Daphnezomines P, Q, R and S, new alkaloids from Daphniphyllum humile

Four new alkaloids, daphnezomines P-S (1-4), have been isolated from the fruits of Daphniphyllum humile, and the structures and the stereochemistry were elucidated on the basis of spectroscopic data including 2D NMR and MS/MS spectra, and chemical correlations. Daphnezomines P (1) and Q (2) were the first Daphniphyllum alkaloids with an iridoid glycoside moiety.     

Pheromone synthesis. Part 255: Synthesis and GC–MS analysis of pheromonal triacylglycerols of male Drosophila fruit flies

Pheromonal triacylglycerols and their analogs, 1A, 1B, 2A, 2B, 3A, 3B, and 3C, of male Drosophila fruit flies were synthesized and analyzed by GC–MS. Their GC retention times were found to be a reliable measure to analyze and identify these triacylglycerols with acetyl, oleoyl and tigloyl groups, although the stereo- and regioisomers of 1 (1A and 1B), 2 (2A and 2B), and 3 (3A, 3B, and 3C) could not be distinguished from each other by MS alone.     

Kendarimide A, a novel peptide reversing P-glycoprotein-mediated multidrug resistance in tumor cells, from a marine sponge of Haliclona sp.

A novel modulator of multidrug resistance (MDR) in tumor cells, kendarimide A (1), was isolated from an Indonesian marine sponge of Haliclona sp. Compound 1 reversed MDR in KB-C2 cells mediated by P-glycoprotein (P-gp) at a 6 μM concentration, and the chemical structure of 1 was characterized to be a linear peptide composed of N-methylpyroglutamic acid (pyroMeGlu), N-methylated eight-membered cysteinyl-cysteine (ox-[MeCys-MeCys]) together with many N-methyl amino acid residues. The amino acid sequence of 1 was determined by 2D NMR and FAB MS analysis. The absolute configuration of the amino acid residues in 1 except for the MeCys part was determined to be l-form respectively, based on interpretation of the HPLC analysis of Marfey's derivatives of the hydrolysates of 1 and the synthetic method for the pyroMeGlu residue.     

The synthesis and structural characterization of N-para-ferrocenyl benzoyl dipeptide esters: The X-ray crystal structure of N-{para-(ferrocenyl)benzoyl}-l-alanine-glycine ethyl ester

A series ofN-para-ferrocenyl benzoyl dipeptide esters 2-5 were prepared by coupling para-ferrocenyl benzoic acid (1) to the dipeptide ethyl esters using the conventional 1,3-dicyclohexylcarbodiimide (DCC), 1-hydroxybenzotriazole (HOBt) protocol. The dipeptides employed in the synthesis were Ala-Gly(OEt) (2), Ala-Ala(OEt) (3), Ala-Leu(OEt) (4) and Ala-Phe(OEt) (5). The compounds were fully characterized by a range of NMR spectroscopic techniques, electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS). In addition the X-ray crystal structure of the l-alanine-glycine derivative 2 has been determined.     

The structures of three new shishididemniols from a tunicate of the family Didemnidae

Three new serinolipid derivatives, shishididemniols C (1), D (2), and E (3), were isolated as antibacterial constituents of a tunicate of the family Didemnidae. Their planar structures were elucidated by interpretation of NMR and MS data, whereas the absolute stereochemistry was determined by chemical conversions. Shishididemniols C (3), D (4), and E (5) exhibited antibacterial activity against the fish pathogenic bacterium Vibrio anguillarum.     

