Structure of verruculogen, a tremor producing peroxide from Penicillium verruculosum

New prenylated indole alkaloids from fungus Penicillium sp. derived of mangrove soil sample

“…The combined extract was fractionated by a combination of column chromatography (CC) on Si gel, reversed-phase Si gel C18, and Sephadex LH-20 as well as by semi-preparative HPLC and preparative thin layer chromatography (pTLC), to yield seven indolediketopiperazine derivatives (1-7) (Figure 1 and two ester/amide carbons), as well as three exchangeable protons ( Table 1). The 1 H-and 13 C-NMR data assignments matched well with those of the corresponding signals for verruculogen (4), a tremorgenic mycotoxin peroxide isolated from peanuts-derived fungus Penicillium verruculosum [4,5], except for the presence of the C-24 hydroxy group, which was consistent with the difference in the molecular formula. This difference was supported by the fact that the NMR signals for one of the two methyls in the prenyl moiety of 4 [4,5] were replaced by the downfield oxygenated CH 2 signals at δ H 3.80/δ C 65.2 (CH 2 -24) in the NMR spectra of 1 ( Table 1).…”

“…The 1 H-and 13 C-NMR data assignments matched well with those of the corresponding signals for verruculogen (4), a tremorgenic mycotoxin peroxide isolated from peanuts-derived fungus Penicillium verruculosum [4,5], except for the presence of the C-24 hydroxy group, which was consistent with the difference in the molecular formula. This difference was supported by the fact that the NMR signals for one of the two methyls in the prenyl moiety of 4 [4,5] were replaced by the downfield oxygenated CH 2 signals at δ H 3.80/δ C 65.2 (CH 2 -24) in the NMR spectra of 1 ( Table 1). The HMBC correlations from H-22 to C-24 and C-25, from H 2 -24 to C-22 and C-23, and from H 3 -25 to C-22, C-23, and C-24 verified the above deduction ( Figure 2).…”

“…Some of these compounds showed tremor-producing, cytotoxic, antibacterial, and brine shrimp lethal activity [3][4][5][6][7]. In our continuing investigation aimed to explore new and bioactive secondary metabolites from marine-derived fungi [9][10][11][12][13][14][15], we recently focused on a fungal strain Penicillium brefeldianum SD-273 that was isolated from the sediment samples collected from the estuary of the Pearl River in the South China Sea.…”

“…Indolediketopiperazine alkaloids are a series of natural occurring secondary metabolites generally formed from L-tryptophan and other common amino acids, e.g., L-proline, L-alanine, and D-valine [1][2][3][4][5][6][7][8].…”

Pharmacological Effects of the Tremorgenic Mycotoxin Fumitremorgin A

“…The chemical structure of FTA was es tablished by Yamazaki et al in 1975 (2). It contains an indole and a diketopyperazine moiety, and the whole structure has much in common with verruculogen, a similar mycotoxin described by Cole et al (3,4). Several indolic mycotoxins have been reported to have violent motor effects in mammals (5)(6)(7)(8), and it has been pointed out that these mycotoxins might be responsible for naturally occurring neurological disorders in domestic animals (9).…”