Quantitative NMR-derived interproton distances combined with quantum mechanical calculations of 13C chemical shifts in the stereochemical determination of conicasterol F, a nuclear receptor ligand from Theonella swinhoei.
Here we report the first application of combined accurate ROE-distance analysis with DFT calculations of NMR chemical shifts to achieve the relative configuration assignment of a marine natural product, conicasterol F, a new polyhydroxylated steroid isolated from the marine sponge Theonella swinhoei. We demonstrate the substantial advantages of this combined approach as a tool for structural studies of natural products, providing a powerful alternative to, or information to underpin, total synthesis when more classical NMR data analysis fails to provide unequivocal results. In this paper, we also describe the isolation and structure elucidation of conicasterol F and its 24-ethyl derivative, theonellasterol I, and their pharmacological evaluation as human nuclear receptor modulators.
Dipartimento di Scienze Farmaceutiche e Biomediche, Università di Salerno, via Ponte don Melillo, 84084 Fisciano (SA), Italy.
Maria Giovanna
MG
Chini
Catharine R
CR
Jones
Angela
A
Zampella
Maria Valeria
MV
D'Auria
Barbara
B
Renga
Stefano
S
Fiorucci
Craig P
CP
Butts
Giuseppe
G
Bifulco
D000818:Animals; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D056945:Hep G2 Cells; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D000077297:Pregnane X Receptor; D011522:Protons; D011789:Quantum Theory; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism; D013237:Stereoisomerism; D047232:Theonella / Q000737:chemistry*
D008024:Ligands; D000077297:Pregnane X Receptor; D011522:Protons; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; C098158:conicasterol; D002784:Cholesterol