Peniciadametizine A, a Dithiodiketopiperazine with a Unique Spiro[furan-2,7'-pyrazino[1,2-b][1,2]oxazine] Skeleton, and a Related Analogue, Peniciadametizine B, from the Marine Sponge-Derived Fungus Penicillium adametzioides

Abstract

Peniciadametizine A (1); a new dithiodiketopiperazine derivative possessing a unique spiro[furan-2,7'-pyrazino[1,2-b][1,2]oxazine] skeleton, together with a highly oxygenated new analogue, peniciadametizine B (2); as well as two known compounds, brasiliamide A (3); and viridicatumtoxin (4), were isolated and identified from Penicillium adametzioides AS-53, a fungus obtained from an unidentified marine sponge. The unambiguous assignment of the relative and absolute configuration for the spiro center C-2 of compound 1 was solved by the combination of NMR and ECD measurements with Density-Functional Theory (DFT) conformational analysis and Time-Dependent Density-Functional Theory-Electronic Circular Dichroism (TDDFT-ECD) calculations. The spiro[furan-2,7'-pyrazino[1,2-b][1,2]oxazine] skeleton of 1 has not been reported yet among natural products and the biosynthetic pathway for 1 and 2 was discussed. Compounds 1 and 2 showed inhibitory activity against the pathogenic fungus Alternaria brassicae.

Marine natural products

“…232 Of these, nectriapyrone D 232 342 was simultaneously isolated from a terrestrial fungus as gulpyrone B. 233 244 Penicitrinine A, 375 also with a unique spiro skeleton, was obtained from P. citrinum and was cytotoxic to a wide range of tumour cell lines. It also induced apoptosis and suppressed metastasis.…”

Bioactive Compounds Produced by Strains of Penicillium and Talaromyces of Marine Origin

“…Widely considered as a model organism used to test the toxicity of chemicals, brine shrimp ( Artemia salina ) has been employed for demonstrating the toxic effects of products such as 6,7-dihydroxy-3-methoxy-3-methylphthalide [ 132 ], 13- O -prenyl-26-hydroxyverruculogen [ 148 ], adametizine A [ 155 ], the peniciadametizines [ 156 ], and the communesins [ 51 ]. The latter represent a numerically expanding series of cytochalasan alkaloids which have been also introduced to some extent for cytotoxic/antiproliferative properties ( Table 2 ), and insecticidal effects resulting after oral administration to silkworms [ 215 ].…”

Current Status and Future Prospects of Marine Natural Products (MNPs) as Antimicrobials

“…Peniciadametizine A ( 30 ), a dithiodiketopiperazine derivative possessing a unique spiro [furan-2,7′-pyrazino[1,2-b][1,2]oxazine] skeleton, and its highly oxygenated analogue, peniciadametizine B ( 31 ) were isolated from Penicillium adametzioides AS-53, a fungus obtained from an unidentified marine sponge collected in Wenchang, Hainan, China. These compounds exhibited selective activities against A. brassicae but were inactive against bacteria ( Aeromonas hydrophilia , Edwardsiella tarda , E. coli , S. aureus , Vibrio alginolyticus , V. anguillarum , V. parahaemolyticus , and V. harveyi ), and plant-pathogenic fungi ( Colletotrichum gloeosporioides , Fusarium graminearum , and Gaeumannomyces graminis ) [ 38 ]. The antimicrobial sulfide diketopiperazine derivatives, penicibrocazines A–E ( 32 – 36 ), were isolated from a culture extract of Penicillium brocae MA-231, an endophytic fungus obtained from the fresh tissue of the marine mangrove plant Avicennia marina .…”