New zearalenone related macrolides and isocoumarins from an unidentified fungus

Abstract

acetate [ll/3,21 .dihydroxypregna-1,4-dien-3,20-dione 21-acetate] in 10 mL of dry tetrahydrofuran was added via the addition funnel, and the funnel was washed with an additional 10 mL of solvent. TLC indicated the reaction was complete after 2 h and the solution was poured into water and adjusted to a pH of ca. 4 with acetic acid. From this aqueous suspension, 821 mg (2.01 mmol, 78%) of 13 slowly crystallized: mp 187-194 "C (ethyl acetate-cyclohexane); IR 3400,2220, 1750,1665,1615,1605 cm-I; UV 218 nm (c 25 000); NMR 8 7.35 (d, J = 10 Hz, 1 H), 6.28 (dd, The Formation of the Cardenolide 14 from the 1,4-Dien-3-one 13. To a solution of 13 (350 mg, 0.86 mmol) in 50 mL of ethanol was added 2.5 mL of distilled water and 0.5 g of p-toluenesulfonic acid monohydrate. The reaction mixture was refluxed for 16 h, cooled, and diluted with 150 mL of distilled water. The precipitate was filtered, dried, and crystallized from methylene chloridine-ethyl acetatepetroleum ether to yield 205 mg (0.57 mmol, 65%) of cardenolide 14 as the monohydrate: mp 256269 "C; IR 3450,1780,1750,1660,1625, 1660 cm-l; UV 220 nm ( t 21 OOO), 244 (sh, 15 500); NMR (MezS0-d~) 6 7.37 (d, J = 10 Hz, 1 H), 6.17 (dd, J = 10,2 Hz, 1 H), 5.95 (m, 2 H), 4.The isolation and characterization of four new zearalenone-like macrolides and three isocoumarins from an unidentified fungus, Lederle Culture 21640, are reported. By altering the fermentation conditions this organism could be forced to produce curvularin macrolides. X-ray studies on a di-p-chlorobenzoyl derivative of LL-Z1640-1 showed this metabolite to be (4'S,5'S)-4',5'-dihydroxyzearalenone 4-methyl ether.

3,4,5,6,9,10-Hexahydro-14,16-dihydroxy-3-methyl-1H-2-benzoxacyclotetradecin-1,7(8H)-dione (Zearalenone)

“…Bond distances and angles are in agreement with those of related structures reported by Taylor & Watson (1976) and Ellestad et al (1978). This molecule consists of one phenyl (C16-C21) ring fused to a 14-membered lactone ring (C1-C10, Oll, C12, C16, C21)0.…”

E6201 [(3S,4R,5Z,8S,9S,11E)-14-(Ethylamino)-8, 9,16-trihydroxy-3,4-dimethyl-3,4,9,19-tetrahydro-1H-2-benzoxacyclotetradecine-1,7(8H)-dione], a Novel Kinase Inhibitor of Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase (MEK)-1 and MEK Kinase-1: In Vitro Characterization of Its Anti-Inflammatory and Antihyperproliferative Activities

“…f152A1 was reported previously as LL-Z1640-2 (Ellestad et al, 1978) or 5Z-7-oxo-zeaenol (Rawlins et al, 1999). The biological activities of f152A1 and its derivatives have been reported: inhibition of growth and motility of ciliated protozoan T. pyriformis (Ellestad et al, 1978); inhibition of IL-1␤ release from human monocytes (Kastelic et al, at ASPET Journals on May 11, 2018 jpet.aspetjournals.org Downloaded from 1996); inhibition of endotoxin-induced TNF␣ production from U937 cells (Rawlins et al, 1999); inhibition of T-cell activation (Camacho et al, 1999), Ras signaling (Tanaka et al, 1999), JNK/p38 pathways (Takehana et al, 1999), and TAK1 activation (Ninomiya-Tsuji et al, 2003); and inhibition of MEK (Zhao et al, 1999;Ohori et al, 2007). The number of reported in vivo effects of f152A1 and related compounds is more limited.…”

“…This compound was originally reported as LL-Z1640-2, a zearalenone-like compound with modest inhibitory activity on growth and motility of the ciliated protozoan Tetrahymena pyriformis (Ellestad et al, 1978) and is now known as 5Z-7-oxo-zeaenol (Rawlins et al, 1999). Because f152A1 is readily metabolized in biological fluids (plasma and liver microsomes) into pharmacologically inactive metabolites, the synthesis of analogs of f152A1 was undertaken to obtain metabolically stable compounds.…”

Resorcylic acid lactones as new lead structures for kinase inhibition

“…As the first cis-enone-containing resorcylic acid lactone, compound LL-Z1640-2 (1) was isolated in 1978 from an unidentified fungus (''Lederle culture Z1640''), but at the time was not found to be associated with any interesting biological activity [16]. Hypothemycin (2) was first isolated by Nair and Carey as a moderately active antibiotic from a strain of Hypomeces trichothecoides in 1980 [17]; however, the correct structure of the compound was only established after re-isolation from Coriolus versicolor by Agatsuma et al in 1993 [18].…”