Native peptide folding dominates over stereoelectronic effects of prolyl hydroxylation in loop 5 of the macrocyclic peptide kalata B1

Kalata B1 (4) is a prototypical, 29-residue, Möbius cyclotide with a cis prolyl peptide bond in loop 5. Two analogs were synthesized in which Pro²⁴ was substituted by trans-4-hydroxy-l-proline (peptide 5) and cis-4-hydroxy-l-proline (peptide 6). Linear peptides were assembled by solid phase peptide synthesis using Fmoc/tBu chemistry. Head-to-tail cyclization was performed using HATU, side-chain protecting groups removed and the cyclic peptides 2 and 3 isolated by RP-HPLC. Oxidation led to the formation of peptides 5 and 6, each incorporating three disulfide bonds. Analysis of TOCSY and NOESY spectra of the purified peptides enabled assignment of the backbone amide and Hα resonances. These showed a striking correlation with those of native kalata B1, indicating that folding had produced the same disulfide bridge topology. While somewhat surprising that stereoelectronic effects introduced by the hydroxyl substituents in this key region of the peptide had little impact, this reflects the strong thermodynamic driving force toward formation of the cyclic cystine knot scaffold.     

Isolation of key intermediates during formation of oolongtheanins

Oolongtheanin-3′-O-gallate (2b) was obtained by treatment of (−)-EGCg (1d) with CuCl₂. This transformation was achieved over three steps, with the isolation of two intermediates; their chemical structures were determined through derivatization reactions, MS, and 1D/2D NMR techniques. One intermediate was identified as dehydrotheasinensin A (3); the other was identified as the novel dimer pro-oolongtheanin-3′-O-gallate (6). Compound 3 was converted to 6 by heating in aprotic solvent, and compound 6 was converted to 2b by addition of water.     

New microviridins from a water bloom of the cyanobacterium Microcystis aeruginosa

Three new microviridins namely, SD1684 (1), SD1634 (2), and SD1652 (3), were isolated from the hydrophilic extract of Microcystis aeruginosa. The planar structures of compounds 1-3 were determined by homonuclear and inverse-heteronuclear 2D-NMR techniques as well as by high-resolution mass spectrometry. The absolute configuration of the asymmetric centers was studied using Marfey's method for HPLC. Compounds 1-3 contain l-threo-β-hydroxy aspartic acid as a building block of the peptide chain. This is the first example where microviridins contain non-proteinogenic amino acid in their structure. Compound 2 is a mild serine protease inhibitor.     

Synthesis of the first pseudo-phosphonopeptides derived from (ferrocenyl)aminomethanephosphonous acids

The first example of the condensation of (ferrocene)-N-benzhydrylamino-methanephosphonous acid (1) with α-amino acids 2a-d and several model dipeptides 4a-d and the tripeptide dl-alanyl-dl-leucinyl-glycine (4e) in the presence of DCC resulted in pseudo-phosphono-dipeptides 3a-d and pseudo-phosphono-oligopeptides 5a-d. The probable chiral assistance of the incoming amino acid or peptide in the formation of the new chiral center on phosphorus was also a feature of this method.     

Solid-phase synthesis of core 3 and core 6 O-glycan-linked glycopeptides by benzyl-protection method

Core 3 and core 6 O-glycoamino acids were prepared in a protected form suited for Fmoc solid-phase peptide synthesis (SPPS). An N-trichloroacetyllactosamine derivative (2) was used as a highly β-selective glycosyl donor in 3-O-glycosylation of acceptors 3/4 and in 6-O-glycosylation of acceptors 5/6. Zn reduction of trisaccharides 7/8 and 13/14 was followed by acetylation to readily transform trichloroacetamido and azido groups to acetamido groups. Selective deprotection by Pd(0)-catalysis afforded core 3 O-glycan building blocks 11/12 and core 6 O-glycan building blocks 17/18. Usefulness of these building blocks for SPPS was demonstrated by the syntheses of the core 3-linked MUC2 tandem repeat glycopeptide and the core 6-linked glycopeptide segment of MUC6. The synthetic glycopeptides detached from the resin were debenzylated under the ‘low-acidity TfOH’ conditions.     

