Mycopyranone: A 8,8ˈ-binaphthopyranone with potent anti-MRSA activity from the fungus Phialemoniopsis sp.

A new 8,8?-binaphthopyranone (mycopyranone, 1) was isolated from a solid fermentation of Phialemoniopsis sp. (fungal strain MSX61662), and the structure was elucidated via analysis of the NMR and HRESIMS data. The axial chirality of 1 was determined to be M by ECD. The central chirality at C-4/C-4? was assigned through a modified Mosher’s method, while the absolute configuration at C-3/C-3? was deduced based on analysis of the ³J_H-3-H-4 values and NOESY correlations. Compound 1 was evaluated for its antimicrobial properties against Staphylococcus aureus SA1199 and a clinically relevant methicillin-resistant S. aureus strain (MRSA USA300 LAC strain AH1263). Compound 1 inhibited the growth of both strains in a concentration dependent manner with IC₅₀ values in the low μM range. Molecular docking indicated that compound 1 binds to the FtsZ (tubulin-like) protein in the same pocket as viriditoxin (2), suggesting that 1 targets bacterial cell division.     

Synthesis and stereochemistry of highly crowded N-benzylpiperidones

A series of N-benzylated 3,5-diakyl-2,6-diarylpiperidin-4-ones 4–8 were conveniently synthesized in significant yields of 68–88% by N-benzylation of the corresponding 2,6-diaryl-3,5-dimethylpiperidin-4-ones 1–3 using different benzyl bromides. Initially, the new piperidone 2,6-bis(4-ethoxyphenyl)-3,5-dimethylpiperidin-4-one 3 was synthesized by the condensation of 1:1:2 M ratio of 3-pentanone, ammonium acetate and para-ethoxybenzaldehyde in ethanolic medium. All the synthesized new compounds 3–8 were characterized by their analytical and spectral (IR, ¹H and ¹³C NMR) interpretations. The stereochemistry of the new piperidone 3 was elucidated as chair conformation with an equatorial orientation of all substituents, suggested by its vicinal couplings from ¹H NMR spectrum. To investigate the impact on piperidone stereochemistry as well as NMR chemical shifts, all the N-benzylated products 4–8 were compared with their corresponding precursors, and as a result, it is clearly established that all the synthesized N-benzyl piperidones exist in the chair conformation with an equatorial orientation of all the substituents at C-2, C-3, C-5, C-6 and N. Contrary to the probability all N-benzylated compounds retain the same conformation and configuration as their precursors, however, a remarkable change on the chemical shifts are observed. For the further unambiguous confirmation of stereochemistry, the 1-benzyl-3,5-dimethyl-2,6-diphenylpiperidin-4-one 4 was examined by single-crystal X-ray diffraction. The compound 4, C₂₆H₂₇NO, crystallized in a P-1 space group under triclinic system with unit cell dimensions a, b, c (Å) and α, β, γ (°) of 10.156(2), 11.002(2), 11.348(4) and 116.74(4), 100.81(3), 100.17(3), respectively.     

Xylomexicanins E-H,new limonoids from Xylocarpus granatum

Four novel tetranortriterpenoids, xylomexicanins E–H (1–4), were isolated from the seeds of the Chinese mangrove, Xylocarpus granatum. Among them, xylomexicanin E (1) represents the first example of limonoid with azaspiro skeleton between B (pyrrolidine) and C rings, whose biosynthetic pathways were proposed. The structures were elucidated on the basis of one- and two-dimensional NMR (including ¹H, ¹³C NMR, DEPT, ¹H–¹H COSY, HSQC, HMBC, and NOESY) and confirmed by high-resolution mass spectrometry. Compound 2, the second example of a limonoid with a C-9–C-30 linkage, showed moderate activity against the A549 and RERF cell line with IC₅₀ value of 18.83 and 15.83 μM,     

Saxifraganoids A and B,two novel cucurbitane triterpenoid glycosides from Saxifraga umbellulata var. pectinata

Two novel cucurbitane triterpenoid glycosides, named saxifraganoids A (1) and B (2), were isolated from Saxifraga umbellulata var. pectinata. Their structures including absolute configurations were elucidated based on the analysis of spectroscopic data (1D, 2D NMR and HRMS), and single-crystal X-ray diffraction. Compound 1 represents the first example of cucurbitane triterpenoid with a Δ¹⁷⁽²⁰⁾, and compound 2 contained an unusual N-acetylglucosamine at C-16. The protective effects against liver injury induced by carbon tetrachloride (CCl₄) in the human embryonic-liver L-02 cells of these two compounds were evaluated.     

