PPAR Modulating Polyketides from a Chinese Plakortis simplex and Clues on the Origin of Their Chemodiversity

Abstract

Fifteen polyketides, including the first hydroxylated plakortone (12) and plakdiepoxide (15), the first polyketide to embed a vicinal diepoxide, have been isolated from the Chinese sponge Plakortis simplex. The structures of the new metabolites were elucidated by analysis of spectroscopic data, Mosher's derivatization, and DFT computational calculations. The reactivity of the major endoperoxide of this sponge was investigated, suggesting that furan, furanylidene, and plakilactone derivatives, well-known classes of natural products, could actually be chemical degradation products. Plakdiepoxide is a potent and selective modulator of peroxisome proliferator-activated receptor (PPAR)-γ, while the diunsaturated C12 fatty acid monotriajaponide (13) activates both PPAR-α and PPAR-γ, a dual activity of potential great importance for the treatment of metabolic disorders.

3,5‐Dimethylorsellinic Acid Derived Meroterpenoids from Eupenicillium sp. 6A‐9, a Fungus Isolated from the Marine Sponge Plakortis simplex

“…However, our previous chemical investigations of the marine sponge Plakortis simplex did not find this kind of meroterpenoid. [33][34][35][36][37][38] It is interesting that almost at the same time, Qi et al also isolated several similar 3,5-dimethylorsellinic acid derived meroterpenoids, of which chrysogenolide H is the C-9 epimer of 1, but from a Penicillium species derived from a terrestrial plant, Huperzia serrata. [13] Although the origin of marine fungal strains has been the subject of controversy, with the extreme positions from being true symbionts to being contaminants washed into the sea from terrestrial environments, fungi from marine habitats are a prospective reservoir of new biologically active natural products.…”

Chemistry and Selective Tumor Cell Growth Inhibitory Activity of Polyketides from the South China Sea Sponge Plakortis sp.

“…The HRESIMS and NMR spectroscopic data of 2 reveal the identical structure of plakortone Q, recently obtained from the Chinese sponge Plakortis simplex [13]. However, the absolute configuration of C-8 in the alkyl chain was not determined in the literature.…”

“…The diethyl ether soluble portion of the acetone extract was subjected to repeated column chromatography on silica gel, Sephadex LH-20, and RP-HPLC to afford nine polyketides 1 – 9 . By extensive spectroscopic analysis combined with careful comparison with the reported data, the structures of the known compounds were determined as lactone derivatives plakortone Q ( 2 ) [13], simplextones A-C ( 3 – 5 ) [11,12], peroxide derivatives methyl (3 S ,6 R ,8 S )-4,6-diethyl-3,6-epidioxy-8-methyldodeca-4-enoate ( 6 ) [16] and haterumadioxin B ( 7 ) [38], furanylidene derivatives 8 [15] and 9 [40,41]. Plakortone Q ( 2 ) and simplextones A-C ( 3 – 5 ) were once reported from the South China Sea sponge P. simplex , while peroxide derivatives 6 and 7 were previously obtained from P. angulospiculatus and P. lita , respectively.…”

“…This family of polyketides are commonly characterized with a cyclic peroxide [2,3,4,5,6], a penta-lactone [7,8,9,10,11,12,13], or a furano ring [14,15,16] as core structure, and a flexible alkyl chain. A small number of polyketides have a simple linear structure [17,18].…”

“…In the course of our continuing search for novel and bioactive secondary metabolites from marine invertebrates [36,37], we reinvestigated the marine sponge Plakortis sp., collected from the South China Sea, leading to the isolation of a new polyketide, simplextone E ( 1 ), together with eight known analogues ( 2 – 9 ) (Figure 1), namely lactone derivatives plakortone Q ( 2 ) [13], simplextones A-C ( 3 – 5 ) [11,12], peroxide derivatives methyl (3 S ,6 R ,8 S )-4,6-diethyl-3,6-epidioxy-8-methyldodeca-4-enoate ( 6 ) [16], haterumadioxin B ( 7 ) [38], furanylidene derivatives spongosoritin A ( 8 ) [15,39], and 6-desmethyl-6-ethylspongosoritin A ( 9 ) [40,41]. The structures of these compounds were elucidated by extensive spectroscopic analysis and compared with the reported data.…”