Six insecticidal isoryanodane diterpenoids from the bark and twigs of Itoa orientalis

Four rare isoryanodane diterpenoids namely itols A-D (1-4) and two isoryanodane glucosides (5 and 6) were isolated from the bark and twigs of Itoa orientalis. Their structures were determined by NMR and MS techniques and the structure of 1 was confirmed by a single-crystal X-ray diffraction. These six diterpenoids obviously showed insecticidal activity against Spodoptera exigua, with LC₅₀ 28.62 ppm for 1 and 52.76 ppm for 2, respectively. In anti-inflammatory assay, compounds 1 and 4-6 showed anti-COX-2 activity, with inhibitory rates of 54.7-78.3% at 10 μM.     

Palladium-catalyzed oxyarylation of olefins using silver carbonate as the base. Probing the mechanism by electrospray ionization mass spectrometry

The Pd(OAc)₂-catalyzed oxyarylation of electron-rich (8 and 12) and electron-poor (10) olefins by ortho-iodophenols (3a-d) was studied using Ag₂CO₃ as the base, in acetone, and in the presence and absence of PPh₃. The corresponding adducts of oxyarylation were obtained in moderate yields. The reaction mechanism was examined by electrospray ionization mass spectrometry (ESI-MS). Cationic arylpalladium intermediate (14), formed by the oxidative insertion of Pd(0) into 3a, and the cationic palladacycles (15), obtained by reaction of 14 with olefins 8 and 12, were intercepted by ESI-MS and characterized by ESI-MS/MS.     

Highly stereoselective synthesis of novel trans-thiophenylene-silylene-vinylene-arylene molecular and macromolecular compounds

Novel stereoregular molecular compounds 8-13 containing thiophenylene-silylene-vinylene-phenylene units have been synthesised via highly effective silylative coupling of styrene and 1,4-divinylbenzene (7) with respective vinylsilylthiophenes (3, 4) and bis(vinylsilyl)thiophenes (5, 6) catalyzed by RuHClCO(PCy₃)₂. Respective copolymers (14, 15) were produced via silylative copolycondensation of 5 and 6 with 7. All products were isolated and characterised by NMR, MS, HRMS and two of them 10 and 11 by X-ray method. Catalytic study as well as stoichiometric reactions of Ru-H (1) with 2-(vinylsilyl)thiophene (3) and Ru-Si (16) with styrene confirmed the mechanism of the silylative coupling olefins with vinylsilicon compounds.     

Synthesis of functional Δ-1,3,5-oxazaphospholene and 2H-1,4,2-diazaphosphole complexes via catalytic ring expansion reactions of a 2H-azaphosphirene complex

Catalytically-induced ring expansion of 2H-azaphosphirene complex 1 using ferrocenium hexafluorophosphate and acetone (2), diethylketone (3), cyclohexanone (4), benzaldehyde (5) or para-hydroxy-benzaldehyde (6) furnished selectively the Δ³-1,3,5-oxazaphospholene complexes 7-11, whereas with ortho- and para-hydroxy- or ortho- and para-amino-substituted benzonitriles the 2H-1,4,2-diazaphosphole complexes 16-19 were obtained. Two further findings are noteworthy: (1) The significant decreased reaction time in the case of the sterically more demanding carbonyl derivatives 2-4 and (2) the formation of diastereomers in the case of 10 and 11 with a ratio of 8:1 and 9:1, respectively. All products were characterized by NMR, MS and elemental analysis and the configuration of complexes 7 and 10a were determined by X-ray single-crystal diffraction analysis.     

Structure elucidation of EI-1941-1 and -2, novel interleukin-1β converting enzyme inhibitors produced by Farrowia sp. E-1941

EI-1941-1 (1a) and EI-1941-2 (2a) accompanied by EI-1941-3 (3) have been isolated from culture broth of Farrowia sp. E-1941 as the inhibitors of interleukin-1β converting enzyme. The structures of 1a, 2a, and 3 were elucidated by the analysis of NMR and MS data, and finally the absolute stereochemistries of 1a and 2a were confirmed by optical rotation data, or X-ray crystallographic analysis of p-bromobenzoate, 2b, respectively.     

