title: Stereochemical determination and bioactivity assessment of (S)-(+)-curcuphenol dimers isolated from the marine sponge Didiscus aceratus and synthesized through laccase biocatalysis.
abstract: Electrospray ionization mass spectrometry-guided isolation of extracts from Didiscus aceratus led to the discovery of several new derivatives of the bioactive bisabolene-type sponge metabolite (S)-(+)-curcuphenol (1). The compounds obtained by this method included a mixture of known (2) and new (3) dihydroxylated analogs as well as a novel family of dimeric derivatives, dicurcuphenols A-E (4-8), and dicurcuphenol ether F (9). Dimers 4-9 were also subsequently obtained through a hemisynthetic method in which 1 was incubated with the enzyme laccase. Atropisomeric dimers 5 and 6 were subjected to vibrational circular dichroism analysis thereby establishing their absolute biaryl axial chirality as P and M, respectively. In contrast to 1, metabolites 2-9 exhibited weak or no cytotoxic or lipoxygenase inhibitory effects.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Cichewicz
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Clifford
authors.forename: Peter R
authors.initials: PR
authors.lastname: Lassen
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Cao
authors.forename: Teresa B
authors.initials: TB
authors.lastname: Freedman
authors.forename: Laurence A
authors.initials: LA
authors.lastname: Nafie
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Deschamps
authors.forename: Victor A
authors.initials: VA
authors.lastname: Kenyon
authors.forename: Jocelyn R
authors.initials: JR
authors.lastname: Flanary
authors.forename: Theodore R
authors.initials: TR
authors.lastname: Holman
authors.forename: Phillip
authors.initials: P
authors.lastname: Crews
mesh_terms: D000818:Animals; D002384:Catalysis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D019281:Dimerization; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D042845:Laccase / Q000737:chemistry*; D016859:Lipoxygenase Inhibitors; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D008968:Molecular Conformation; D011161:Porifera / Q000737:chemistry*; D012717:Sesquiterpenes / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D016859:Lipoxygenase Inhibitors; D012717:Sesquiterpenes; C054389:curcuphenol; D042845:Laccase