Golmaenone, a New Diketopiperazine Alkaloid from the Marine-Derived Fungus Aspergillus sp.

Abstract

A new diketopiperazine alkaloid, golmaenone (1) and related alkaloids, neoechinulin A (2) and L-alanyl-L-tryptophan anhydride (3), have been isolated from the culture broth of the marine-derived fungus Aspergillus sp. The structure and absolute stereochemistry of the new compound (1) was assigned by spectroscopic methods and the advanced Marfey's method. Compounds 1 and 2 exhibited a significant radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) with IC 50 values of 20 and 24 m mM, respectively, which are similar to the positive control, ascorbic acid (IC 50 , 20 m mM). Compounds 1 and 2 also showed an ultraviolet-A (UV-A) (320-390 nm) protecting activity with ED 50 values of 90 and 170 m mM, respectively, which are more active than oxybenzone (ED 50 , 350 m mM) currently being used as sunscreen.Key words diketopiperazine alkaloid; golmaenone; neoechinulin A; L-alanyl-L-tryptophan anhydride; marine-derived fungus; Aspergillus sp.Diketopiperazines are widespread microbial products commonly found in nutrient rich cultures of both terrestrial 1) and marine fungi.2,3) Diketopiperazines are of interest because of their activity in various pharmacological assay systems. 4)As part of a program to explore the bioactive metabolites produced by the fungi isolated from marine habitats, 5) we investigated the bioactive constituents of the marine algicolous fungus and isolated a new golmaenone (1) in addition to neoechinulin A (2) and L-alanyl-L-tryptophan anhydride (3).A fungal strain (culture # MFA 212) was isolated from the surface of the marine red alga Lomentaria catenata collected at Golmae Village, Ulsan City, Korea in 2002, and it was identified by fatty acid methyl ester anlaysis (FAME) as a Aspergillus sp.6) The fungus was cultured (10 l) in a seawaterbased medium. 7)The culture broth and mycelium were separated, and the broth was extracted with ethyl acetate to provide a crude extract (1.5 g), which was subjected to a combination of column chromatography on silica gel (n-hexane/EtOAc) and octadesyl silica (ODS) gel (H 2 O/MeOH) to furnish three fractions containing diketopiperazines 1 (20 mg), 2 (120 mg), and 3 (35 mg). Further purifications of each fraction by HPLC (YMC ODS-A, MeOH) yielded a new golmaenone (1) (12 mg), as well as neoechinulin A (2) (95 mg) and Lalanyl-L-tryptophan anhydride (3) (7 mg).Golmaenone (1) Table 1).The connection of the functional groups in 1, which led to the planar structure, was achieved on the basis of HMQC and HMBC correlations. Key HMBC correlations between H-15 and C-2, C-6 and C-16; between H-3 and C-7; between H-8 and C-7 and C-10; between H 3 -20/21 and C-16 and C-18; and between H-14 and C-8, C-10 and C-12, clearly estab- Fig. 1 lished the planar structure of 1.The geometry of C-8/C-9 double bond in compound 1 was determined to be (Z) configuration on the basis of the chemical shifts of H-8 [d 7.22 (1H, s)] and H-14 [d 11.57 (1H, s)], which were shifted to the low field by the deshielding effect of the carbonyl group on b-vinyl proton 9) and by the hydr...

Cristazine, a New Cytotoxic Dioxopiperazine Alkaloid from the Mudflat-Sediment-Derived Fungus <i>Chaetomium cristatum</i>

“…[5][6][7][8] Radical Scavenging Assays 15) Biological activity was measured exactly as described in our previous paper.…”

“…This paper describes the isolation and structural characterization of a new dioxopiperazine alkaloid, cristazine (1), and the known chetomin (2), 5,6) neoechinulin A (3), 7,8) and golmaenone (4) 7) from C. cristatum.…”

“…2,3) As part of a program to explore the bioactive metabolites produced by fungi isolated from marine habitats, we directed our efforts towards the microorganisms associated with the sediments of marine mudflats, 4) and isolated the fungal strain Chaetomium cristatum. This paper describes the isolation and structural characterization of a new dioxopiperazine alkaloid, cristazine (1), and the known chetomin (2), 5,6) neoechinulin A (3), 7,8) and golmaenone (4) 7) from C. cristatum.…”

Synthetic and Structure-Activity Relationship Studies on Bioactive Natural Products

“…30,32) II. Neoechinulin A Neoechinulin A (25), an indole alkaloid, has been isolated from Aspergillus sp., [33][34][35][36][37][38][39][40][41][42] ascomysete Xylaria eulossa, 43) endophytic fungus Chaetomium globosum,…”

Diketopiperazines from the Cordyceps-Colonizing Fungus Epicoccum nigrum

“…[1][2][3] Naturally occurring DKPs have frequently been isolated from fungal sources. Examples include golmaenone, a radical scavenger from a marine-derived Aspergillus sp., 4 the rostratins, cytotoxic DKP disulfides from a marine-derived Exserohilum rostratum, 5 the epicorazines, antibacterial metabolites from a basidiomycete Stereum hirsutum, 6 and the verticillins, dimeric DKPs from a marine-derived Penicillium sp. 7 Cordyceps sinensis (Berk.)…”