Cinatrins, a novel family of phospholipase A2 inhibitors. I. Taxonomy and fermentation of the producing culture; isolation and structures of cinatrins.

Abstract

Cinatrins A, B, Cl5 C2 and C3, a family of phospholipase A2 inhibitors were isolated from the fermentation broth of Circinotrichum falcatisporum RF-641. They were found to be novel spiro-y-dilactones and y-lactones derived from 1 ,2,3,5-tetra or 1 ,2,3(or l ,2,4)-trihydroxypentadecane-1,2,3-tricarboxylic acids. Structures were elucidated by MSand NMRstudies and chemical transformations. The structure of cinatrin C3 was confirmed by X-ray crystallographic analysis, and its absolute configuration was determined by comparison of the CDspectra with related compounds.In a screening program for unique microbial products with pharmacological activity, the phospholipase A2 (PLA2) inhibitors cinatrins A (la), B (2a), Cx (3a), C2 (4a) and C3 (5a) were isolated from the fermentation broth of Circinotrichumfalcatisporum strain RF-641. The taxonomy, fermentation, isolation, physico-chemical properties and structures of cinatrin congeners are described in this paper. The biological properties are reported in a companionpaper.1} Taxonomy Strain RF-641 does not show typical morphological properties on agar media, and the properties shown on a leaf of Indian-rubber-tree (Ficus elastica) are described. Colonies are punctiform to effused, dark brown to black, hairy, and composed of dark, branched and anastomosing hyphae bearing setae and sporogenous cells. Setae arising from dark brown, thick-walled and swollen cells of the superficial mycelium, are numerous, simple, erect, thick-walled, sparsely, and indistinctly septate, roughened, dark brown, opaque, darker near the base, paler towards the apex which is circinate or spirally twisted. Sporogenouscells are numerous, arising laterally on the superficial hyphae, obclavate to lageniform, thin-walled, subhyaline. Conidia are adherent, persisting at the bases of the setae in the form of a whitish pellicle, falcate with acute ends, 18.5~20.0 x X.l^va. Based on the taxonomic properties described above, strain RF-641 was identified as Circinotrichum falcatisporum Pirozynsky (1962).2) Strain RF-641 has been deposited at the Fermentation Research Institute, Agency of Industrial Science and Technology, Japan, under the accession No. FERM P-10681. FermentationA slant culture of strain RF-641 was inoculated into a seed medium (100ml) containing Polypepton 1.0%, glucose 2.0%, beef extract 0.3%, yeast extract 0.2%, NaCl 0.1%, and tap water (pH 7.0) in a 500-ml Sakaguchi flask, and cultured at 28°C for 72 hours on a rotary shaker at 120 rpm. The seed culture was used at the rate of4% to inoculate 100ml of the production mediumin each of one hundred 500-ml Erlenmeyer flasks and cultivation was carried out at 28°C for 96 hours under agitation at 180rpm. The

Ascotricins A and B, novel antagonists of sphingosine-1-phosphate receptor 1 from Ascotricha chartarum Berk. SANK 14186

“…Therefore, ascotricins A and B are novel antagonists of S1P 1 . We also found that aranorosin, 22 analogs of caloporoside 23 and cinatrins 24,25 had S1P 1 antagonist activity (data not shown). All of these, including ascotricins, are amphipathic compounds and are also thought to be analogs of Sph-1-P. Ascotricins inhibited HUVEC migration, and this indicates that ascotricins and their related S1P 1 antagonists might have antiangiogenic activity.…”

Abundance and Diversity of Mould Inhabiting Muara Layang Estuary Sediment, Bangka Belitung Islands

“…Coelomycetes is typically found in leaf litter. However, most of Coelomycetes was not sporulated while culturing in the laboratory (Itazaki et al, 1992). Number of those moulds can only be identified based on morphology reproduction structure in their host.…”

A Facile and Efficient Synthesis of Functionalized γ-Butyrolactones from Baylis - Hillman Adducts of Isatin

“…Found: 297.1366. (m,2H,Ar). δ C (CDCl 3 , 75 MHz) 11.35, 25.93, 41.18, 64.45, 79.68, 109.22, 112.80, 127.56, 131.85, 132.72, 140.32, 180.81 11.21,41.16,64.30,79.98,109.31,113.40,127.35,132.50,132.81,140.00,190.79.…”

“…R F 0.5 (50:50 hexane/EtOAc). ν max /cm −1 (CH 2 Cl 2 ) 3405 (OH, NH), 2941, 1781, 1718, 1600. δ H (CDCl 3 , 300.1 MHz) 0.61 (d, J 6.9, 3H, CH 3 ), 1.94 (br s, 2H, OH and NH), 2.5 (m, 1H), 3.92 (dd, J 11.1 and 4.5, 1H), 4.18 (dd, J 11.1 and 9.6, 1H), 4.75 (d, J 15.6, 1H), 4.98 (d, J 15.6, 1H), 6.57 (d, J 8.1, 1H, Ar), 7.28-7.48(m, 7H, Ar). δ C (CDCl 3 , 75 MHz)11.59, 41.11, 64.65, 79.64, 104.78, 116.21, 122.11, 123.44, 127.01, 127.21 (2C), 127.89 (3C), 130.01, 132.39, 141.82, 196.58.…”