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Antipodal (−)-versicolamide B and notoamides L-N were isolated from a marine-derived Aspergillus sp. The possible biosynthetic pathway of enantiomeric pairs of notoamide B and versicolamide B are proposed. Notoamide L is the first metabolite containing twenty-five carbons in the related prenylated indole alkaloids. Notoamide M is potentially a precursor to the proposed azadiene species involved in the putative intramolecular Diels-Alder reaction in the biogenesis of the bicyclo[2.2.2]diazaoctane ring system. A number of prenylated indole alkaloids containing a diketopiperazine or a bicyclo[2.2.2] diazaoctane ring were isolated from various fungi of the genera Aspergillus and Penicillium, and the study of the biosynthetic pathways to these alkaloids has recently become an area of significant interest. 1 We isolated new alkaloids, notoamides A-D (1-4), 2 ( Figure 1) from a marine-derived Aspergillus sp. as well as the known natural product stephacidin A (5). 3 Interestingly, we found that notoamide E (6) is a short-lived natural metabolite and biosynthetic precursor to notoamides C (3) and D (4). 4 In addition, we recently isolated notoamides F-K. 5 Further, Williams and Gloer et al. reported the isolation of antipodal (+)-notoamide B (7) and (−)-stephacidin A (8) (Figure 2) from the terrestrial organism Aspergillus versicolor NRRL 35600 along with a new alkaloid, (+)-versicolamide B (9), which possesses a novel antirelationship between C-21-C-22 and C-17-N-13 in the bicyclo[2.2.2]diazaoctane ring system. 6 Based on this presumption, the presence of (−)-versicolamide B (10) was predicted to be a metabolite in our marine-derived Aspergillus sp. (Figure 2). In the continuing search for notoamide congeners, we finally succeeded in isolating 10 along with new notoamides L-N (11-13) (Figure 1). Here we report their structures and suggest another possible biosynthetic pathway that accommodates the biogenesis of the respective antipodes of notoamide B and versicolamide B.The fractions rich in indole alkaloids, which derived from the EtOH extract of the fungal culture, 2 was further purified by HPLC to afford (−)-versicolamide B (10) and notoamides L-N (11-13).The HRFABMS of 10 showed the molecular formula C 26 H 29 N 3 O 4 . The 1 H NMR spectrum of 10 (Table S1) was superimposable on that of (+)-versicolamide B (9) and revealed that the structure and relative stereochemistry was the same as that of 9. The specific rotation of 10 (−22°) was of the opposite sign to that of 9 (+26°), and the CD spectrum of 10 ( Figure S6) was also opposite to that of 9. These data conclusively reveal that 10 is the antipodal (−)-versicolamide B, and that 9 and 10 are the third pair of antipodal natural metabolites isolated from the closely-related Aspergillus fungi.The molecular formula of notoamide L (11), C 25 H 29 N 3 O 4 , was established by high-resolution FABMS, and the 1 H NMR spectrum (Table S2) showed three singlet methyl signals at δ 1.39, 1.40, and 1.64. In contrast to other prenylated indole alkaloids, one singlet methy...

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Two new imidazole alkaloids, naamidines H ( 1) and I ( 2), were isolated from the marine sponge Leucetta chagosensis, collected in North Sulawesi, Indonesia. The compounds ( 1 and 2) showed cytotoxicity against HeLa cells with IC50 values of 5.6 and 15 microg/mL, respectively.

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