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In continuation of our commitment to the synthesis of new ring systems based on the 6,11‐dihydrodibenzo[c,f][1,2]thiazepine 5,5‐dioxide core of the antidepressant drug tianeptine, we have incorporated two‐ and/or three‐carbon bridges between the nitrogen atom of the sulfonamide moiety and the N‐, O‐ or S‐substituent at position 11 of the tricycle. The synthesis of 5 new ring systems is described and demonstrated with several target compounds. [ABSTRACT FROM AUTHOR]

α-Hydroxy-benzylphosphonates obtained by the Pudovik reaction of substituted benzaldehydes and dialkyl phosphites were added to the triple bond of dialkyl acetylenedicarboxylates. Optimum conditions involved a 24 hours stirring in the presence of 10% diazabicycloundecene in dichloromethane to afford the adducts as a mixture of predominant E - and a minor Z -isomers in 75–90% yields after flash chromatography. The structures of the geometrical isomers were confirmed by NOE- and ROE-measurements. Catalytic hydrogenation of the olefinic moiety of the adducts led to the diastereoisomers of corresponding saturated derivatives. [ABSTRACT FROM AUTHOR]

Xylobolus subpileatus is a widely distributed crust fungus reported from all continents except Antarctica, although considered a rare species in several European countries. Profound mycochemical analysis of the methanol extract of X. subpileatus resulted in the isolation of seven compounds (1–7). Among them, (3β,22E)-3-methoxy-ergosta-4,6,814,22-tetraene (1) is a new natural product, while the NMR assignment of its already known epimer (2) has been revised. In addition to a benzohydrofuran derivative fomannoxin (3), four ergostane-type triterpenes 4–7 were identified. The structure elucidation of the isolated metabolites was performed by one- and two-dimensional NMR and MS analysis. Compounds 2–7 as well as the chloroform, n-hexane, and methanol extracts of X. subpileatus were evaluated for their tyrosinase, acetylcholinesterase, and butyrylcholinesterase inhibitory properties. Among the examined compounds, only fomannoxin (3) displayed the antityrosinase property with 51% of inhibition, and the fungal steroids proved to be inactive. Regarding the potential acetylcholinesterase (AChE) inhibitory activity of the fungal extracts and metabolites, it was demonstrated that the chloroform extract and compounds 3–4 exerted noteworthy inhibitory activity, with 83.86 and 32.99%, respectively. The butyrylcholinesterase (BChE) inhibitory assay revealed that methanol and chloroform extracts, as well as compounds 3 and 4, exerted notable activity, while the rest of the compounds proved to be only weak enzyme inhibitors. Our study represents the first report on the chemical profile of basidiome of the wild-growing X. subpileatus, offering a thorough study on the isolation and structure determination of the most characteristic biologically active constituents of this species. [ABSTRACT FROM AUTHOR]

A catalyst‐ and solvent‐free room temperature method has been elaborated for the three‐component (carbonyl compounds, primary or secondary amines and phosphites) Kabachnik–Fields synthesis of α‐aminophosphonates. First, we have studied some parameters that potentially influence the course of the reaction using benzaldehyde, aniline and diethyl phosphite. In order to extend the reaction under the new reaction conditions, we then carried out 3 series of experiments always varying one of the three reagents. In general, with a few exceptions, good yields were obtained, although in some cases long reaction times were required. [ABSTRACT FROM AUTHOR]

Human milk oligosaccharides (HMOs) are structurally complex unconjugated glycans that are the third largest solid fraction in human milk after lactose and lipids. HMOs are in the forefront of research since they have been proven to possess beneficial health effects, especially on breast-fed neonates. Although HMO research is a trending topic nowadays, readily available analytical methods suitable for the routine investigation of HMOs are still incomplete. NMR spectroscopy provides detailed structural information that can be used to indicate subtle structural differences, particularly for isomeric carbohydrates. Herein, we propose an NMR-based method to identify the major isomeric HMOs containing GlcNAc and/or Neu5Ac building blocks utilizing their amide functionality. Experimental conditions were optimized (H2O:D2O 9:1 v/v solvent at pH 3.0) to obtain 1H-15N HSQC and 1H-15N HSQC-TOCSY NMR spectra of the aforementioned building blocks in HMOs. Four isomeric HMO pairs, LNT/LNnT, 3'SL/6'SL, LNFP II/LNFP III, and LSTa/LSTb, were investigated, and complete NMR resonance assignments were provided. In addition, 1H and 15N NMR resonances were found to be indicative of various linkages, thereby facilitating the distinction of isomeric tri-, tetra-, and pentasaccharide HMOs. The rapid growth of HMO products (from infant formulas and dietary supplements to cosmetics) undoubtedly requires expanding the range of applicable analytical methods. Thus, our work provides a 15N NMR-based method to advance this challenging field of carbohydrate analysis. [ABSTRACT FROM AUTHOR]

The 1,3-dipolar cycloaddition of 3-nitro-2(1H)-quinolones with ester-stabilized azomethine ylides derived from sarcosine ester and various aromatic aldehydes has been investigated. The structure and stereochemistry of cycloadducts were studied in detail by X-ray and NMR spectroscopy methods. [ABSTRACT FROM AUTHOR]

In the course of the synthesis of fused-ring analogues of the antidepressant drug tianeptine, representatives of three new heterocyclic ring systems, indolo[1,7- bc ][1,2]benzothiazepines (and their 4,5-dihydro analogues), 5,6-dihydroquino[1,8- bc ][1,2]benzothiazepines, and [1,2]benzothiazepino[4,3,2- jk ]carbazoles, as well as their intermediates, have been prepared. The tetracyclic and pentacyclic ring systems containing either an oxo or a hydroxy functional group are suitable for introducing various side chains, including potential pharmacophores. For this latter transformation, examples are demonstrated by conversion of the hydroxy group into a chloro moiety and subsequent reaction with amines or with primary alcohols bearing a tertiary amino side chain. Two fused-ring derivatives exhibiting the side-chain characteristics of tianeptine have also been synthesized. Altogether 40 compounds are described in the present manuscript, eight of them are also characterized by single-crystal X-ray diffraction. [ABSTRACT FROM AUTHOR]

The β-carboline core is the base structure of several biologically active natural and unnatural compounds. Herein, we report the first total synthesis of trigonostemine G, which is a newly isolated natural β-carboline alkaloid from the twigs of Trigonostemon filipes. Synthesis of two structurally close derivatives of trigonostemine G is also reported. Key step of the syntheses involves a nucleophilic addition of 5-{[tert-butyl(dimethyl) silyl]oxy}-1H-indole to 1-formyl-β-carboline building blocks. [ABSTRACT FROM AUTHOR]