic studies with the brevicidine and laterocidine lipopeptide antibiotics including analogues with enhanced properties and in vivo efficacy

Brevicidine and laterocidine are two recently discovered lipopeptide antibiotics with promising antibacterial activity. Possessing a macrocyclic core, multiple positive charges, and a lipidated N-terminus, these lipopeptides exhibit potent and selective activity against Gram-negative pathogens, including polymyxin-resistant isolates. Given the low amounts of brevicidine and laterocidine accessible by fermentation of the producing microorganisms, synthetic routes to these lipopeptides present an attractive alternative. We here report the convenient solid-phase syntheses of both brevicidine and laterocidine and confirm their potent anti-Gram-negative activities. The synthetic routes developed also provide convenient access to novel structural analogues of both brevicidine and laterocidine that display improved hydrolytic stability while maintaining potent antibacterial activity in both in vitro assays and in vivo infection models.

Convenient solid-phase approaches are described for the synthesis of brevicidine and laterocidine. Also reported are novel analogues including a laterocidine variant with enhanced hydrolytic stability and potent in vivo antibacterial activity.     

Fabrication of Cr-ZnFe2O4/S-g-C3N4 Heterojunction Enriched Charge Separation for Sunlight Responsive Photocatalytic Performance and Antibacterial Study

There has been a lot of interest in the manufacture of stable, high-efficiency photocatalysts. In this study, initially Cr doped ZnFe₂O₄ nanoparticles (NPs) were made via surfactant-assisted hydrothermal technique. Then Cr-ZnFe₂O₄ NPs were modified by incorporating S-g-C₃N₄ to enhance their photocatalytic efficiency. The morphological, structural, and bonding aspects were analyzed by XRD, FTIR, and SEM techniques. The photocatalytic efficiency of the functional Cr-ZnFe₂O₄/S-g-C₃N₄ (ZFG) heterostructure photocatalysts was examined against MB under sunlight. The produced ZFG-50 composite has the best photocatalytic performance, which is 2.4 and 3.5 times better than that of ZnFe₂O₄ and S-g-C₃N₄, respectively. Experiments revealed that the enhanced photocatalytic activity of the ZFG nanocomposite was caused by a more effective transfer and separation of photo-induced charges. The ZFG photocatalyst can use sunlight for treating polluted water, and the proposed modification of ZnFe₂O₄ using Cr and S-g-C₃N₄ is efficient, affordable, and environmentally benign. Under visible light, Gram-positive and Gram-negative bacteria were employed to ZFG-50 NCs’ antimicrobial activity. These ZFG-50 NCs also exhibit excellent antibacterial potential.     

Crystal structure and ionic conductivity of AgCr2(PO4)(P2O7)

Single crystals of a new phosphate AgCr₂(PO₄)(P₂O₇) have been prepared by the flux method and its structural and the infrared spectrum have been investigated. This compound crystallizes in the monoclinic system with the space group C2/c and the parameters are, a = 11.493 (3) Å, b = 8.486 (3) Å, c = 8.791 (2) Å, β = 114.56 (2)°, V = 779.8 (3) ųand Z = 4. Its structure consists of CrO₆ octahedra sharing corners with P₂O₇ units to form undulating chains extending infinitely along the [110] direction. These chains are connected by the phosphate tetrahedra giving rise to a 3D framework with six-sided tunnels parallel to the [101] direction, where the Ag⁺ ions are located. The infrared spectrum of this compound was interpreted on the basis of P₂O₇^4? and PO₄^3? vibrations. The appearance of ν_sP–O–P in the spectrum suggests a bent P–O–P bridge for the P₂O₇^4? ions in the compound, which is in agreement with the X-ray data. The electrical measurements allow us to obtain the activation energy of (1.36 eV) and the conductivity measurements suggest that the charge carriers through the structure are the silver captions.     

Efficient One-Pot Synthesis of Substituted Pyrido[2,3-d]pyrimidines from Vinamidinium and Chloropropeniminium Salts

A novel and efficient one-pot preparation of 6-substituted pyrido-[2,3-d]pyrimidines by cyclocondensation of 6-amino-1,3-dimethyluracil with symmetrical vinamidinium salts under basic conditions has been developed. Regioselectivity was observed with an unsymmetrical chloropropeniminium salt.     

New Selective Synthesis of Dimethyl 3-Alkylamino Itaconates

The ammonium 6 salt resulting from the reaction of the DABCO and the allyl bromide 2 was converted with good yields into a new family of dimethyl 3-amino itaconates 5.     

Regiocontrolled preparation of 3-acyl-6-aryl-2-pyridones via condensation of 3-aryl-3-chloropropeniminium salts with β-keto-amides

Α series of substituted 3-acyl-6-aryl-2-pyridones have been prepared in one-step reactions via condensation of 3-aryl-3-chloropropeniminium salts with β-keto-amides. This efficient synthesis has the advantages of high yields and simple reaction procedures.     

Regiospecific Synthesis of Disubstituted Pyridin‐2‐ones and Trisubstituted Phenols with Vinamidinium Salts

A highly efficient and versatile method for the synthesis of 3‐acyl‐5‐aryl or arylsulfonylpyridin‐2‐ones and 3‐alkyl‐5‐aryl‐2‐hydroxybenzamides in one step via regiospecific cyclocondensation reaction of β‐keto‐amides with vinamidinium salts is described.     

Synthesis in ionic liquids only: access to α-oxo-γ-thio-esters via Mukaiyama coupling

Ionic liquids are solvents general enough to conduct a multi-step process in organic synthesis. We show that both the preparation of starting materials (thioacetals and enoxysilane) as well as their coupling can be realized in such medium.     

Bare bones differential evolution

The barebones differential evolution (BBDE) is a new, almost parameter-free optimization algorithm that is a hybrid of the barebones particle swarm optimizer and differential evolution. Differential evolution is used to mutate, for each particle, the attractor associated with that particle, defined as a weighted average of its personal and neighborhood best positions. The performance of the proposed approach is investigated and compared with differential evolution, a Von Neumann particle swarm optimizer and a barebones particle swarm optimizer. The experiments conducted show that the BBDE provides excellent results with the added advantage of little, almost no parameter tuning. Moreover, the performance of the barebones differential evolution using the ring and Von Neumann neighborhood topologies is investigated. Finally, the application of the BBDE to the real-world problem of unsupervised image classification is investigated. Experimental results show that the proposed approach performs very well compared to other state-of-the-art clustering algorithms in all measured criteria.