Synthesis of 1β-hydroxydeoxycholic acid in H-2 and unlabeled forms.
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 [D4]deoxycholic acid, respectively.
Cardiovascular and Metabolic Diseases Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Mölndal, Sweden.
Martin A
0000-0002-2640-8464
MA
Hayes
Discovery Sciences, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Cambridgeshire, UK.
Ieuan
I
Roberts
Respiratory, Inflammation & Autoimmunity, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Mölndal, Sweden.
Gunnar
G
Grönberg
WuXi AppTec, Shanghai, China.
Kexin
K
Lv
WuXi AppTec, Shanghai, China.
Baorui
B
Lin
Pharmaceutical Sciences Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Mölndal, Sweden.
Jonas
J
Bergare
Pharmaceutical Sciences Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Mölndal, Sweden.
Charles S
0000-0001-7434-8307
CS
Elmore
D060326:Chemistry Techniques, Synthetic; D002635:Chenodeoxycholic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D003903:Deuterium / Q000737:chemistry*; D007553:Isotope Labeling
C092209:1-hydroxychenodeoxycholic acid; D002635:Chenodeoxycholic Acid; D003903:Deuterium; D051544:Cytochrome P-450 CYP3A
Cytochrome P450 3A4; NMR; Steroid; biocatalysis