A concise route to the pregnane X receptor (PXR) agonist solomonsterol B, a natural product isolated from the marine sponge Theonella swinhoei, has been developed starting from commercially available hyodeoxycholic acid. The synthesis features a one-carbon side chain degradation and the refunctionalization of the A and B rings to install the desired trans junction and the two hydroxy groups at C2 and C3 in a trans relationship. The protocol proceeded with good yields (10 % over 13 steps), also allowing the preparation of a side chain-modified derivative useful for a preliminary structure-activity relationship on PXR. The pharmacological characterization of solomonsterol B demonstrated that this compound was a PXR agonist in a transactivation assay, and when it was incubated with liver cells, it increased the expression of PXR-regulated genes. These data support the development of sponge steroids as PXR ligands endowed with therapeutic potential.

The First Total Synthesis of Solomonsterol B, a Marine Pregnane X Receptor Agonist / Sepe, Valentina; Ummarino, Raffaella; D'Auria, MARIA VALERIA; Barbara, Renga; Stefano, Fiorucci; Zampella, Angela. - In: EUROPEAN JOURNAL OF ORGANIC CHEMISTRY. - ISSN 1434-193X. - 27:(2012), pp. 5187-5194. [10.1002/ejoc.201200619]

The First Total Synthesis of Solomonsterol B, a Marine Pregnane X Receptor Agonist

SEPE, VALENTINA;UMMARINO, RAFFAELLA;D'AURIA, MARIA VALERIA;ZAMPELLA, ANGELA
2012

Abstract

A concise route to the pregnane X receptor (PXR) agonist solomonsterol B, a natural product isolated from the marine sponge Theonella swinhoei, has been developed starting from commercially available hyodeoxycholic acid. The synthesis features a one-carbon side chain degradation and the refunctionalization of the A and B rings to install the desired trans junction and the two hydroxy groups at C2 and C3 in a trans relationship. The protocol proceeded with good yields (10 % over 13 steps), also allowing the preparation of a side chain-modified derivative useful for a preliminary structure-activity relationship on PXR. The pharmacological characterization of solomonsterol B demonstrated that this compound was a PXR agonist in a transactivation assay, and when it was incubated with liver cells, it increased the expression of PXR-regulated genes. These data support the development of sponge steroids as PXR ligands endowed with therapeutic potential.
2012
The First Total Synthesis of Solomonsterol B, a Marine Pregnane X Receptor Agonist / Sepe, Valentina; Ummarino, Raffaella; D'Auria, MARIA VALERIA; Barbara, Renga; Stefano, Fiorucci; Zampella, Angela. - In: EUROPEAN JOURNAL OF ORGANIC CHEMISTRY. - ISSN 1434-193X. - 27:(2012), pp. 5187-5194. [10.1002/ejoc.201200619]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/505129
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