Based on the above data, the structure of 1 was determined and it was named as penicibrocazine A.Ĭompound 2 was obtained as yellowish solid. The negative CE around 254 nm is indicative for the 2 R configuration of TDKPs. The Electronic Circular Dichroism (ECD) spectrum of 1 showed negative Cotton Effect (CE) at 254 nm and positive CE at 218 nm ( Supplementary Information). The Cu/Kα radiation allowed the assignment of the absolute configuration of all the stereogenic centers in 1 as 2 R, 4 R, 8 S, 9 S, 2' S, 4' S, 8' S, and 9' S. An X-ray crystallographic experiment ( Figure 4) confirmed the structure and relative configuration of 1. The NOE correlations from SCH 3-2 to H-8, H-2', and H-8' as well as from H-8' to H-2' and H-4' indicated the same orientation of these groups ( Figure 3). The coupling constants for H-4 and H-9 ( J H-4/H-9 = 8.0 Hz) as well as for H-4' and H-9' ( J H-4 ' /H-9 ' = 12.8 Hz), revealed the cis-relationship between H-4 and H-9 and trans-relationship of H-4' and H-9'. The relative configuration of compound 1 was determined by analysis of its 1H- 1H coupling constants and NOESY experiment. Α 2.59, ddd (18.2, 12.4, 5.2) β 2.27, m (overlap)Ī Measured in CDCl 3 b Measured in DMSO- d 6 c Measured in acetone- d 6. This deduction was confirmed by the 1H- 1H COSY correlations from H 2-3' to H-2' and H-4' as well as by the observed HMBC correlations from H-2' and H-3' to C-1' and from H-4' to C-2', as shown in Figure 2. Moreover, signals for one of the two S-methyl groups (δ H 1.90/δ C 14.2, CH 3) in epicoccin G was absent in the NMR spectra of 1, indicating the lack of a S-methyl group in 1. Instead, resonances for a methine group at δ H 4.57 (H-2') and δ C 59.6 (C-2') were observed in the NMR spectra of 1 ( Table 1 and Table 2). However, the signal for a quaternary carbon resonating at δ C 71.6 (C-2') in epicoccin G was absent in the 13C NMR spectrum of 1. The NMR data of 1 revealed some structural similarities to epicoccin G, a disulfide diketopiperazine isolated from the fungus Epicoccum nigrum. Detailed analyses of the 1H and 13C NMR data ( Table 1 and Table 2, Supplementary Figures S1 and S2) indicated the presence of one methyl, six methylenes, seven sp 3 methines, and five quaternary carbons (including two ketones and two ester/amide carbonyl carbons). Its molecular formula was determined as C 19H 2 4N 2O 6S on the basis of HRESIMS, implying nine degrees of unsaturation. Structure Elucidation of the New CompoundsĬompound 1 was obtained as colorless crystals. Details of the isolation, structure elucidation, and biological activity of compounds 1– 6 are reported herein.Ģ.1. All these compounds were examined for cytotoxic and antimicrobial activities. The structures of these compounds were determined by detailed analysis of the NMR and mass spectrometric data and compounds 1 and 3 were confirmed by single-crystal X-ray diffraction analysis. Further work on the remaining fractions of the fungus resulted in the isolation of five new sulfide diketopiperazine derivatives, namely, penicibrocazines A–E ( 1– 5) and one known analog ( 6) ( Figure 1). Very recently, six new cytotoxic bisthiodiketopiperazine derivatives, brocazines A–F, have been isolated from the culture extract of Penicillium brocae MA-231, an endophytic fungus obtained from the fresh tissue of the marine mangrove plant Avicennia marina. As part of our recently initiated program aimed at the discovery of bioactive secondary metabolites from marine-derived fungi, a series of structurally interesting and biologically active natural products has been described. Thiodiketopiperazine derivatives, which generally possess a 6-5-6-5-6 diketopiperazine skeleton with a disulfide bridge or S-methyl group(s), have attracted considerable attention due to their diversified structures and potent biological activities.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |