Copper-catalyzed oxidative coupling of carboxylic acids with formamides for the synthesis of α,β-unsaturated amides

A novel and efficient protocol for the synthesis of α,β-unsaturated amides has been developed using catalytic amount of Cu(OAc)₂ and TBHP as an available oxidant. Oxidative coupling of various unsaturated carboxylic acids with N,N-disubstituted formamides was examined to furnish the desired products in good yields.     

3-取代-12-氧代-N,N-双(2-氯乙基)脱氧胆酰胺的合成及其抑制癌细胞活性

以7-脱氧胆酸(1)为原料,由Jones试剂氧化得到3,12-二氧代-7-脱氧胆酸(2),然后与双(2-氯乙基)胺反应,得到3,12-二氧代-N,N-双(2-氯乙基)-7-脱氧胆酰胺(4),进一步通过对化合物4中的3-位羰基进行官能团转换,得到2个3-位分别被肟基、缩胺硫腙基取代的12-氧代-N,N-双(2-氯乙基)-7-脱氧胆酰胺类型化合物。同时,初步测试了合成物对肿瘤细胞增殖抑制活性,结果表明,化合物对宫颈癌细胞的生长有显著的抑制活性。     

Sugar-derived cyclic imines: one-pot synthesis and direct functionalization

A simple method for the synthesis of sugar-derived imines by a Schwartz's reagent reduction of easily available sugar lactams has been described. A direct addition of nucleophiles to the generated in situ cyclic imines and subsequent deprotection of hydroxyl function allows to convert sugar lactams in polyhydroxylated pyrrolidines and piperidines.     

Some electrophilic reactivity studies of di-(2-indolyl)dibenzofurans and di-(2-indolyl)carbazoles

3,6-Bis-(2-indolyl)dibenzofurans 1,2, and carbazoles 3–6 underwent a range of electrophilic substitution reactions to produce formyl indoles 7–12, biindolyls 24–28 and 33–34, glyoxylamides 40–42, and amides 48.     

Heavy Alkali Metal Manganate Complexes: Synthesis,Structures and Solvent-Induced Dissociation Effects

Rare examples of heavier alkali metal manganates [{(AM)Mn(CH₂SiMe₃)(N^‘Ar)₂}_∞] (AM=K, Rb, or Cs) [N^‘Ar=N(SiMe₃)(Dipp), where Dipp=2,6-iPr₂-C₆H₃] have been synthesised with the Rb and Cs examples crystallographically characterised. These heaviest manganates crystallise as polymeric zig-zag chains propagated by AM⋅⋅⋅π-arene interactions. Key to their preparation is to avoid Lewis base donor solvents. In contrast, using multidentate nitrogen donors encourages ligand scrambling leading to redistribution of these bimetallic manganate compounds into their corresponding homometallic species as witnessed for the complete Li - Cs series. Adding to the few known crystallographically characterised unsolvated and solvated rubidium and caesium s-block metal amides, six new derivatives ([{AM(N^‘Ar)}_∞], [{AM(N^‘Ar)⋅TMEDA}_∞], and [{AM(N^‘Ar)⋅PMDETA}_∞] where AM=Rb or Cs) have been structurally authenticated. Utilising monodentate diethyl ether as a donor, it was also possible to isolate and crystallographically characterise sodium manganate [(Et₂O)₂Na(ⁿBu)Mn[(N^‘Ar)₂], a monomeric, dinuclear structure prevented from aggregating by two blocking ether ligands bound to sodium.     

