Structure and Biosynthesis of Xenoamicins from Entomopathogenic Xenorhabdus

During the search for novel natural products from entomopathogenic Xenorhabdus doucetiae DSM17909 and X. mauleonii DSM17908 novel peptides named xenoamicins were identified in addition to the already known antibiotics xenocoumacin and xenorhabdin. Xenoamicins are acylated tridecadepsipeptides consisting of mainly hydrophobic amino acids. The main derivative xenoamicin A ( 1 ) was isolated from X. mauleonii DSM17908, and its structure elucidated by detailed 1 D and 2 D NMR experiments. Detailed MS experiments, also in combination with labeling experiments, confirmed the determined structure and allowed structure elucidation of additional derivatives. Moreover, the xenoamicin biosynthesis gene cluster was identified and analyzed in X. doucetiae DSM17909, and its participation in xenoamicin biosynthesis was confirmed by mutagenesis. Advanced Marfey’s analysis of 1 showed that the absolute configuration of the amino acids is in agreement with the predicted stereochemistry deduced from the nonribosomal peptide synthetase XabABCD. Biological testing revealed activity of 1 against Plasmodium falciparum and other neglected tropical diseases but no antibacterial activity.     

Cohirsine - a novel isoquinolone alkaloid from

A novel alkaloid, cohirsine (1) was isolated from . Its structure has been investigated by extensive NMR studies including 2D NMR experiments. Its stereochemistry has been determined by 2D NOESY and NOE difference measurements.     

Chloramultilide A, a highly complex sesquiterpenoid dimmer from Chloranthus multistachys

A highly complex sesquiterpenoid dimmer, chloramultilide A (1), was isolated from Chloranthus multistachys. Its structure and relative stereochemistry were mainly established by using 1D NMR and 2D NMR spectra.     

Bishyoscyamine, one unusual dimeric tropane alkaloid from Anisodus acutangulus

One unusual dimeric tropane alkaloid, bishyoscyamine, was isolated from the roots of Anisodus acutangulus, whose structure including the absolute stereochemistry was unambiguously determined based on extensive 1D NMR and 2D NMR, HR-ESI-MS [α]D and CD spectroscopic analyses. To our knowledge, bishyoscyamine is the first example of tropane alkaloid dimer condensed by a C-N bond.     

青蒿素及其类似物的结构和合成 VIII:^1H核磁共振测定青蒿素降解物及有关化合物的构型

The present report deals with the stereochemistry of the degradation products of arteannuin and some intermediates of its total synthesis. The configurations of 13-CH3 and lactone ring are deduced by using spin-spin coupling constants and the pattern of 11-H as well as the NOE results from 1H NMR spectroscopy.     

A novel secondary metabolite of Chinese ted alga Laurencia karlae

A novel skeleton compound benkarlaol (1) was isolated from the red alga Laurencia karlae Zhang et Xia, collected from the Nansha Islands in the South China Sea. Its structure and relative stereochemistry were determined by spectroscopic data, especially extensive 1D and 2D NMR experiments.     

Resveratrol Tetramers from the Roots of Ampelopsis sinica

Various biological activities of stilbenoids have been described, such as antifungal and antibacterial activities1, antihepatotoxic activity2-4, anti-HIV activity5. Stilbenoids mainly existed in Vitaceae, Diperocarpaceae, Gnetaceae, Cyperaceae, Leguminase1. Many oligostilbenes have been isolated from Vitaceaeous plants. But, there was no report on the stilbenoids in Ampelopsis sinica (Miq.) W. T. Wang which was traditionari- ly used to treat arthritis6. In our study on the constituen…     

(+)-Apollineanin: a new flavanone from Tephrosia apollinea

Chemical investigation of the leaves of Tephrosia apollinea has yielded a new flavanone named (+)-apollineanin, together with two known flavones: (-)-semiglabrin and (-)-semiglabrinol. The structure of the new compound was determined on the basis of mass, 1D and 2D NMR spectroscopies including NOE difference spectroscopy. The absolute stereochemistry of (+)-apollineanin was determined by Mosher ester methodology and from CD data.     

