The structures and cytotoxic properties of polyketide peroxides from a Plakortis sponge.
A morphologically distinct Fijian sponge, Plakortis sp., has yielded two new peroxides, plakortolide E [5] and plakoric acid [12]. After standing for approximately one year, plakortolide E rearranged to plakortolide ether [10]. The structures of plakortolide E [5] and plakortolide ether [10] were established from 2D nmr data and by analogy to a known compound, plakortolide [3]. The stereochemistry of the bicyclic ring substituents of 5 was established using nOe and NOESY nmr data along with comparisons to 3. The absolute stereochemistry at the three chiral sites of 5 was assigned by preparing acyclic compounds 6-9, and both 8 and 9 were investigated using the modified Mosher's method. This represents the first absolute stereochemistry determination for a sponge-derived polyketide peroxide. The characterization of plakoric acid [12] was based on spectral analogies to known polyketides such as plakortin. Plakortolide E [5] exhibited selective potency against the melanoma and breast tumor cell lines in the in vitro 60-cell line panel of the National Cancer Institute.
Varoglu
M
M
Department of Chemistry and Biochemistry, University of California, Santa Cruz 95064.
Peters
B M
BM
Crews
P
P
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D004146:Dioxanes / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011161:Porifera / Q000737:chemistry*; D011422:Propionates / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004146:Dioxanes; D011422:Propionates; C093754:plakoric acid; C093753:plakortolide E; D015107:4-Butyrolactone