Novel pleuromutilin derivatives conjugated with phenyl-sulfide and boron-containing moieties as potent antibacterial agents against antibiotic-resistant bacteria.

In response to the escalating threat of microbial resistance, a series of novel pleuromutilin derivatives, conjugated with phenyl-sulfide and boron-containing moieties, were designed and synthesized. Most derivatives, especially 14b and 16b, demonstrated significant efficacy against Gram-positive bacteria, including multidrug-resistant strains, as well as pleuromutilin-resistant strains. Compound 16b showed high stability in the liver microsomes of rats and humans, along with acceptable tolerance in vitro and in vivo.

Exploration and Biological Evaluation of 1,3-Diamino-7-pyrrol[3,2-]quinazoline Derivatives as Dihydrofolate Reductase Inhibitors.

Dihydrofolate reductase (DHFR), a core enzyme of folate metabolism, plays a crucial role in the biosynthesis of purines and thymidylate for cell proliferation and growth in both prokaryotic and eukaryotic cells. However, the development of new DHFR inhibitors is challenging due to the limited number of scaffolds available for drug development. Hence, we designed and synthesized a new class of DHFR inhibitors with a 1,3-diamino-7-pyrrol[3,2-]quinazoline derivative (PQD) structure bearing condensed rings.

Discovery of isatin-β-methyldithiocarbazate derivatives as New Delhi metallo- β-lactamase-1 (NDM-1) inhibitors against NDM-1 producing clinical isolates.

New Delhi metallo-β-lactamase-1 (NDM-1) poses a threat to public health due to its capability to hydrolyze nearly all β-lactam antibiotics, leaving limited treatment options for NDM-1 positive pathogens. Regrettably, there are presently no effective NDM-1 inhibitors in clinical use. This compels us to seek new compounds to combat multi-drug resistant bacterial infections (MDR).

Design, synthesis and antibacterial evaluation of pleuromutilin derivatives.

We report herein the design, synthesis, and structure-activity relationship studies of pleuromutilin derivatives containing urea/thiourea functionalities. The antibacterial activities of these new pleuromutilin derivatives were evaluated in vitro against Gram-positive pathogens (GPPs) (Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecium) and Mycoplasma pneumoniae by the broth dilution method. Most of the targeted compounds exhibit good potency in inhibiting the growth of pathogens including Methicillin-susceptible S.

Synthesis and anti-tumor activity evaluation of salinomycin C20--alkyl/benzyl oxime derivatives.

Seventeen C20--alkyl/benzyl oxime derivatives were synthesized by a concise and effective method. Most of these derivatives showed tens to several hundred nanomolar IC values against HT-29 colorectal, HGC-27 gastric and MDA-MB-231 breast cancer cells, whose antiproliferative activity is 15-240 fold better than that of salinomycin. The C20-oxime etherified derivatives can coordinate potassium ions, and further adjust the cytosolic Ca concentrations in HT-29 cells.

A General Strategy to Synthesize ADP-7-Azido-heptose and ADP-Azido-mannoses and Their Heptosyltransferase Binding Properties.

The multistep synthesis of a novel ADP-7-azido-7-deoxy-l--β-d--heptopyranoside and several analogues as heptosyltransferase ligands is described. The synthesis of the key intermediate heptoside-1-β-phosphate involved a β-stereoselective phosphorylation of lactol employing diallyl chlorophosphate as a phosphorylating reagent. Five deprotected nucleotide sugars were generated by this synthetic sequence and evaluated as heptosyltransferase substrates (, ).

Cobalt(ii)-catalyzed benzylic oxidations with potassium persulfate in TFA/TFAA.

A cobalt-catalyzed C(sp)-H oxygenation reaction to furnish aldehyde was herein reported. This transformation demonstrated high chemo-selectivity, and tolerated various methylarenes bearing electron-withdrawing substituents. This reaction provided rapid access to diverse aldehydes form methylarenes.

A Useful Synthesis of 2-Acylamino-1,3,4-oxadiazoles from Acylthiosemicarbazides Using Potassium Iodate and the Discovery of New Antibacterial Compounds.

A useful method for the synthesis of 2-acylamino-1,3,4-oxadiazoles was developed. By using potassium iodate as an oxidant in water at 60 °C, a wide range of 2-acylamino-1,3,4-oxadiazoles were afforded in moderate to excellent yields within two hours. This method could provide a facile shortcut to generate a series of 2-acylamino-1,3,4-oxadiazoles in medicinal chemistry.

Multigram-scale synthesis of l,d-heptoside using a Fleming-Tamao oxidation promoted by mercuric trifluoroacetate.

An efficient multigram-scale synthesis of methyl 2,3,4,6-tetra-O-benzyl-l-glycero-α-d-manno-heptopyranoside from methyl 2,3,4-tri-O-benzyl-α-d-mannopyranoside is reported. It involves a sequence of Swern oxidation, Grignard addition and Fleming-Tamao reactions. The resulting scaffold was used as a precursor to design a small library of clickable l-heptosides.

Theoretical and Experimental Study of Bimetal-Pipe Hydroforming.

The corrosion of oil country tubular goods (OCTG) gets more and more serious especially in the acidic environment. So, it is very important to develop a perfect anticorrosion technology for exploring sour oil and gas fields economically and safely. Analysis indicates that the bimetal-pipe (BP) which consists of the base layer of low carbon steel and a corrosion resistant alloy (CRA) cladding layer is an economic and reliable anticorrosion technology and has broad application prospects in the transportation of acid medium.

β-Stereoselective phosphorylations applied to the synthesis of ADP- and polyprenyl-β-mannopyranosides.

An efficient and convenient synthetic route to glycosyl 1-β-phosphates has been developed using diallyl chlorophosphate as a phosphorylating agent with 4-N,N-dimethylaminopyridine under mild conditions. Diallyl-glycosyl 1-β-phosphate triesters of D-manno, L-glycero-D-manno-hepto-, D-gluco-, D-galacto-, and L-fuco-pyranose as well as lactose have been obtained by this strategy in good yields and excellent β-selectivities. Furthermore, the diallyl 6-azido-mannosyl 1-β-phosphate 2 was deprotected under mild conditions and converted into potentially clickable analogues of β-mannosyl phosphoisoprenoids I and ADP-heptose II.

Vulgarisin A, a new diterpenoid with a rare 5/6/4/5 ring skeleton from the Chinese medicinal plant Prunella vulgaris.

Vulgarisin A (1), a new diterpenoid with an unprecedented 5/6/4/5 fused tetracyclic ring skeleton, has been isolated from the medicinal plant Prunella vulgaris Linn. Its structure was characterized by extensive spectroscopic methods, and the absolute configuration was secured by single crystal X-ray diffraction analysis. Compound 1 showed weak cytotoxicity against human lung carcinoma A549 cells with an IC50 value of 57.

A novel base-induced isomerization gives access to unprecedented (E)-exo-glycals.

Bump the base: This study reports the discovery of the base-induced Z-to-E isomerization of exo-glycals bearing an electron-withdrawing group (EWG). The scope of this novel transformation regarding the carbohydrate unit is also discussed. After elucidating the mechanism, preparation of novel (E)-exo- glycals was performed (TBS = tert-butyldimethylsilyl).

[Study on the chemical constituents of Humulus scandens].

Objective: To study the chemical constituents of Humulus scandens.

Methods: The compounds were isolated by column chromatography on silica gel and Sephadex LH-20. The structures were identified by means of IR, 1H-NMR,13C-NMR and MS analyses.