Secondary metabolites by chemical screening. 8. Decarestrictines, a new family of inhibitors of cholesterol biosynthesis from Penicillium. I. Strain description, fermentation, isolation and properties.

Abstract

A family of new 10-membered lactones was detected by chemical screening. Taxonomic studies and fermentation conditions of the producing organisms, which belong to the species Penicillium simplicissimumand Penicillium corylophilum, are presented. Theisolation as well as physico-chemical data of the new compoundsnameddecarestrictines A to D are reported. In vitro testing using the HEP-G2cell assay showed the decarestrictines to be inhibitors of cholesterol biosynthesis, which could be confirmed in vivo. In addition to the decarestrictines from P. corylophilum epoxyagroclavine-I(1) was isolated.Within our concept2~5) to detect new secondary metabolites by chemical screening6'7*, we isolate and characterize microorganisms from various natural sources, e.g. soil samples, plant material, and foodstuff. The culture broths and the mycelia of the newly isolated and immediately cultivated strains were extracted by organic solvents. The obtained residues were dissolved in small amounts of methanol -water (1 : 1) and analyzed by TLCchromatography in different solvent systems by treatment with various staining reagents.This procedure renders a good visualization of the characteristic secondary metabolite pattern of each strain. Applying this method to various microorganisms it has been found that different Penicillium species (strains FH-A 6090, FH-A 6099, FH-A 6530, and FH-A 6360) exhibit a similar but unusual secondary metabolite pattern. The present paper deals with the description of the producing organisms, their fermentation conditions, isolation and purification procedures as well as the physico-chemical and biological properties of the newsecondary metabolites, named decarestrictines A to D. In an accompanying paper8), the structural elucidation of these novel 10-memberedlactones will be presented in detail. In addition, from strain FH-A 6360 the ergot alkaloid epoxyagroclavine-I (l)9'10) was isolated. Description of the Producing OrganismsThe decarestrictine-producing strains FH-A 6090, FH-A 6099, FH-A 6530, and FH-A 6360 were f Seerefl.

Hydrolytic Kinetic Resolution as an Emerging Tool in the Synthesis of Bioactive Molecules

“…60 to its further elaboration to the anti-1,3-amino alcohol moiety. Thus, epoxide 156 was treated with (S,S)-(salen)Co(III)OAc complex 1b (0.5 mol%) and water (0.55 equiv) in tetrahydrofuran (0.55 equiv) to afford the epoxide 157 as a single stereoisomer (determined from 1 H and 13 C NMR spectroscopic analysis) in 46% yield and the diol 158 in 47% yield.…”

Nonanolides of Natural Origin: Structure, Synthesis, and Biological Activity

“…NMR spectroscopy in combination with X-ray crystal structure analyses, Mosher's method, [ ] D values, CD, or quantum chemical CD calculations were extensively used in the elucidation of the relative and absolute configurations of nonanolides. In some cases, the absolute stereochemistry of nonanolides, for example putaminoxin (35) [44], mueggelone (39) [45], sporostatin (53) [46], multiplolide A (4) [47], xestodecalactones A, B and C (54)(55)(56) [48][49][50], and achaetolide (49) [41,51] were established by stereoselective total synthesis. The nonanolide class of metabolites is classified according to the previously established criteria: (i) simple nonanolides with methyl and oxygen substituents (Fig.…”

“…The structures and relative configurations were determined by analysis of NMR data and X-ray crystallographic analysis. Lactone 10 was structurally related to decarestrictine C 1 , which was isolated from Penicillium simplicissimum and P. corylophilum [53,54], differing only in the configuration at C-6. Compounds 11 and 12 were C-4 epimers [29].…”

“…Cyanobacterium [8,9] Aspinolides A-C (1-3) Aspergillus chraceus (DSM-7428) Fungus [19] Sporostatin (M5032) (53) Sporormiella sp. M5032 Fungus [20] Herbarumins I-III (40)(41)(42) Phoma herbarum Fungus [21,22] Pyridomacrolidin (52) Beauveria bassiana Fungus [23,24] Microcarpalide (43) Unidentified Endophytic fungus [25] Multiplolides A, B (4, 5) Xylaria multiplex BCC 1111 Fungus [26] Xestodecalactones A-C (54-56) Penicillium cf.…”

Antibiotics inhibiting the biosynthesis of cholesterol (a review)

“…was comparable to that ofclofibrate at 100mg/kg. Besides the hypolipidemic action, decarestrictin D exhibits antiviral activity [95,96].…”