Synthesis of hyocholic acid and its derivatization with sodium periodate to distinguish it from cholic acid by mass spectrometry.

Autor: Ho TM; Department of Chemistry, The University of Texas at San Antonio (UTSA), San Antonio, TX 78249, United States., Arman HD; Department of Chemistry, The University of Texas at San Antonio (UTSA), San Antonio, TX 78249, United States., Yoshimoto FK; Department of Chemistry, The University of Texas at San Antonio (UTSA), San Antonio, TX 78249, United States. Electronic address: francis.yoshimoto@utsa.edu.
Jazyk: angličtina
Zdroj: Steroids [Steroids] 2023 Sep; Vol. 197, pp. 109260. Date of Electronic Publication: 2023 Jun 17.
DOI: 10.1016/j.steroids.2023.109260
Abstrakt: Low concentrations of hyocholic acid in human serum has been linked to diabetes. Due to its important role in human health, we were interested in synthesizing hyocholic acid to explore potential biochemical properties of this bile acid. Here, a synthesis of hyocholic acid is reported from chenodeoxycholic acid. The key step was a Rubottom oxidation of a silyl enol ether intermediate to directly incorporate the oxygen at C6. Furthermore, the synthesized hyocholic acid product was treated with NaIO 4 to cleave the C6-C7 bond to yield a hemiacetal at C6. This CC bond cleavage reaction using NaIO 4 was used to develop an ultra-performance liquid chromatography mass spectrometry method to distinguish between a 1 to 1 mixture of hyocholic acid and cholic acid (a 12α-hydroxylated bile acid), two bile acid regioisomers with identical masses. Upon treatment of the mixture with NaIO 4 , hyocholic acid was selectively cleaved in the B ring (C6-C7 bond) to yield the hemiacetal that formed between the C3-hydroxy and the C6-aldehyde moiety with an m/z 405 while cholic acid remained intact with an m/z 407 in the negative electrospray ionization mode. Subsequently, a commercially available ox bile extract was treated with NaIO 4 to detect bile acid derivatives by mass spectrometry. Two possible hyocholic acid derivatives conjugated to serine and gamma-glutamic semialdehyde were detected in electrospray ionization positive mode, which oxidatively cleaved with NaIO 4 (m/z 496 and 522 to m/z 494 and 520, respectively).
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: