Hayes Martin A, Roberts Ieuan, Grönberg Gunnar, Lv Kexin, Lin Baorui, Bergare Jonas, Elmore Charles S
Cardiovascular and Metabolic Diseases Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Mölndal, Sweden.
Discovery Sciences, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Cambridgeshire, UK.
J Labelled Comp Radiopharm. 2017 Apr;60(4):221-229. doi: 10.1002/jlcr.3495. Epub 2017 Mar 20.
1β-hydroxydeoxycholic acid in unlabeled and stable isotope labeled forms was required for use as a biomarker for Cytochrome P450 3A4/5 activity. A lengthy synthesis was undertaken to deliver the unlabeled compound and in the process, to develop a route to the deuterium labeled compound. The synthesis of the unlabeled compound was completed but in a very low yield. Concurrent with the synthetic approach, a biosynthetic route was pursued and this approach proved to be much more rapid and afforded the compound in both unlabeled and deuterium labeled forms in a 1-step oxidation from deoxycholic acid and [D ]deoxycholic acid, respectively.
未标记和稳定同位素标记形式的1β-羟基脱氧胆酸被用作细胞色素P450 3A4/5活性的生物标志物。进行了冗长的合成以制备未标记的化合物，并在此过程中开发了一条通往氘标记化合物的路线。未标记化合物的合成完成了，但产率非常低。在采用合成方法的同时，还探索了一条生物合成路线，事实证明这条路线要快得多，并且分别从脱氧胆酸和[D]脱氧胆酸通过一步氧化反应，以未标记和氘标记形式得到了该化合物。
