Azaspirene: a novel angiogenesis inhibitor containing a 1-oxa-7-azaspiro[4.4]non-2-ene-4,6-dione skeleton produced by the fungus Neosartorya sp

[structure: see text] Azaspirene isolated from the fungus Neosartorya sp. is a novel angiogenesis inhibitor with a 1-oxa-7-azaspiro[4.4]non-2-ene-4,6-dione skeleton. Azaspirene inhibits the endothelial migration induced by vascular endothelial growth factor (ED100 = 27.1 microM).     

Synthesis of novel antifungal phthalides produced by a wheat rhizosphere fungus

Two antifungal phthalides produced by a wheat rhizosphere fungus have been synthesized using the Alder-Rickert reaction to construct their common isobenzofuranone core structure. The absolute configuration of one of the two phthalides has been determined to be S by synthesizing its (S)- and (R)-enantiomer and comparing their optical rotations with that of the natural product.     

TMC-264, a novel antiallergic heptaketide produced by the fungus Phoma sp. TC 1674

[structure: see text] TMC-264 (1), a novel tricyclic heptaketide with a unique chloro-1H-dibenzo[b,d]pyran-4,6-dione skeleton, was discovered from the fungus Phoma sp. TC 1674. The structure was elucidated on the basis of NMR analyses of normal abundance and biosynthetically (13)C-enriched TMC-264. TMC-264 showed potent inhibitory activity against tyrosine phosphorylation of STAT6.     

Preparation and optical resolution of novel 5,10-diaryloctaethylporphyrins with C2 symmetry

Zinc complex of 5,10-bis(2-hydroxynaphthyl)octaethylporphyrin was prepared by coupling tripyrrole and monopyrrole derivatives in the presence of 2-hydroxynaphthaldehyde. The chiral trans isomer and di(benzyl ether) derivative derived therefrom were successfully resolved into enantiomers by means of HPLC.     

Asymmetric total synthesis of (-)-azaspirene,a novel angiogenesis inhibitor

The asymmetric total synthesis of (-)-azaspirene, an angiogenesis inhibitor, has been accomplished, establishing its absolute stereochemistry. The key steps are a MgBr2.OEt2-mediated, diastereoselective Mukaiyama aldol reaction, a NaH-promoted, intramolecular cyclization of an alkynylamide, and the aldol reaction of a ketone containing functionalized gamma-lactam moiety without protection of tert-alcohol and amide functionalities.     

Nectrianolins A,B, and C,new metabolites produced by endophytic fungus Nectria pseudotrichia 120-1NP

Two sesquiterpene-epoxycyclohexenone conjugates, nectrianolins A (1) and B (2), together with a sesquiterpene, nectrianolin C (3), were isolated from the brown rice culture of Nectria pseudotrichia 120-1NP, an endophytic fungus isolated from Gliricidia sepium. Their structures were determined on the basis of 1D-/2D-NMR spectroscopy and HRESIMS data analyses in combination with chemical means. Nectrianolins A–C (1–3) exhibited cytotoxic activity against both HL60 and HeLa cells.     

Xantholipin, a novel inhibitor of HSP47 gene expression produced by Streptomyces sp.

In the course of our screening program to identify inhibitors of HSP47 gene expression, we obtained a novel aromatic substance from Streptomyces sp. named Xantholipin. Its structure was determined based on physicochemical data of Xantholipin and its derivatives. The absolute configuration was also established by the modified Mosher's method.     

A unique spherical molecular host with D2d symmetry. A novel intramolecular kinetic equilibrium in metal ion complexation between two crown ethers

[formula: see text] A spherical host with D2d symmetry consisting of a tetrathia[3.3.3.3]paracyclophane and two 18-crown-6 moieties was synthesized. Its crystal structure shows a central cavity with a diameter of 1.96 A and a depth of 6.75 A. A Na+ ion could rest in the cavity center but prefers core binding to external binding in one of the crown units. An intramolecular kinetic equilibrium was reached with the Na+ ion switching between the two crown units with an energy barrier of 14.1 +/- 3 kcal/mol.     

Synthesis of marchantin C, a novel microtubule inhibitor from liverworts

Recently, remarkable microtubule inhibitor and anti-tumor activities of the bisbibenzyl marchantin C—isolated from liverworts like Marchantia polymorpha since 1983—were found. In this Letter we describe the first and efficient total synthesis of this subtype of bisbibenzylic compounds with two biarylether connections. The structure was confirmed by the spectroscopic data which were analyzed carefully to exclude any errors in arene connection and substitution pattern.     

Structures of phytotoxins,AV-toxins C,D and E,produced by zonate leaf spot fungus of mulberry

The structures of phytotoxins, AV-toxins C, D and E, produced by zonate leaf spot fungus of mulberry, were characterized.     

A new antibiotic produced by the cyanobacterium-symbiotic fungus Simplicillium lanosoniveum

The culture broth of the cyanobacterium-symbiotic fungus Simplicillium lanosoniveum var. Tianjinienss Q. L. Dong exhibited unanticipated antibacterial activities against the Gram-positive bacteria, particularly the pathogenic bacterium Staphylococcus aureus, indicating the secretion of antibiotic-like metabolite, for which the modified Sabouraud medium was the suitable medium. The antibiotic-like metabolite was separated with macroporous resins CT-12 (absorption) and 95% ethanol (desorption), purified by ion-exchange resins D301T and displayed a characteristic absorption peak at 228 nm, suggesting the presence of nitrogen. The negative biuret and ninhydrin tests confirmed the absence of –NH₂ and –COOH groups. Further, HPLC and mass spectrometry analyses showed that the retention time and molecular weight of the antibiotic-like metabolite were 4.1031 min and 163.0182 (Δ ± 2.3 ppm), respectively. Taking together, we speculated that the antibiotic-like metabolite was a new antibiotic structurally similar to alkaloid, which was the first one isolated from the species of Simplicillium genus.     