The synthesis, spectroscopic properties and X-ray structure of Zn(II) complexes with amino derivatives of chromone

Three new Zn(II) complexes containing the ligands 5-amino-8-methyl-4H-chromen-4-one (1), 6- or 7-amino-2-phenyl-4H-chromen-4-one (2, 3) were prepared. The new synthesised compounds were characterised by IR, ¹H NMR and MS spectroscopy. The crystal structure of complex 4 was determined with the use X-ray diffraction. The Zn(II) centre of 4 is linked by two chlorido and two N-bound aminochromone ligands, 1, in a strongly distorted tetrahedral configuration with the dissymetric point group C₂. The protonation constants of the ligands 1, 2 and 3 corresponded to 3.68, 3.88 and 6.83, respectively. The stability constants of the Zn(II) complexes were calculated from the potentiometric titration data. The complexes were found to have the formulae ML and ML₂ for ligands 1 and 2, and ML for ligand 3. Fluorescence spectroscopic properties were also studied; the strongest fluorescence in solution was exhibited by complex 6.     

Aplyronine A, a potent antitumor macrolide of marine origin, and the congeners aplyronines B and C: isolation, structures, and bioactivities

Aplyronine A (2), a potent antitumor macrolide was isolated from the sea hare Aplysia kurodai together with the congeners aplyronines B (3) and C (4). The absolute stereostructure of aplyronine A (2) was determined by the instrumental analysis (mainly NMR and MS) and the enantioselective synthesis of the fragments obtained from chemical degradation of aplyronine A (2). The structures of aplyronines B (3) and C (4) were also elucidated. Cytotoxicity and antitumor activity of aplyronine A (2) were evaluated.     

Proanthocyanidin glycosides from the leaves of Quercus ilex L. (Fagaceae)

From the polar extracts of the leaves of Quercus ilex L., two new proanthocyanidin glycosides, namely afzelechin-(4α→8)-catechin-3-O-β-glucopyranoside (1) and afzelechin-(4α→8)-catechin-3-O-α-rhamnopyranoside (2), were isolated in addition to catechin (3), proanthocyanidin B₃ (4), prodelphinidin C (5), dehydrodicatechin A (6), quercetin (7) and six known flavonol glucosides with their acylated derivatives (8-13) and ellagic acid (14). The structures of all isolated compounds were established by spectroscopic means, mainly 1D and 2D NMR, as well as LC/MS and HR-MS spectrometric analyses. The absolute configuration of compound 1 was determined by CD measurements. The proanthocyanidin glycosides are especially interesting, as they possess the sugar in the upper unit of the dimer, which is rare for this type of compounds.     

New polyesters from Talaromyces flavus

Six new polyesters, talapolyesters A–F (1–4, 14, and 16), together with 11 known ones 15G256ν (5), 15G256ν-me (6), 15G256π (7), 15G256β-2 (8), 15G256α-2 (9), 15G256α-2-me (10), 15G256ι (11), 15G256β (12), 15G256α (13), 15G256α-1 (15), and 15G256ω (17), were isolated from the wetland soil-derived fungus Talaromyces flavus BYD07-13, and their structures were determined by NMR and MS spectroscopic data. Among them, 1–4 and 16 were assembled in a different manner from that of the known 256 polyesters. All the polyesters are composed of (R)-2,4-dihydroxy-6-(2-hydroxypropyl)benzoic acid and (R)-3-hydroxybutyric acid/(S)-3,4-dihydroxybutyric acid residues. The absolute configurations of the residues were determined by alkaline hydrolysis. The cytotoxicity against five tumor cell lines of these compounds was examined, and a tight structure–activity relationship is proposed.     

Nucleation of the β-hairpin structure in a linear hybrid peptide containing α-, β- and γ-amino acids

Synthesis and conformational studies of a short linear peptide containing a pyrrole amino acid (1, Paa) and a furan amino acid (2, Faa), namely Boc-hGly-Faa-d-Pro-Gly-Paa-hGly-Faa-OMe (3), were carried out in which it was established that peptide 3 adopted a well-defined β-hairpin structure in DMSO-d₆.