Pyrrole Derivatives and Diterpene Alkaloids from the South China Sea Sponge Agelas nakamurai

Abstract

Two pairs of new non-brominated racematic pyrrole derivatives, (±)-nakamurine D (1) and (±)-nakamurine E (2), two new diterpene alkaloids, isoagelasine C (16) and isoagelasidine B (21), together with 13 known pyrrole derivatives ((±)-3 - 15), five known diterpene alkaloids (17 - 20, 22) were isolated from the South China Sea sponge Agelas nakamurai. The racemic mixtures, compounds 1 - 4, were resolved into four pairs of enantiomers, (+)-1 and (-)-1, (+)-2 and (-)-2, (+)-3 and (-)-3, and (+)-4 and (-)-4, by chiral HPLC. The structures and absolute configurations were elucidated on the basis of comprehensive spectroscopic analyses, quantum chemical calculations, quantitative measurements of molar rotations, application of van't Hoff's principle of optical superposition, and comparison with the literature data. The NMR and MS data of compound 3 are reported for the first time, as the structure was listed in SciFinder Scholar with no associated reference. These non-brominated pyrrole derivatives were found in this species for the first time. Compound 18 showed valuable cytotoxicities against HL-60, K562, and HCT-116 cell lines with IC values of 12.4, 16.0, and 19.8 μm, respectively. Compounds 16 - 19, 21, and 22 showed potent antifungal activities against Candida albicans with MIC values ranging from 0.59 to 4.69 μg/ml. Compounds 16 - 19 exhibited moderate antibacterial activities against Proteusbacillus vulgaris (MIC values ranging from 9.38 to 18.75 μg/ml).

Marine natural products

“…These compounds are the rst terpene/polyketide/ pyridine hybrids known. 452 Adenine-containing meroditerpenoids 1132-1134 were reported from two species of Agelas collected in the South China sea, 409,429 The relative congurations between these two unprecedented tetracyclo-tetradecane compounds suggest they are formed from a photochemical [2 + 2] cycloaddition reaction of a dolabellane skeleton. The absolute conguration of both compounds was solved by X-ray crystallography.…”

Halimane diterpenoids: sources, structures, nomenclature and biological activities

“…7, Table S1 †); all of them were isolated from marine organisms. 46,47,75,83,128,[133][134][135] A series of diterpene glycerides involved in chemical defense of nudibranchs has been isolated from the Antarctic nudibranch Austrodoris kerguelenensis. Among them 95, 97 and 98 are included.…”

“…Compounds of this type have been isolated from plants of the families Euphorbiaceae, 44,78,105,107,109,[111][112][113][114][136][137][138][139][140][141][142][143][144][145][146][147][148][149][150][151] Compositae, 45 Annonaceae, 122 Lamiaceae, 91 Jungermanniaceae, 152,153 Asteraceae, 76 and Meliaceae, 154 and in sponges of genus Agelas. 79,135 Among them, chettaphanin II (102) 111 is found. It was isolated from Adenochlaena siamensis, which, along with chettaphanin I (38), are the two rst known halimanes.…”

A Decade of Antifungal Leads from Natural Products: 2010–2019

“…Among metabolites isolated from the marine sponge Agelas, two new diterpene alkaloids from Agelas citrina, agelasidine E and F (52,53), were reported to have MIC values of 8 and 4 μg/mL, respectively, against C. albicans [42]. Isoagelasine C (54), isolated from Agelas nakamurai, had an MIC value of 4.7 μg/mL against C. albicans [43]. Ageloxime B (55), isolated from Agelas mauritiana, had an IC50 value of 5.0 μg/mL against C. neoformans as well as antibacterial activity [44].…”