Department of Diabetes, Endocrinology and Metabolism, The Beckman Research Institute at The City of Hope National Medical Center, Duarte, CA 91010, USA.
Steroids. 2012 Nov;77(13):1335-8. doi: 10.1016/j.steroids.2012.09.002. Epub 2012 Sep 21.
The active, potent, and selective Farnesoid X Receptor (FXR) agonist 6α-ethylchenodeoxycholic acid (6ECDCA) has been synthesized in improved yield compared to the published methodologies. The synthesis employed selective oxidation of one of the two hydroxyls of the readily-available starting material chenodeoxycholic acid (CDCA) as a key step. After protection of the remaining hydroxyl, LDA/HMPA/EtI/PPTS provided an efficient deprotonation/ethylation/deprotection sequence. The two synthetic improvements that allow a productive yield are the use of PCC in the oxidation step, and the use of HMPA/ethyl iodide in the stereoselective alkylation step. This synthesis offers an economical and efficient strategy which provides a simple and cost-effective procedure for potential large-scale production of this promising FXR agonist, which is a research tool and potential drug substance of current interest.
与已发表的方法相比，合成了产率得到提高的活性、有效且选择性的法尼醇 X 受体（FXR）激动剂 6α-乙基鹅去氧胆酸（6ECDCA）。该合成采用选择性氧化易得起始原料鹅去氧胆酸（CDCA）的两个羟基之一作为关键步骤。在保护剩余的羟基后，LDA/HMPA/EtI/PPTS 提供了有效的去质子化/乙基化/脱保护序列。允许高产率的两个合成改进是在氧化步骤中使用 PCC，以及在立体选择性烷基化步骤中使用 HMPA/乙基碘化物。该合成提供了一种经济高效的策略，为这种有前途的 FXR 激动剂的潜在大规模生产提供了一种简单且具有成本效益的方法，该激动剂是当前研究工具和潜在药物的研究工具。
