Polyhydroxylated Steroids and Other Constituents of the Soft Coral Nephthea chabroli

Abstract

Soft corals contain a variety of bioactive compounds such as diterpenes, sesquiterpenes, and steroids. 1) In the course of our search for biologically active substances from marine organisms, 2-4) a collection of the soft coral Nephthea chabroli was obtained from the South China Sea, and from this collection, cembrane diterpenes and norditerpenes (chabrolols A-C) were obtained.2) Another chemical constituent, lemnabourside, was found to show anti-proliferative and 5a-reductase inhibitory effect on human prostate cancer cells. 3)In the literature, secondary metabolites including benzoquinone derivatives, sesquiterpenes, and sterols have been reported from Nephthea chabroli. [5][6][7][8][9] In the present paper, we report the isolation of eight sterols (1-8), a diterpene glycoside (9), a ceramide (10), a quinoline (11), and fatty acid derivatives (12-13). Of these constituents, 6 and 8 are new structures.Compounds 1-6 displayed characteristic spectral features of 19-hydroxylated steroids, 10,11) showing in their NMR spectra a pair of methylene proton doublets at about d H 3.7 (1H, Jϭ12 Hz) and 3.9 (1H, Jϭ12 Hz), as well as a methylene carbon signal at d C 63.2 (t). The structures of 1-5 were determined to be 24-methylcholesta-5,24(28)-diene-3b,19-diol (1), 12,13) 24-methylcholesta-5,24(28)-diene3b,7b,19-triol (2), 12,13) 24-methyl-7b-acetoxycholesta-5,24(28)-diene-3b,19-diol (3), 12,13) 24-methylcholest-24(28)-ene-3b,5a,6b,19-tetraol (4), 12,13) and 24-methyl-7-oxocholesta-5,24(28)-diene-3b,19-diol (5).12) The structural identities of these compounds were established by comparing the physical and spectroscopic data with literature values.Compound 6 ) and a terminal methylene (1640, 900 cm Ϫ1 ). The presence of a primary hydroxyl and two secondary hydroxyl groups was revealed by 1 H-and With the assistance of computer-aided molecular modeling (MOPAC molecular modeling program), the energy-minimized stereostructure of 6 showed the dihedral angle (j) between H 11 -C 11 -C 12 -H 12 to be 37.7°, corresponding to a coupling constant of 2-5 Hz as estimated from the Karplus correlation graph. Given a coupling constant of 4 Hz for H-12, b-orientation of 12-H was assumed. Indeed, the nuclear Overhauser effect spectroscopy (NOESY) spectrum displayed correlation signals between H 12 /H 18 as well as between H 11 /H 12 . These NOE results were in support of the stereochemical assignment. Hence, all available data indicated a structure of 24-methylcholesta-9(11),24(28)-diene-3b,12a,19-triol for 6.Compound 7 was determined to be 24-methylcholesta-5,24(28)-dien-3b-ol by interpretation of its spectroscopic data and comparison with literature values. Polyhydroxylated steroids and other metabolites were isolated from the soft coral Nephthea chabroli collected in South China Sea. The structures of two new compounds were determined to be 24-methylcholesta-9(11), 24(28)-diene-3b b,12a a,19-triol and 4a a-methyl-3b b,14b b-dihydroxy-5a a-ergost-24(28)-en-23-one on the basis of spectroscopic analysis. Cytotoxic activities of the po...

Secondary Metabolites from the South China Sea Invertebrates: Chemistry and Biological Activity

“…Other two analogues, compounds 510 and 515, demonstrated moderate and selective cytotoxic activity against HT-29, A549 or P-388 cells [127]. In the bioassay against the LNCaP carcinoma cells, compounds 505 and 509 both exhibited weak cytotoxic activity, while 506, 508, 514, and 517 were inactive [120]. Interestingly, steroid 512 showed strong anti-inflammatory effects by inhibiting the release of inflammation factors such as prostaglandin E 2 , decreasing production of malondialdehyde, and enhancing the stability of membranes [217].…”

“…Cladiella sp. produced two steroids with the pregnane framework (467, 468), along with 24-methylene-5-ene-3β-ol (469) [97] which also commonly appeared in N. chabroli [120], Sinularia gyrosa [102], and Sinularia gibberosa [206]. A series of pregnane analogues were also obtained from species of the genus Scleronephthya (470-475) Polyoxygenated steroids occur commonly in soft corals.…”

“…Twelve of the thirteen analogues discovered so far (504-515) were scattered in almost all of the ten studied species except N. pacifica [120,127,[212][213][214][215][216][217][218][219][220][221][222] (Table 2). Compound 511 has repeatedly been isolated from Sinularia inexplicita [26] whereas compound 504 has also been found in L. arboreum where the additional 19-hydroxy steroid 516 was also produced [223].…”

“…Compound 511 has repeatedly been isolated from Sinularia inexplicita [26] whereas compound 504 has also been found in L. arboreum where the additional 19-hydroxy steroid 516 was also produced [223]. In addition, a 4-methyl steroid (517) was obtained from N. chabroli [120], and a novel ergosterol derivative with both 27-methyl and 26-ethyl groups (518) was isolated from N. albida [224]. Several other steroids possessing longer sidechains with additional methyl or ethyl groups attached at positions C-23, C-24, or C-26 were discovered in Lobophytum sp.…”

“…Another notable group of metabolites are the sesquiterpene hydroquinones from Polyfibrospongia australis(117)(118)(119)(120)(121) …”