Structure and stereochemistry of a new cytotoxic polychlorinated sulfolipid from Adriatic shellfish

A detailed analysis of the causative toxins contained in the hepatopancreas of toxic mussels from the northern Adriatic sea has been carried out. Along with some DSP (diarrhetic shellfish poisoning) type toxins, such as okadaic acid, yessotoxin, and their derivatives, which are involved in a number of human intoxications throughout the world, we have now isolated a new cytotoxin, a polychlorinated sulfolipid 1, whose gross structure has been elucidated by spectral analysis, including various 2D NMR techniques. The relative stereochemistry of 1 was elucidated by successful application of the J-based configuration analysis developed for acyclic compounds using carbon-proton spin-coupling constants ((2,3)J(C,H)) and proton-proton spin-coupling constants ((3)J(H,H)); its absolute stereochemistry was established by the Mosher method. Compound 1 possesses in vitro cytotoxicity against WEHI 164 and RAW 264.7 cells.     

Competitive stereochemical control operative during conrotatory electrocyclization of helically equilibrating diquinanyl-substituted 1,3,5,7-octatetraenyl bisenolates

[Carbohydrate structure: see text] Activation of the squarate ester cascade by adding the lithiated bicyclo[3.3.0]octene 20 and vinyllithium sequentially to 1 results in the isolation of the four tetracyclic products 21-24. The structures of the topographically complex products were deduced by 2D NMR spectroscopy and X-ray diffraction studies. The mechanistic insights gained by these findings are discussed. The product distribution is telltale evidence for predominant 1,2-addition of the second alkenyl anion. Product stereochemistry is in turn diagnostic of the preferred mode of conrotatory ring closure operating within equilibrating helical intermediates of opposite pitch. A competing pathway for the elimination of methanol in these highly functionalized intermediates has been observed for the first time.     

A novel heptacyclic diterpene from Alpinia pahangensis Ridley,a wild ginger endemic to Malaysia

Pahangensin D (1), a bis-labdanic diterpene featuring an unprecedented carbon skeleton, was isolated as a minor constituent from the rhizomes of Alpinia pahangensis Ridley. Its structure and relative stereochemistry were established on the basis of rigorous spectroscopic methods including 1D and 2D NMR techniques and LCMS-IT-TOF analysis.     

Lancifodilactone A, a novel bisnortriterpenoid from Schisandra lancifolia

A novel bisnortriterpenoid, lancifodilactone A, has been isolated from the leaves and stems of Schisandra lancifolia. Its structure and stereochemistry were determined primarily from 1D and 2D NMR spectroscopic data, and were confirmed by a single crystal X-ray analysis.     

Amphidinolide T, novel 19-membered macrolide from marine dinoflagellate Amphidinium sp

A novel 19-membered macrolide, amphidinolide T (1), has been isolated from a marine dinoflagellate Amphidinium sp., and the structure was elucidated on the basis of spectroscopic data. Relative stereochemistry at C-7, C-8, and C-10 was deduced from the NOESY correlations, while absolute configurations at C-2, C-13, C-14, and C-18 were assigned on the basis of NMR data of the MTPA esters of 1 and those of degradation products of 1.     

Structure and absolute stereochemistry of phormidolide,a new toxic metabolite from the marine cyanobacterium Phormidium sp

The extract from a laboratory culture of an Indonesian isolate of the cyanobacterium Phormidium sp. displayed inhibitory activity in a Ras-Raf protein interaction assay. Assay-guided fractionation led to the isolation of both active and inactive materials of novel structure. The major inactive metabolite, phormidolide, was nevertheless highly toxic to brine shrimp (LC(50) = 1.5 microM), and hence, its structure was elucidated using various spectroscopic methods, primarily NMR. A series of partial structures were developed from standard experiments and then assembled using GHMBC, 2D INADEQUATE, and ACCORD-ADEQUATE data obtained on a (13)C-enriched sample. The relative stereochemistry at phormidolide's 11 chiral centers was established using the J-based configuration analysis method in concert with the G-BIRD(R)-HSQMBC NMR experiment. Absolute stereochemistry was determined on a bis-acetonide derivative using the variable temperature Mosher ester method. The robust number of NMR restraints provided from determination of most homonuclear and heteronuclear coupling constants in phormidolide, along with an abundance of NOE information, allowed construction of a refined lowest energy three-dimensional structure in Macromodel. Phormidolide is one of only a few macrolide-type natural products to be reported from marine cyanobacteria.     