New cytotoxic halogenated sesquiterpenes from the Egyptian sea hare, Aplysia oculifera

Two new sesquiterpenes, oculiferane (1) and epi-obtusane (2) have been isolated and identified from an acetone extract of the digestive gland of the sea hare, Aplysia oculifera. The structures were elucidated by spectroscopic analysis including HREIMS, ¹H, ¹³C, DEPT, ¹H–¹H COSY, HMQC, and HMBC NMR; the relative configuration was confirmed by X-ray analysis. Compounds 1 and 2 exhibited cytotoxic activity in vitro against several human cancer cell lines with IC₅₀ values in the low μg/ml range.     

Artanomadimers A–F: six new dimeric guaianolides from Artemisia anomala

A novel dimeric guaianolide with an unprecedented skeleton, named artanomadimer A (1), and five new analogues, artanomadimers B–F (2–6), were isolated from the aerial parts of Artemisia anomala. Their structures and stereochemistry were elucidated by extensive spectroscopic methods, and the absolute stereochemistry of compound 4 was confirmed by X-ray crystallographic analysis. Artanomadimer A (1) is probably formed through a Diels–Alder reaction with the new carbon–carbon bond formation of C-11/C-2′ and C-13/C-5′ based on its structure. A cytotoxic evaluation showed that compounds 1 and 6 exhibited significant inhibitory effects against the cell growth of BGC-823 tumor cell lines with IC₅₀ values of 2.71 and 6.25 μM, respectively.     

A novel norsesquiterpene alkaloid from the mushroom-forming fungus Flammulina velutipes

A new norsesquiterpe alkaloid（1） was isolated from the solid culture of mushroom-forming fungus Flammulina velutipes fermented on rice.The structure of 1 was elucidated by spectroscopic methods.The absolute configuration of C-1 in 1 was determined using the circular dichroism data of their [Rh₂（OCOCF₃）₄]complex.     

Didemnaketals D and E,bioactive terpenoids from a Red Sea ascidian Didemnum species

Two new spiroketals, didemnaketals D (1) and E (2) were isolated from a marine ascidian species belonging to the genus Didemnum. The structures of the compounds were elucidated by extensive 1D (¹H, ¹³C, and DEPT) and 2D (COSY, TOCSY, HSQC, HMBC, NOESY, and ROESY) NMR studies and high-resolution mass spectroscopic data. The new didemnaketals differ from the reported ones in which that they lack the methyl functionality at C-6 and the hydroxy moiety at C-21. Instead, they possess an ester moiety at C-6 in addition to new oxygen functionality at C-20 of the didemnaketals. Compounds 1 and 2 were evaluated for their protein kinase inhibitory activity against different kinases (CDK5, CK1, DyrK1A, and GSK3) at 10 μg/mL. Compounds 1 and 2 showed moderate activity against these kinases. In addition, the compounds displayed moderate antimicrobial activity against Staphylococcus aureus and Bacillus subtilis, respectively.     

H NMR aided elucidation of products derived from photodegradation of ethyl 3-azido-4,6-difluorobenzoate in 2,2,2-trifluoroethanol

The major products formed upon photolysis of ethyl 3-azido-4,6-difluorobenzoate in 2,2,2-trifluoroethanol-d₃ has been elucidated by ¹H NMR analysis of the product mixture. Among the products formed and structurally elucidated was a hitherto unreported product formed during photolysis of aryl azides, namely azoxybenzene 19. The structural assignments of the major components of the reaction mixture were aided by comparison with ¹H NMR data from synthetic reference materials and compound isolation. MS, MS/MS, and HPLC analysis as well as UV spectroscopy was also employed in order to confirm and aid the structural analysis.     

New compounds from the roots of Coriaria nepalensis

One new sesquiterpene lactone possessing novel variations in the structure, corialactone E (1), one new neolignan, coriarianeolignan A (2), together with three known apocarotenoids (3-5) and one known neolignan (6), have been isolated from a CHCl₃ extract of the roots of Coriaria nepalensis.     

Oxidation of vanillins with thallium(III) nitrate. An exercise in NMR spectroscopy and photochemistry

Oxidation of isovanillin, vanillin and o-vanillin with TI(NO₃)₃ in MeOH gave the dimethyl acetals of 6,6-dimethoxy-2,4-cyclohexadien-1-one aldehydes (4–6 which dimerized spontaneously to give a single product each (7–9) the structure of which was elucidated by ¹H and ¹³C NMR, photocyclization to the cage compounds 12–14 and of 7 and 9 by X-ray diffraction as well.     

Alkaloids of NIRAM,natural dye from Polygonum tinctorium,and their anti-inflammatory activities

Phytochemical investigation of EtOH extract of NIRAM, natural dye from Polygonum tinctorium, resulted in the purification of nine alkaloid compounds (1–9) including four new compounds (1–4). Structures of these new compounds were elucidated by 1D and 2D NMR (¹H and ¹³C NMR, ¹H–¹H COSY, ¹H–¹³C HSQC, ¹H–¹³C HMBC), IR, UV, HR-ESI-MS, and ECD spectra. Isolated compounds (1–9) were tested for their inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-activated BV-2 cells. Compounds 1–3, 5, and 7 showed potent NO production inhibitory activities, with IC₅₀ values of 3.88–22.87 μM.     

Aufkl?rung der 1H- und 13C-NMR-spektren sowie der kristallstruktur unges?ttigter glycosylphosphonate und konformationsberechnungen an modellen1

By application of a modified LAOCN-3 program a complete elucidation of the ¹H NMR spectra of 2,3-unsaturated glycosyl phosphonates 1–5 could be achieved. The exactly determined ⁿJ(H, H) and novel ⁿJ(C, P) coupling constants are discussed, and permit a conclusive deduction of the conformations. The ¹³C NMR spectra of 1 to 6 can be fully interpreted. By a close inspection of chemical shifts as well as ¹J(C-H) and ⁿJ(C, P) coupling constants the conformational assignment is supported. For all the derivatives the correlations ¹J(C-1,H_e)>¹J(C-1, H_a) and ¹J(C-1, P_e) >¹J(C-1, P_a) can be used for the assignment of anomers. The crystal structure of 1 is in accordance with this assignment of anomers and displays an unexpected conformation. Calculations by MINDO-3 in resembling model compounds serve to elucidate such conformative effects.     

Lycocasuarines A–C,Lycopodium alkaloids from Lycopodiastrum casuarinoides

Three lycodine-type Lycopodium alkaloids (1–3) were isolated from Lycopodiastrum casuarinoides. Their structures were elucidated by spectroscopic analysis, single-crystal X-ray crystallography, and computational methods. Compound 1 possesses a rearranged five-membered ring D resulting from C-8/C-15 cleavage and a new C-7/C-15 linkage. Compound 2 is the first Lycopodium alkaloid found to bear an additional carbon (C-17) directly bonded to C-8, which is particularly unusual from a biogenetic point of view. Compounds 1–3 were evaluated for acetylcholinesterase inhibitory activities.     

Two new cycloartanes from the leaves of Combretum quadrangulare growing in Vietnam and their biological activities

Two new cycloartanes, combretanones G and H (1 and 2), were isolated from the leaves of Combretum quadrangulare. Their structures were elucidated by applying a set of spectroscopic methods, while their relative configurations were determined using DFT-NMR chemical shift calculations and subsequent assignment of DP4 probabilities. Compounds 1 and 2 are C-23/C-24 stereoisomers of the previously-reported euphonerin E. Both exhibited moderate cytotoxicity against three human cancer cell lines. Compound 2 was shown to be a potent antiparasitic. Our results confirm the traditional medicinal uses of Combretum quadrangulare in Vietnam.     

A rearranged seco-steroid with new skeleton and five new abnormal progesteroids from Nodulisporium sp.

Abeo-nodulisporisteroid A (1), an abnormal steroid with a rearranged C3 chain at C-9 possibly derived from seco-ring A via Wagner-Meerwein rearrangement and oxidations, was obtained from Nodulisporium sp. together with five related new seco-progesteroids (nodulisporisteroids M-Q, 2–6), which were elucidated by the extensive spectroscopic analysis and X-ray crystallography. A plausible biosynthetic pathway of 1–6 was also proposed. Furthermore, these isolated compounds were also evaluated for cytotoxicities against five human tumour cell lines, antimicrobial activities, and inhibitions against PI3K gamma, Aβ₄₂ aggregation, and α-glucosidase.     

