Alkaloids of Uncaria attenuata,U. orientalis and U. Canescens

3-Iso-19-epi-ajmalicine, epiallo-corynantheine and dihydrocorynantheine pseudoindoxyl, not previously known as natural products, have been isolated from samples of U. attenuata. Akuammigine, dihydrocorynantheine, hirsutine, hirsuteine, mitraphylline, speciophylline, uncarines A and B, isorhynchophylline rhynchophylline, isocorynoxeine, corynoxeine, corynoxine B, rotundifoline, speciofoline, two yohimbine isomers, a yohimbine oxindole and an unidentified indole alkaloid (M⁺, m/e 347) have been obtained from samples of the same species. 3-Iso-ajmalicine, harmane, isopteropodine, pteropodine, uncarine F, speciophylline, isomitraphylline, mitraphylline and N-oxides of these six oxindole alkaloids have been isolated from samples of U. orientalis. Several samples of U. canescens have yielded harmane while one sample contained the four pteropodine isomers. The variation in the alkaloid content of these three species is discussed.     

Structure des caboxines: Alcaloïdes oxindoliques du Cabucala fasciculata

The structures of three new 11-monomethoxy pentacyclic oxindole alkaloids have been elucidated by chemical correlations with reserpinine: caboxine-A was assigned to the allo C₁₉-méthyl α series: 3S, 4R, 7S, 19S; isocaboxine-A and B to the epi-allo C₁₉-methyl α series and have, respectively, the following configurations 3R, 4S, 7S, 19S and 3R, 4S, 7R, 19S.     

Allo-cedrol: A new tricarbocyclic sesquiterpene alcohol

The structure of a new tricarbocyclic sesquiterpene alcohol, named allo-cedrol, was determined by relation with β-acoradiene. The enantiomer of prezizaene and several compounds were obtained from the p-bromobenzenesulfonate of allo-cerol.     

Entadamide B,a second new sulphur-containing amide from Entada phaseoloides

A second new sulphur-containing amide, entadamide B, has been isolated from the dry seeds of Entada phaseoloides Merr. together with entadamide A. Entadamide B was characterized by spectroscopic methods as N-(2-hydroxyethyl)-3,3-bis(methylthi and was synthesized in two steps from propiolic acid.     

Trochelioid A and B,new cembranoid diterpenes from the Red Sea soft coral Sarcophyton trocheliophorum

Chemical investigations of the soft coral Sarcophyton trocheliophorum, has led to the isolation of six cembranoids, two of which are new, Trochelioid A (1) and B (2), and one, 16-oxosarcophytonin E (3) isolated from nature for the first time. Additionally, two have been isolated from S. trocheliophorum for the first time (4 and 6). Structures were elucidated by employing extensive NMR and HR-FAB-MS experimentation.     

Synthesis of the reported structure of homocereulide and its vacuolation assay

Homocereulide, isolated from marine bacterium Bacillus cereus, is an analog of emetic toxin cereulide. There is no report on its structure determination and involvement in B. cereus-associated food poisoning. Homocereulide is a cyclic dodecadepsipeptide composed of l-O-Val-l-Val-d-O-Leu-d-Ala and l-O-allo-Ile-d-Val-d-O-Leu-d-Ala. Here, we synthesized homocereulide using liquid phase fragment condensation. The NMR spectrum of synthesized homocereulide confirmed the intended structure and LC-MS results were consistent with natural products. Morphological evaluation using HEp-2 cells showed higher toxicity with homocereulide (1.39?nM) than cereulide (3.95?nM). Though cereulide is the main component in broth culture, homocereulide is also likely involved in B. cereus-associated food poisoning.     

The role of d-allo-isoleucine in the deposition of the anti-Leishmania peptide bombinin H4 as revealed by 31P solid-state NMR,VCD spectroscopy,and MD simulation

Bombinin H4 is an antimicrobial peptide that was isolated from the toad Bombina variegata. Bombinin H family peptides are active against gram-positive, gram-negative bacteria, and fungi as well as the parasite Leishmania. Among them, bombinin H4 (H4), which contains d-allo-isoleucine (d-allo-Ile) as the second residue in its sequence, is the most active, and its l-isomer is bombinin H2 (H2). H4 has a significantly lower LC50 than H2 against Leishmania. However, the atomic-level mechanism of the membrane interaction and higher activity of H4 has not been clarified. In this work, we investigated the behavior of the conformations and interactions of H2 and H4 with the Leishmania membrane using ³¹P solid-state nuclear magnetic resonance (NMR), vibrational circular dichroism (VCD) spectroscopy, and molecular dynamics (MD) simulations. The generation of isotropic ³¹P NMR signals depending on the peptide concentration indicated the abilities of H2 and H4 to exert antimicrobial activity via membrane disruption. The VCD experiment and density functional theory calculation confirmed the different stability and conformations of the N-termini of H2 and H4. MD simulations revealed that the N-terminus of H4 is more stable than that of H2 in the membrane, in line with the VCD experiment data. VCD and MD analyses demonstrated that the first l-Ile and second d-allo-Ile of H4 tend to take a cis conformation. These residues function as an anchor and facilitate the easy winding of the helical conformation of H4 in the membrane. It may assist to quickly reach to the threshold concentration of H4 on the Leishmania membrane. This article is part of a Special Issue entitled: d-Amino acids: biology in the mirror, edited by Dr. Loredano Pollegioni, Dr. Jean-Pierre Mothet and Dr. Molla Gianluca.     

