Helvetica Chimica Acta最新文献

All eight theoretical stereoisomers of (10S)-Ambrox have been synthesized by enzymatic polycyclization of the four geometric isomers of homofarnesol with selected squalene hopene cyclases. This includes the highly strained (+)-(8S,9S)-Ambrox, an isomer historically considered unlikely to exist. The enantiomeric (10R)-series has been prepared by a combination of diastereoselective synthesis and preparative chiral HPLC. Thus, for the first time, the synthesis and sensory properties of all but one stereoisomers of Ambrox are presented. The results solve a long standing peradventure: the commercial product (−)-Ambrox exhibits by far the strongest odour, the previously described 9-epi-Ambrox is 26 times weaker. The enantiomer difference between (−)-and (+)-Ambrox was also found much higher than in previous reports (1000 vs. 8 times). The (8R)-configuration was identified as the single most important structural feature for high odour strength.

Copper salts, which are widely applied in chemical processes, are highly toxic for aquatic life with devastating and long-lasting effects. The most sustainable measure to prevent negative impact on surface water bodies is the elimination of copper from chemical processes. In Grignard reactions, acyl chlorides are widely used in combination with copper(I) chloride to introduce acyl substituents to aromatic compounds. We demonstrate that carboxylic acid anhydrides are a competent and highly selective alternative to acyl chlorides when used in the absence of copper(I) catalysts. An integrated value stream cycle allows for recycling of the carboxylate salt byproducts by reaction with ketene, thereby reducing the waste output to almost zero. This proposed process can therefore contribute to minimizing both chemical waste and heavy metal input into water bodies.

Through the application of synthesis via molten indium flux, we have been able to expand the ternary Sc−Mn−Si system and the quaternary Sc−Mn−Al−Si system. Specifically, we report on five previously unknown chemical compounds, namely β-ScMnSi₂, Sc_4+xMn₄Si_7–2x, Sc₂Mn₄Si₅, Sc₂Mn₃Si₄, and Sc₄Mn₂AlSi₄. The compounds with the stoichiometries Sc₂Mn₄Si₅, Sc₂Mn₃Si₄, and Sc₄Mn₂AlSi₄ have previously not been reported. We find that these crystallize in the V₆Si₅, Hf₂Ru₃Si₄, and Ho₄Ni₂InGe₄ structure types, respectively. For the ternary compounds with the stoichiometries of ScMnSi₂ and Sc_4+xMn₄Si_7–2x, we find clearly deviating structural solutions compared to earlier reports. β-ScMnSi₂ is found to crystallize in the monoclinic crystal system isostructural to a supercell of the MnTiSi₂ structure and clearly deviating from the known orthorhombic α-polymorph. The compound Sc_4+xMn₄Si_7–2x is structurally very similar to Sc₄Mn₄Si₇, but exhibits the P4/nmm space group instead of I4/mmm, and is related to the Zr₄Co₄Ge₇ structure. Disorder between Si and Sc sites leads to the off-stoichiometric composition, for which we found x=0.287(5).

The review covers the results of studies published in the literature on the use of hydrazonoyl halides in the synthesis of five- (pyrazoles, thiazoles, triazoles, oxa- and thiadiazoles), six- (oxa- and thiadiazines, indazoles, pyridazines, pyrazines, tetrazines) or seven-membered (benzotriazepine) heterocycles. In the formation of these heterocycles, the main intermediate stage of the reaction is the in situ generation of nitrilimine, which enters into a cycloaddition reaction with substituted acetylenes (including in situ generated benzynes, naphthynes), allenes, activated olefins, anthranilic acid derivatives, organosulfur compounds (mercaptoaldehydes, mercaptocarboxylic acids) or with fused heterocycles. Examples are given of the formation of heterocycles by replacing the halogen atom from a hydrazonoyl halide molecule with a nucleophilic group, followed by exhaustive intramolecular cyclization into the target compound. There are discussions of reactions in which the cycloaddition of the nitrilimine to the in situ synthesized Knoevenagel condensation product (from CH-acid compounds, such as di- and monocarbonyl compounds, dinitrile malonic acid) occurs, leading to spiro-linked or conventional pyrazoles. Some syntheses of biologically active representatives are shown.

