Stereochemical determination and bioactivity assessment of (S)-(+)-curcuphenol dimers isolated from the marine sponge Didiscus aceratus and synthesized through laccase biocatalysis.
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.
Cichewicz
Robert H
RH
Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, USA.
Clifford
Laura J
LJ
Lassen
Peter R
PR
Cao
Xiaolin
X
Freedman
Teresa B
TB
Nafie
Laurence A
LA
Deschamps
Joshua D
JD
Kenyon
Victor A
VA
Flanary
Jocelyn R
JR
Holman
Theodore R
TR
Crews
Phillip
P
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
D016859:Lipoxygenase Inhibitors; D012717:Sesquiterpenes; C054389:curcuphenol; D042845:Laccase