Purification and characterization of l-allo-threonine aldolase from Aeromonas jandaei DK-39

l-allo-Threonine aldolase (l-allo-threonine acetaldehyde-lyase), which exhibited specificity for l-allo-threonine but not for l-threonine, was purified from a cell-free extract of Aeromonas jandaei DK-39. The purified enzyme catalyzed the aldol cleavage reaction of l-allo-threonine (K_m=1.45 mM, V_max=45.2 μmol min⁻¹ mg⁻¹). The activity of the enzyme was inhibited by carbonyl reagents, which suggests that pyridoxal-5′-phosphate participates in the enzymatic reaction. The enzyme does not act on either l-serine or l-threonine, and thus it can be distinguished from serine hydroxy-methyltransferase (l-serine:tetrahydrofolate 5,10-hydroxy-methyltransferase, EC 2.1.2.1) or l-threonine aldolase (EC 4.1.2.5).     

Prebiotic adenine synthesis from HCN—Evidence for a newly discovered major pathway

Three new imidazole derivatives have been isolated and characterized from oligomerizing HCN solutions. On the basis of these results as well as the earlier identification of a new precursor to adenine, a new and major pathway leading to the formation of adenine is suggested. The route accounts for the synthesis of adenine-8-carboxamide from cis-diamino-maleonitrile, without requiring an isomerization to the trans configuration or reactions with formamidine. The formation of previously reported imidazoles is also explained.     

A pentacyclic quinone diosindigo B from the heartwood of Diospyros melanoxylon

Diosindigo A, diosindigo B and biramentacéone have been isolated from heartwood of Diospyros melanoxylon. A violet pigment isolated from the same source has been shown to be a new pentacyclic quinone. Sunlight causes diosindigo B to change to the pentacyclic quinone and biramentacéone. The intense peaks at m/e 389 and 388 in the mass spectrum of diosindigo B are doublets which arise by fragmentation of both M⁺ and M⁺ + 2.     

An acylated sesquiterpene glycoside from Mortonia gregii

A new glycoside has been isolated from Mortonia gregii and identified by chemical and spectral means as 2-O-β-(2′,6′-diacetyl glucopyranosyl) desacetyl mortonol B.     

Trechonolide A,a new withanolide type from Trechonaetes laciniata

The structure of a new withanolide type isolated from Trechonaetes laciniata, having a hemiacetal ring system and a 5-member ring lactone has been elucidated by X-ray analysis as (23R)-5β,6β-epoxy-12β,17β-dihydroxy-1-oxo-12,22-hemiacetal-ergosta-2,24-dien-23,26-olide (trechonolide A). A second compound (trechonolide B) having at C-12 a β-methoxy group, has also been isolated and assumed to be an artifact since, by heating trechonolide A in methanol with a trace of acid, the methoxy derivative was produced.     

Brickellin,a novel flavone from brickellia veronicaefolia and b. chlorolepis

A new highly oxygenated flavone methyl ether has been isolated from Brickellia veronicaefolia and B. chlorolepis. It has been identified as 5,6′-dihydroxy-6,7,2′,3′,4′-pentamethoxyflavone and given the name brickellin.     

New diterpenes from Porella perrottetiana

Perrottetianal A and perrottetianal B, two new diterpene dialdehydes and a new ent-labdane-type diterpene diol have been isolated from the liverwort Porella perrottetiana and their structures have been elucidated by the chemical and spectral evidence.     

Picrasins,simaroubolides of Japanese quassia tree Picrasma quassioides

From the Japanese quassia tree, Picrasma quassioides (Simaroubaceae), new bitter principles (simaroubolides), picrasin A, B, C, D, E, F and G have been isolated whose stereostructures have been elucidated on the basis of chemical and physical evidence. The relative bitterness of the picrasins and the related simaroubolides has been measured.     

