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
收藏
页码：5187 / 5194
页数：8
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