A new cyclopeptide alkaloid from the bark of waltheria douradinha

Waltherine-C (5), a novel 14-membered cyclopeptide alkaloid has been isolated, together with four known cyclopeptide alkaloids, waltherine-A (1) and -B (2), scutianine-B (3) and adouetine-Y' (4), from the bark of Waltheria douradinha (Sterculiaceae) from Rio Grande do Sul, Brazil. The structure and NMR assignments of this new alkaloid were determined by 1D and 2D NMR techniques. The stereochemistry of the ring amino acid residue and the N,N-dimethyl amino acid side-chain has been assigned by gas chromatography employing modified cyclodextrins as chiral stationary phases.     

Sagittamides A and B. Polyacetoxy long-chain acyl amino acids from a didemnid ascidian

[structure: see text]. An unidentified tunicate from Pohnpei, Micronesia, yielded sagittamides A and B-compounds comprising a long-chain C26 dicarboxylic acid that acylates terminal L-valine and L-ornithine groups. The structures, which contain an unprecedented internal O-hexacetyl-1,2,3,4,5,6-hexaol moiety, were determined by combined spectroscopic analysis including mass spectrometry and 1D and 2D NMR and chemical degradation. The partial absolute stereochemistry of the new compounds was addressed by Marfey's analysis.     

Relative and absolute stereochemistry of secondary/secondary diols: low-temperature 1H NMR of their bis-MPA esters

Comparison of the room- and low-temperature 1H NMR spectra of the bis-(R)- or bis-(S)-MPA ester derivative of an open chain sec,sec-1,2-diol allows the easy determination of its relative stereochemistry and in some cases absolute configuration. If the diol is anti, its absolute configuration can be directly deduced from the signs of DeltadeltaT1T2 for substituents R1/R2, but if the relative stereochemistry of the diol is syn, the assignment of its absolute configuration requires the preparation of two derivatives (both the bis-(R)- and bis-(S)-MPA esters), comparison of their room-temperature 1H NMR spectra, and calculation of the DeltadeltaRS signs for the methines Halpha(R1) and Halpha(R2) and R1/R2 protons. The reliability of these correlations is validated with 17 diols of known absolute configuration used as model compounds.     

Structure-based predictions of H NMR chemical shifts of sesquiterpene lactones using neural networks

In this work the prediction of ¹H NMR chemical shifts of CH_n protons of sesquiterpene lactones by means of neural networks is described. This method is based on the incorporation of experimental chemical shifts of protons of sesquiterpene lactones as additional memory of an associative neural network system previously trained with chemical shifts of other organic compounds. One advantage of this method is its ability to distinguish between CH₂ diastereotopic protons belonging to rigid substructures since stereochemistry is considered. This is achieved via the automatic conversion of the 2D structure diagram into a 3D molecular structure. The predicted ¹H NMR chemical shifts of the sesquiterpene lactones showed a high level of accuracy. This is the first report on a fully automatic proton assignment of structures of sesquiterpene lactones of an accuracy that allows its use in structure elucidation.     

Sieboldine A, a novel tetracyclic alkaloid from Lycopodium sieboldii, inhibiting acetylcholinesterase

[structure: see text] A novel Lycopodium alkaloid with an unprecedented fused-tetracyclic ring system consisting of an aza-cyclononane ring having a N-hydroxy group, a cyclohexanone, a cyclopentanone, and a tetrahydrofuran ring, sieboldine A (1), was isolated from the club moss Lycopodium sieboldii. The structure and relative stereochemistry were elucidated on the basis of 2D NMR data and X-ray analysis. Sieboldine A (1) exhibited a potent inhibitory activity against acetylcholinesterase and modest cytotoxicity.     

Cytotoxic fatty acid from Pleurocybella porrigens

The new conjugated ketonic fatty acid, porrigenic acid (1), was isolated as a cytotoxic constituent of Pleurocybella porrigens. The structure of 1 was elucidated using spectroscopic methods including 1D and 2D NMR and MS. The absolute stereochemistry of 1 was determined by application of the exciton chirality method. Compound 1 exhibited cytotoxic activity against myeloma THP-1 cells, but did not show any significant toxicity against B16F1 melanoma. This is the first report of the isolation and structural elucidation of the new cytotoxic constituent porrigenic acid (1) from the edible mushroom P. porrigens.