Chemiluminescence from C2 produced by C3 oxidation

The reaction of molecular carbon vapor with oxygen has been studied in a flowing system. For an equilibrium disitribution of carbon molecular species at 2470 K, the dominant reaction observed was: C₃ + O₂ → C^*₂(d³II, ν′ = 1) + CO + O (or CO₂). Of the product species, only excited C₂ was detected. From these measurements a lower bound on the rate constant has been determined to be k ≥ 2 × 10^?12 cm³/s.     

Pyrene-linked triazole-modified homooxacalix[3]arene: a unique C3 symmetry ratiometric fluorescent chemosensor for Pb2+

A new type of fluorescent chemosensor based on homooxacalix[3]arene was synthesized. The fluorescent sensor was highly selective for Pb(2+) in comparison with other metal ions tested by enhancement of the monomer emission of pyrene. The C(3) symmetric structure of homooxacalix[3]arene has potential application in the development of a new ratiometric fluorescent chemosensor for heavy metal ions.     

Citrinadin A, a novel pentacyclic alkaloid from marine-derived fungus Penicillium citrinum

[structure: see text] A novel pentacyclic alkaloid, citrinadin A (1), was isolated from the cultured broth of the fungus Penicillium citrinum, which was separated from a marine red alga, and the structure was elucidated by spectroscopic data. The relative stereochemistry of the pentacyclic core was assigned on the basis of NOESY data and (1)H-(1)H coupling constants, and the presence of an N,N-dimethyl-L-valine residue in 1 was determined by chiral HPLC analysis of the hydrolysate.     

Perinadine A, a novel tetracyclic alkaloid from marine-derived fungus Penicillium citrinum

[structure: see text] A novel tetracyclic alkaloid, perinadine A (1), was isolated from the cultured broth of the fungus Penicillium citrinum, which was separated from the gastrointestine of a marine fish, and the structure was elucidated on the basis of spectroscopic data including 2D NMR spectra. Biogenetically, perinadine A (1) may be derived from citrinin (4), a well-known mycotoxin, and a scalusamide A-type pyrrolidine alkaloid.     

Cytochalasins D1 and C1, unique cytochalasans from endophytic fungus Xylaria cf. curta

Cytochalasins D1 (1) and C1 (2) were isolated from the liquid fermentation of fungus Xylaria cf. curta. Their structures and absolute configurations were determined by comprehensive experimental spectroscopic methods as well as ECD and GIAO ¹³C NMR calculation. They possess a unique eleven-membered macrocycle with an oxygen bridge. Cytochalasins D1 and C1 showed moderate cytotoxicity against human leukemia cell lines HL-60 with IC₅₀ value of 12.7 and 22.3 μM, respectively.     

Argadin, a new chitinase inhibitor, produced by Clonostachys sp. FO-7314

A new chitinase inhibitor, designated as argadin (1), was isolated from the cultured broth of a fungal strain FO-7314. The strain was identified as Clonostachys sp. from the morphological characteristics. Argadin was purified from the cultured mycelium by a combination of cation exchange, adsorption and gel filtration chromatographic methods. The structure of argadin was elucidated as cyclo(Nomega-acetyl-L-arginyl-D-prolyl-homoseryl-histidyl-L- 2-aminoadipyl) in which homoseryl gamma-methylene bonded to histidyl alpha-amino residue. The IC50 value of argadin against Lucilia cuprina (blowfly) chitinase was 150 nM at 37 degrees C and 3.4 nM at 20 degrees C. Argadin arrested the moult of cockroach larvae upon injection into the ventral abdominal part.     

RK-805, an endothelial-cell-growth inhibitor produced by Neosartorya sp., and a docking model with methionine aminopeptidase-2

We found that a fungus Neosartorya sp. produced an angiogenesis inhibitor, RK-805. By spectroscopic analyses and semi-synthetic methods from fumagillin, the structure of RK-805 was identified as 6-oxo-6-deoxyfumagillol, which has not been reported as a natural product. RK-805 preferentially inhibited the growth of human umbilical vein endothelial cells (HUVECs) rather than that of human normal fibroblast in cell proliferation assays and blocked endothelial cell migration induced by vascular endothelial growth factor (VEGF). Moreover, RK-805 selectively inhibited methionine aminopeptidase-2 (MetAP2), but not methionine aminopeptidase-1 (MetAP1). The docked structure of RK-805 complexed with human MetAP2 indicated that not only a covalent bond between a nucleophilic imidazole nitrogen atom of His231 and the carbon of the reactive spirocyclic epoxide of RK-805, but also a hydrogen bond between NH (Asn329) and the carbonyl group of RK-805 at C-6 promote close contact in the binding pocket of the enzyme. Taken together, these results suggest that structure activity relationships of RK-805 derivatives at both C-4 and C-6, in comparison with ovalicin and TNP-470, would be useful for development of new angiogenesis inhibitors.     

A unique example of a high symmetry three- and four-connected hydrogen bonded 3D-network

We present a three- and four-connected 3D-net based on 4-aminopyridine coordinated to Ag(I) and hydrogen bonded to nitrate with the unusual, high symmetry, topology (8(3))(8(6))2-tfa.