Ubiquitin (Ub) is a small, highly conserved protein essential for eukaryotic biology, and is unique in its formation of polyubiquitin chains by conjugation to one of its seven lysine side chains. Here we report that atomic tailoring of Ub side chains – i. e. the insertion, deletion, or replacement of specific atoms – has significant and unexpected consequences on the enzymatic conjugation of Ub oligomers by isopeptide bond formation mediated by E2 conjugating enzymes. These studies employed chemical synthesis and ligation methods to prepare numerous specifically tailored Ub monomers on multi-milligram scales. While some modifications including N-terminal acylation and methionine replacement did not affect protein folding or Ub chain formation with Ube2 K, other modifications had a pronounced effect of oligomerization with Ubc13/Mms2. We observed that Ala46Hse mutation obliterates the ability of this Ub monomer to accept another Ub at Lys63 in Ubc13-mediated conjugations. Exhaustive replacement of all seven lysines with shorter surrogates Orn, Dab, or Dap essentially blocks Ub chain formation, and in the case of Dap, precludes proper folding of the Ub protein.

In the past 18 years, metal-catalyzed deallylation has proven a useful tool for studying biological processes in cellulo and in the early development of innovative therapeutic catalytic strategies. This reaction is catalyzed by Ru-piano stool complexes and has been reported to be compatible with air, water, and thiol-containing compounds such as glutathione. However, little is known about the true influence of biological components on the outcome of this reaction. The results presented herein reveal that the co-solvent used in the reaction affects the complex's stability and activity in air, while the presence of glutathione contributes to minimizing the formation of N-allylated by-products. In addition, we studied the effect of air on the Ru-catalyzed deallylation. Importantly, we found that, in the presence of air, the complex is deactivated and oxidizes glutathione into its disulfide.

Thioether (sulfide) profragrances are readily prepared by 1,4-addition of alkanethiols to enones (thia-Michael reaction). Under ambient conditions, they slowly release the parent enones, thus generating a long-lasting perfumery effect. The fragrance release of profragrances obtained by 1,4-addition of S, O and N nucleophiles to enones was compared on cotton and on a hard surface for monomeric and dimeric structures. To avoid the uncontrolled generation of volatile sulfur compounds from thioethers, we investigated the extent to which different side reactions occurred next to the expected formation of enones and alkanethiols. Headspace analyses on cotton showed that enones and aldehydes were the major reaction products, whereas none or only traces of β-mercaptoketones, diketones or alkanethiols were detected. The absence of alkanethiols indicated that 1,4-elimination of thioethers was not a major pathway for fragrance release. Extraction of the cotton sheets after analysis showed that thioethers were oxidised to sulfoxides, which then can generate enones by 1,4-elimination. Thioethers, sulfoxides and sulfones were shown to efficiently release enones in practical applications.

Recent studies have demonstrated the ability of mucin O-glycans to attenuate virulence in diverse, cross-kingdom pathogens, sparking interest in their development as a novel therapeutic approach against infection. Although their virulence attenuating activity is evident, mucin glycans obtained from native sources comprise mixtures of several hundred distinct structures, and therefore the specific active glycan epitopes and molecular mechanisms of virulence attenuation remain unclear. Individual mucin glycan structures cannot be purified from native sources and are not amenable to automated synthesis; therefore, to further investigate the phenomena of virulence attenuation we have been developing convergent and scalable methods (>30 mg per target glycan) to assemble a mucin O-glycan library in sufficient scale and purity to facilitate biological studies. Previously we described a method to obtain core 1 & core 2-type mucin glycan derivatives that have since been used to identify active epitopes in Candida albicans and Vibrio cholerae. In the current study, we describe the expansion of our glycan library to include core 3 & core 4-type derivatives, increasing the structural diversity of our platform for biological evaluation.

Pyrrole-2,5-dicarboxylic acid (PDCA) is a heterocyclic aromatic dicarboxylic acid that may emerge as a new monomer for polyester production. Compared to its structurally related and bio-based furan-2,5-dicarboxylic acid (FDCA) that is already used for the production of polyethylene furanoate (PEF), PDCA shows excellent potential as its nitrogen can be targeted for further derivatization, thus enabling tuning of the properties of a PDCA containing polymer. In light of this, we recognized the need to explore efficient synthetic approaches for producing PDCAs in high yields. Here, we report a five-step synthesis route for N-substituted PDCAs starting from pyrrole, with total yields up to 42 %. The synthetic approach allowed the introduction of several different functional moieties to the pyrrole nitrogen, such as aliphatic saturated and unsaturated side-chains, as well as benzylic groups.