Triterpene Glycosides from Plants of the Astragalus Genus. III. Structure of Cyclounifolioside C from Astragalus unifoliolatus

The known compound cyclocantogenin (1) and a new cycloartane glycoside cyclounifolioside C (2), which has the structure 24R-cycloartan-3,6,16,24,25-pentaol 3-O--D-glucopyranoside, were isolated from roots of Astragalus unifoliolatus Bunge. The structures of the isolated compounds are established using hydrolysis and spectral data.     

Fluoroalkyl-containing lithium β-diketonates in the synthesis of 1,2,4-triazolo[1,5-a]pyrimidines

Cyclocondensation of fluorine-containing lithium -diketonates with 3-amino-1,2,4-triazoles afforded 7-fluoromethyl-1,2,4-triazolo[1,5-a]pyrimidines.     

Analytical relationships between the ionization of 1,3-dicarbonylic ligands and stability of their Cr(III), Ni(II), Co(II) and Cu(II) 1∶1 chelates

It has been demonstrated that the logarithm of the stability constant of some monochelated chromium(III) compounds, with structurally similar 1,3-dicarbonylic species, is linearly related to the negative logarithm of the acid ionization constant of the ligand. Graphical and analytical correlations which could be useful in predicting equilibrium constants of chromium(III)--diketonates, as well as other first-row transition metal derivatives, have been developed. A quantitative evaluation of the complexes stability has been carried out, providing information about the effects of ligand substituents on the equilibrium constants.     

Amyloid formation from an α-helix peptide bundle is seeded by 3(10)-helix aggregates

Transformation of proteins and peptides to fibrillar aggregates rich in β sheets underlies many diseases, but mechanistic details of these structural transitions are poorly understood. To simulate aggregation, four equivalents of a water‐soluble, α‐helical (65 %) amphipathic peptide (AEQLLQEAEQLLQEL) were assembled in parallel on an oxazole‐containing macrocyclic scaffold. The resulting 4α‐helix bundle is monomeric and even more α helical (85 %), but it is also unstable at pH 4 and undergoes concentration‐dependent conversion to β‐sheet aggregates and amyloid fibrils. Fibrils twist and grow with time, remaining flexible like rope (>1 μm long, 5–50 nm wide) with multiple strings (2 nm), before ageing to matted fibers. At pH 7 the fibrils revert back to soluble monomeric 4α‐helix bundles. During α→β folding we were able to detect soluble 3₁₀ helices in solution by using 2D‐NMR, CD and FTIR spectroscopy. This intermediate satisfies the need for peptide elongation, from the compressed α helix to the fully extended β strand/sheet, and is driven here by 3₁₀‐helix aggregation triggered in this case by template‐promoted helical bundling and by hydrogen‐bonding glutamic acid side chains. A mechanism involving α?α₄?(3₁₀)₄?(3₁₀)_n?(β)_n?m(β)_n equilibria is plausible for this peptide and also for peptides lacking hydrogen‐bonding side chains, with unfavourable equilibria slowing the α→β conversion.     

Entirely green protocol for the synthesis of β-aminoketones using saccharose as a homogenous catalyst

Saccharose was applied as an efficient and homogenous catalyst for a one-pot, three-component Mannich reaction for the formation of β-aminoketones from aromatic aldehydes, anilines, and acetophenone at ambient temperature in excellent yields. This protocol has the following advantages: mild conditions, high yields, clean reaction profiles, operational simplicity, and environmentally benign and simple work-up procedures.     

Microcontact printing of Alzheimer’s β-amyloid monomers and fibrils

Adsorption of the 40-residue Alzheimer’s β-amyloid peptide (Aβ40) on a hydrophobic surface leads to formation of potentially disease-relevant aggregates. Existing techniques are limited in characterizing the adsorbed Aβ40 and producing potentially useful Aβ40 microstructures such as microarrays and microparticles. In this paper, a novel approach based on microcontact printing (μCP) to studying and utilizing adsorption of Aβ40 monomers and fibril fragments on hydrophobic surface of polydimethylsiloxane (PDMS) stamps has been developed. By transferring the adsorbed layer from the stamp to a glass substrate, this approach allows easy measurement of thickness of the adsorbed layer. It also enables characterization of the face of the adsorbed layer in contact with the stamp surface. This face exhibits significant higher thioflavin T fluorescence than the face exposed to water, suggesting β-sheet formation induced by the PDMS surface. The intrinsic stability of the adsorbed layer is evaluated by printing the layer on a water-soluble substrate and exposing it to water vapor or water. Stable particulate microstructures in water are obtained by chemically crosslinking the adsorbed peptides. Moreover, co-micropatterning of the different states of Aβ40 (monomers and fibril fragments) is demonstrated. This μCP-based approach is simple, versatile, and holds potential for various applications.     

Aromatische Spirane, 17. Mitt.: Darstellung von anellierten und substituierten 2,2′-Spirobiindan-1-onen und 4,5′-disubstituierten 2,2′-Spirobiindanen

Summary The spiroketones9, 16, and28 were prepared by cyclisation of the carboxylic acids7c, 13b, and25c and their acid chlorides, resp. (7d, 13c, and25d) with polyphosphoric acid (PPA) or SnCl₄. The precursors of the latter compounds were synthesized by alkylation of the appropriate -ketoester1 or2 with the benzylchlorides3 or4 with NaH inDMF. Subsequent hydrogenation with Pd/C led to the desired alkylated indane-esters. The chiral compounds11, 17, and31 were obtained by Friedel-Crafts acetylation. The chiral disubstituted 2,2-Spirobiindanes22 and36 were prepared from the ketones20 and32/33 by catalytic reduction followed by Friedel-Crafts acetylation.

     

Allosteric Optical Control of a Class B G‐Protein‐Coupled Receptor

Allosteric regulation promises to open up new therapeutic avenues by increasing drug specificity at G‐protein‐coupled receptors (GPCRs). However, drug discovery efforts are at present hampered by an inability to precisely control the allosteric site. Herein, we describe the design, synthesis, and testing of PhotoETP, a light‐activated positive allosteric modulator of the glucagon‐like peptide‐1 receptor (GLP‐1R), a class B GPCR involved in the maintenance of glucose homeostasis in humans. PhotoETP potentiates Ca²⁺, cAMP, and insulin responses to glucagon‐like peptide‐1 and its metabolites following illumination of cells with blue light. PhotoETP thus provides a blueprint for the production of small‐molecule class B GPCR allosteric photoswitches, and may represent a useful tool for understanding positive cooperativity at the GLP‐1R.     

Enzymatic glycosylation of indoxyglycosides catalyzed by a novel maltose phosphorylase from Emticicia oligotrophica

Maltose phosphorylases (EC 2.4.1.8) catalyze the reversible conversion of maltose to glucose and glucose-1-phosphate in the presence of inorganic phosphate. Herein, we describe for the first time the use of a maltose phosphorylase for the synthesis of various anomerically modified diglycosides. The maltose phosphorylase used was isolated from the bacterium Emticicia oligotrophica and showed a high selectivity towards the phosphorolysis of maltose, whereas no phosphorolysis was observed using other glucose-containing disaccharides such as cellobiose, melibiose, sucrose and trehalose. The addition of glucose to various 5-bromo-4-chloro-3-indolyl-glycosides (X-sugars) was used to evaluate the promiscuity of the maltose phosphorylase, and product formation was verified by LC-ESI-MS and MALDI-TOF-MS. The simple expression and purification protocol and the use of maltose as an inexpensive starting material make this maltose phosphorylase from Emticicia oligotrophica a valuable novel biocatalyst for the synthesis of glucose-containing glycosides.