[2+3] Amide Cages by Oxidation of [2+3] Imine Cages – Revisiting Molecular Hosts for Highly Efficient Nitrate Binding

The pollution of groundwater with nitrate is a serious issue because nitrate can cause several diseases such as methemoglobinemia or cancer. Therefore, selective removal of nitrate by efficient binding to supramolecular hosts is highly desired. Here we describe how to make [2+3] amide cages in very high to quantitative yields by applying an optimized Pinnick oxidation protocol for the conversion of corresponding imine cages. By NMR titration experiments of the eight different [2+3] amide cages with nitrate, chloride and hydrogen sulfate we identified one cage with an unprecedented high selectivity towards nitrate binding vs. chloride (S=705) or hydrogensulfate (S>13500) in CD₂Cl₂/CD₃CN (1 : 3). NMR experiments as well as single-crystal structure comparison of host-guest complexes give insight into structure-property-relationships.     

In Situ Grignard Metalation Method for the Synthesis of Hauser Bases

The in situ Grignard Metalation Method (iGMM) is a straightforward one-pot procedure to quickly produce multigram amounts of Hauser bases R₂N-MgBr which are valuable and vastly used metalation reagents and novel electrolytes for magnesium batteries. During addition of bromoethane to a suspension of Mg metal and secondary amine at room temperature in an ethereal solvent, a smooth reaction yields R₂N-MgBr under evolution of ethane within a few hours. A Schlenk equilibrium is operative, interconverting the Hauser bases into their solvated homoleptic congeners Mg(NR₂)₂ and MgBr₂ depending on the solvent. Scope and preconditions are studied, and side reactions limiting the yield have been investigated. DOSY NMR experiments and X-ray crystal structures of characteristic examples clarify aggregation in solution and the solid state.     

Amide Moieties Modulate the Antimicrobial Activities of Conjugated Oligoelectrolytes against Gram-negative Bacteria

Cationic conjugated oligoelectrolytes (COEs) are a class of compounds that can be tailored to achieve relevant in vitro antimicrobial properties with relatively low cytotoxicity against mammalian cells. Three distyrylbenzene-based COEs were designed containing amide functional groups on the side chains. Their properties were compared to two representative COEs with only quaternary ammonium groups. The optimal compound, COE2−3C−C3-Apropyl , has an antimicrobial efficacy against Escherichia coli with an MIC=2 μg mL⁻¹, even in the presence of human serum albumin low cytotoxicity (IC₅₀=740 μg mL⁻¹) and minimal hemolytic activity. Moreover, we find that amide groups increase interactions between COEs and a bacterial lipid mimic based on calcein leakage assay and allow COEs to readily permeabilize the cytoplasmic membrane of E. coli. These findings suggest that hydrogen bond forming moieties can be further applied in the molecular design of antimicrobial COEs to further improve their selectivity towards bacteria.     

The Effect of the Side Chain on Gelation Properties of Bile Acid Alkyl Amides

Six bile acid alkyl amide derivatives were studied with respect to their gelation properties. The derivatives were composed of three different bile acids with hexyl or cyclohexyl side chains. The gelation behaviour of all six compounds were studied for 36 solvents with varying polarities. Gelation was observed mainly in aromatic solvents, which is characteristic for bile-acid-based low molecular weight gelators. Out of 108 bile acid-solvent combinations, a total of 44 gel systems were formed, 28 of which from lithocholic acid derivatives, only two from deoxycholic acid derivatives, and 14 from cholic acid derivatives. The majority of the gel systems were formed from bile acids with hexyl side chains, contrary to the cyclohexyl group, which seems to be a poor gelation moiety. These results indicate that the spatial demand of the side chain is the key feature for the gelation properties of the bile acid amides.     

A General and Highly Selective Palladium‐Catalyzed Hydroamidation of 1,3‐Diynes

A chemo‐, regio‐, and stereoselective mono‐hydroamidation of (un)symmetrical 1,3‐diynes is described. Key for the success of this novel transformation is the utilization of an advanced palladium catalyst system with the specific ligand Neolephos. The synthetic value of this general approach to synthetically useful α‐alkynyl‐α, β‐unsaturated amides is showcased by diversification of several structurally complex molecules and marketed drugs. Control experiments and density‐functional theory (M06L‐SMD) computations also suggest the crucial role of the substrate in controlling the regioselectivity of unsymmetrical 1,3‐diynes.