Chondrichthyan teeth from the Early Triassic Paris Biota (Bear Lake County,Idaho, USA)

A new, diverse and complex Early Triassic assemblage was recently discovered west of the town of Paris, Idaho (Bear Lake County), USA. This assemblage has been coined the Paris Biota. Dated earliest Spathian (i.e., early late Olenekian), the Paris Biota provides further evidence that the biotic recovery from the end-Permian mass extinction was well underway ca. 1.3 million years after the event. This assemblage includes mainly invertebrates, but also vertebrate remains such as ichthyoliths (isolated skeletal remains of fishes). Here we describe first fossils of Chondrichthyes (cartilaginous fishes) from the Paris Biota. The material is composed of isolated teeth (mostly grinding teeth) preserved on two slabs and representing two distinct taxa. Due to incomplete preservation and morphological differences to known taxa, the chondrichthyans from the Paris Biota are provisionally kept in open nomenclature, as Hybodontiformes gen. et sp. indet. A and Hybodontiformes gen. et sp. indet. B, respectively. The present study adds a new occurrence to the chondrichthyan fossil record of the marine Early Triassic western USA Basin, from where other isolated teeth (Omanoselache, other Hybodontiformes) as well as fin spines of Nemacanthus (Neoselachii) and Pyknotylacanthus (Ctenachanthoidea) and denticles have been described previously.     

New cyclopeptide alkaloids from Melochia tomentosa

Scutianine B and two new cyclopeptide alkaloids, melonovines A and B have been isolated from Melochia tomentosa.     

Pre-existent Asymmetry in the Human Cyclooxygenase-2 Sequence Homodimer

Prostaglandin endoperoxide H synthase-2 (PGHS-2), also known as cyclooxygenase-2 (COX-2), is a sequence homodimer. However, the enzyme exhibits half-site heme and inhibitor binding and functions as a conformational heterodimer having a catalytic subunit (E_cat) with heme bound and an allosteric subunit (E_allo) lacking heme. Some recombinant heterodimers composed of a COX-deficient mutant subunit and a native subunit (i.e. Mutant/Native PGHS-2) have COX activities similar to native PGHS-2. This suggests that the presence of heme plus substrate leads to the subunits becoming lodged in a semi-stable E_allo-mutant/E_cat-Native∼heme form during catalysis. We examined this concept using human PGHS-2 dimers composed of combinations of Y385F, R120Q, R120A, and S530A mutant or native subunits. With some heterodimers (e.g. Y385F/Native PGHS-2), heme binds with significantly higher affinity to the native subunit. This correlates with near native COX activity for the heterodimer. With other heterodimers (e.g. S530A/Native PGHS-2), heme binds with similar affinities to both subunits, and the COX activity approximates that expected for an enzyme in which each monomer contributes equally to the net COX activity. With or without heme, aspirin acetylates one-half of the subunits of the native PGHS-2 dimer, the E_cat subunits. Subunits having an S530A mutation are refractory to acetylation. Curiously, aspirin acetylates only one-quarter of the monomers of S530A/Native PGHS-2 with or without heme. This implies that there are comparable amounts of two noninterchangeable species of apoenzymes, E_allo-S530A/E_cat-Native and E_allo-Native/E_cat-S530A. These results suggest that native PGHS-2 assumes a reasonably stable, asymmetric E_allo/E_cat form during its folding and processing.     

Clerodane diterpenoids from Teucrium and Ajuga plants

A new clerodane diterpenoid, chamaepitin has been isolated from Ajuga chamaepitys. The previously known clerodanes, 19-acetylgnaphalin, auropolin, teucrin A and teuflin, have been isolated from Teucrium species (T. polium subsp. belion, T. polium subsp. capitatum and T. asiaticum) collected in Majorca. X-ray diffraction analysis on crystals of auropolin has allowed the assignment of configuration at C-20 as S for this compound.     

<Emphasis Type="Italic">“Pseudoalteromonas januaria”</Emphasis> SUT 11 as the Source of Rare Lipodepsipeptides

The marine bacterium “Pseudoalteromonas januaria” SUT 11 isolated from a seawater sample produced the rare cell-bound cyclic lipodepsipeptides A/A′, B/B′, and C/C′. The matrix-assisted laser desorption/ionization mass spectra indicated that one bromine atom presented in the peptides B/B′ and C/C′, whereas the component A/A′ contained no bromine atom. The acyldepsipeptides A/A′–C/C′ have an identical amino acid sequence, Thr-Val-Asn-Asn-Leu/allo-Ile, but differed in C-terminal amino acid and acyl moieties. Peptides A–C have Leu as a C-terminal amino acid, whereas peptides A′-C′ have allo-Ile. Acyl moieties in peptides A/A′, B/B′, and C/C′ have been found to consist of 11-(4′-hydroxyphenyl)-undeca-2,4,6,8,10-pentaenic acid, 9-(3′-bromo-4′-hydroxyphenyl)-nona-2,4,6,8-tetraenic acid, and 11-(3′-bromo-4′-hydroxyphenyl)-undeca-2,4,6,8,10-pentaenic acid, respectively. The structure of a main pair of peptides B/B′ with molecular masses 843/845 Da has been determined by means of ultraviolet, infrared, and two-dimensional nuclear magnetic resonance spectroscopy. We have demonstrated that tandem nano-electrospray ionization mass spectrometry is a very efficient way for the fast and sensitive investigation of lipopeptides A/A′ and C/C′ with molecular masses 791 and 869/871 Da, respectively, which have been isolated in small amounts.