Sterols from the brown alga Cystoseira foeniculacea: Degradation of fucosterol into saringosterol epimers

The present study was carried out in order to determine the phytochemical composition of the marine brown alga Cystoseira foeniculacea collected off the coasts of Algeria. After a preliminary fractionation of its organic crude extracts by column chromatography, the resulting fractions were further analysed by ¹H NMR. Even though algal species of the genus Cystoseira are commonly known to produce a wide variety of meroditerpenoids, in the case of C. foeniculacea none of the fractions were found to contain such compounds: most of the fractions showed typical ¹H NMR signals of fatty acids and derivatives (mainly glycerolipids and glycolipids). Nevertheless, the thorough analysis of a sterol-enriched fraction by RP-C₈ HPLC led to the isolation, for the first time from this species, of fucosterol (1) and a mixture of saringosterols (2 and 3). The NMR data of compounds 1–3 were fully determined with the help of 1D and 2D experiments which allowed the reassignment of some attributions in comparison with those reported in the literature. This work also confirms evidence of the oxidative degradation of fucosterol into a C-24 epimeric mixture of saringosterols.     

Mechanism of the “abnormal” pyrolytic 1,3-elimination of 2-adamantyl methane sulphonate

Pyrolysis of syn-2-adamantyl-4-d₁ methane-sulphonate 8 in a silanised pyrex reactor leads to protoadamantene with about 0.25 atoms ²H at each of C-2, -7 and -9 and little labelling elsewhere according to ²H and ¹³C NMR. This indicates complete epimerisation of 8 before elimination. In the concurrently formed dehydroadamantane, unequal partitioning of label between positions C-6/8, -9 and -10 suggests only limited epimerisation before elimination. Pyrolysis of the 4,4-dideuteriated sulphonate 11, gave analogous results. The syntheses of 8 and 11 are described and the relevance of the analytical results to possible mechanisms is considered.     

A modular design of ruthenium(II) catalysts with chiral C2-symmetric phosphinite ligands for effective asymmetric transfer hydrogenation of aromatic ketones

Hydrogen-transfer reduction processes are attracting increasing interest from synthetic chemists in view of their operational simplicity. The new chiral C₂-symmetric ligands N,N′-bis-[(1S)-1-sec-butyl-2-O-(diphenylphosphinite)ethyl]ethanediamide, 1 and N,N′-bis-[(1S)-1-phenyl-2-O-(diphenylphosphinite)ethyl]ethanediamide, 2 and the corresponding ruthenium complexes 3 and 4 have been prepared and their structures have been elucidated by a combination of multi-nuclear NMR spectroscopy, IR spectroscopy, and elemental analysis. ¹H–³¹P NMR, DEPT, ¹H–¹³C HETCOR, or ¹H–¹H COSY correlation experiments were used to confirm the spectral assignments. The catalytic activity of complexes 3 and 4 in transfer hydrogenation of acetophenone derivatives by iso-PrOH has also been studied. Under optimized conditions, these chiral ruthenium complexes serve as catalyst precursors for the asymmetric transfer hydrogenation of acetophenone derivatives in iso-PrOH and act as excellent catalysts, giving the corresponding chiral alcohols in 99% yield and up to 75% ee. This transfer hydrogenation is characterized by low reversibility under these conditions.     

Stereoselective synthesis of novel C-3 functionalized 3-sulfonyl-β-lactams: Promising biologically active heterocyclic scaffolds

An efficient and operationally simple strategy for the stereoselective synthesis of novel C-3 functionalized 3-sulfonyl-β-lactam heterocycles is described. The C-3 functionalized 3-phenyl/benzylsulfonyl-β-lactams 3/3′, 5/5′ has been synthesized via Michael addition using different Michael acceptors on trans-3-phenyl/benzylsulfonyl-β-lactams 2(a–f) using K₂CO₃ as a base and acetonitrile/DMF as solvents. The reaction furnished exclusively cis-β-lactam adducts 3(a–r) using sterically less hindered Michael acceptors. Further, the effect of steric bulk and chiralilty of Michael acceptors was explored to achieve target C-3 functionalized β-lactams 3(s-u)/3′(s-u) and 5(a–c)/5′(a–c). The structural and stereochemical analysis of novel β-lactams were carried out using FT-IR, NMR (¹H, ¹³C, ¹H-¹H COSY, ¹H-¹³C COSY and ¹³C DEPT-135), elemental analysis (CHNS), mass spectrometry (EIMS and LCMS) in representative cases and single crystal X-ray crystallographic studies (3e). The cis or trans configuration of the Michael acceptor (E) at C-3 was assigned with respect to C4-H.