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

被引：17

作者：

Sepe, Valentina ^{[1
]}

Ummarino, Raffaella ^{[1
]}

D'Auria, Maria Valeria ^{[1
]}

Renga, Barbara ^{[2
]}

Fiorucci, Stefano ^{[2
]}

Zampella, Angela ^{[1
]}

机构：

[1] Univ Naples Federico II, Dipartimento Chim Sostanze Nat, I-80131 Naples, Italy

[2] Univ Perugia, Dipartimento Med Clin & Sperimentale, Nuova Fac Med Chirurg, I-06132 Perugia, Italy

来源：

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY | 2012年 / 2012卷 / 27期

关键词：

Total synthesis; Natural products; Steroids; Structure-activity relationships; NF-KAPPA-B; INFLAMMATORY-BOWEL-DISEASE; BILE-ACID; NORURSODEOXYCHOLIC ACID; CYTOCHROME-P-450; 3A4; XENOBIOTIC RECEPTOR; THEONELLA-SWINHOEI; NATURAL LIGANDS; SIDE-CHAIN; METABOLITES;

D O I：

10.1002/ejoc.201200619

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

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 structureactivity 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.

引用

页码：5187 / 5194

页数：8

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