Eusynstyelamides A, B, and C, nNOS Inhibitors, from the Ascidian Eusynstyela latericius

Abstract

Eusynstyelamides A-C (1-3) were isolated from the Great Barrier Reef ascidian Eusynstyela latericius, together with the known metabolites homarine and trigonelline. The structures of 1-3, with relative configurations, were elucidated by interpretation of their spectroscopic data (NMR, MS, UV, IR, and CD). The NMR data of 1 were found to be virtually identical to that reported for eusynstyelamide (4), isolated from E. misakiensis, indicating that a revision of the structure of 4 is needed. Eusynstyelamides A-C exhibited inhibitory activity against neuronal nitric oxide synthase (nNOS), with IC(50) values of 41.7, 4.3, and 5.8 microM, respectively, whereas they were found to be nontoxic toward the three human tumor cell lines MCF-7 (breast), SF-268 (CNS), and H-460 (lung). Compounds 1 and 2 displayed mild inhibitory activity toward Staphylococcus aureus (IC(50) 5.6 and 6.5 mM, respectively) and mild inhibitory activity toward the C(4) plant regulatory enzyme pyruvate phosphate dikinase (PPDK) (IC(50) values of 19 and 20 mM, respectively).

Marine Bi-, Bis-, and Trisindole Alkaloids

“…The 2-pyrrolidine-containing anchinopeptolide D (163), previously synthesized by aldol dimerization, prompted Tapiolas et al to propose a similar biogenesis for 159-161 (Scheme 1.28). 86 Accordingly, heating a single enantiomer of any one of the eusynstyelamides A-C with KOH in 1:1 THF/MeOH yielded an equilibrium mixture of all three isomers, suggesting that eusynstyelamide A-C may be isolation artifacts. 86 However, a repetition of the methanolic extraction of E. latericius was found to contain only 159, which remained the only enantiomer present after refluxing in methanol for 1 h. Additionally, after prolonged storage of 159-161 in methanol, they appeared to remain present in the same ratio as originally discovered, with no evidence of equilibration.…”

“…86 Accordingly, heating a single enantiomer of any one of the eusynstyelamides A-C with KOH in 1:1 THF/MeOH yielded an equilibrium mixture of all three isomers, suggesting that eusynstyelamide A-C may be isolation artifacts. 86 However, a repetition of the methanolic extraction of E. latericius was found to contain only 159, which remained the only enantiomer present after refluxing in methanol for 1 h. Additionally, after prolonged storage of 159-161 in methanol, they appeared to remain present in the same ratio as originally discovered, with no evidence of equilibration. 86 An enantiomer of 160, ent-eusynstyelamide B (164), together with three new derivatives eusynstyelamides D-F (165-167) was isolated from the Arctic bryozoan Tegella cf.…”

“…85 dimers, eusynstyelamide A-C (159-161), were later isolated from the ascidian Eusynstyela latericius collected from the Great Barrier Reef 86 (Figure 1.13). While the determination of the absolute configuration of these three compounds was inconclusive, Tapiolas et al were satisfied that 159-161 had not been isolated as racemates 86 and further noted that NMR, MS, and IR spectral data of the originally reported 158 85 were almost identical with those of 159, with an opposite specific rotation, suggesting that the antipode of 159 was a more accurate structural representation of 158. ent-eusynstyelamide A (162) 86 (Figure 1.13). This revised structure and name will be retained throughout this review.…”

A novel synthesis route to furo[3,2-a]carbazole

“…Compounds containing carbazole core 11 structures are of great pharmaceutical interest due to their potent 12 biological activity and medicinal significance. Consequently, many 13 synthetic protocols have been developed to access these frame-14…”

“…Conditions for non-enzymatic transamination were 42 developed [7,8] and played an important role in the synthesis of 43 natural products [9,10]. Meanwhile, although indole 3-pyruvic 44 acid and its derivatives are key intermediates in the biosynthetic 45 route of several indole alkaloids such as rebeccamycin [11,12] and 46 eusynstyelamides A-C [13]. To the best of our knowledge, these 47 biosynthetic indications and fragment convenience were rarely 48 involved in the process of developing synthetic strategies for 49 carbazoles.…”