Improved synthesis of glycine, taurine and sulfate conjugated bile acids as reference compounds and internal standards for ESI–MS/MS urinary profiling of inborn errors of bile acid synthesis. (April 2017)

• Record Type: Journal Article
• Authors: Donazzolo, Elena; Gucciardi, Antonina; Mazzier, Daniela; Peggion, Cristina; Pirillo, Paola; Naturale, Mauro; Moretto, Alessandro; Giordano, Giuseppe
• Is Part Of: Chemistry and physics of lipids. Volume 204(2017)
• Page Start: 43
• Page End: 56
• Publication Date: 2017-04
• Subjects: EEDQ N-ethoxycarbonyl-2-ethoxy-1, 2-dihydroquinoline -- DEPC diethyl phosphorocyanidate -- DPPA diphenyl phosphoryl azide -- SO3-TEA sulfur trioxide-triethylamine complex -- SO3-TMA sulfur trioxide-trimethylamine complex -- SO3-DMA sulfur trioxide-N, N-dimethylaniline complex -- SO3-PY sulfur trioxide-pyridine complex -- CA cholic acid -- CDCA chenodeoxycholic acid -- DCA deoxycholic acid -- UDCA ursodeoxycholic acid -- LCA lithocholic acid -- GCA glycocholic acid -- GCDCA glycochenodeoxycholic acid -- GDCA glycodeoxycholic acid -- GUDCA glycoursodeoxycholic acid -- GLCA glycolithocholic acid -- TCA taurocholic acid -- TCDCA taurochenodeoxycholic acid -- TDCA taurodeoxycholic acid -- TUDCA tauroursodeoxycholic acid -- TLCA taurolithocholic acid -- eq equivalent -- TLC thin-layer chromatography -- EtOAc ethyl acetate -- Na2SO4 sodium sulfate -- KOH potassium hydroxide -- NaOH sodium hydroxide -- HCl hydrochloride acid -- MeOH methanol -- Et2O diethyl ether -- TFA trifluoroacetic acid -- MeCN acetonitrile -- HSD3B7 3β -hydroxysteroid-Δ5-C27-steroid dehydrogenase deficiency -- HRMS high resolution mass spectrometry; Bile acid sulfates synthesis -- Glycine conjugated synthesis -- Taurine conjugated synthesis -- ESI–MS/MS -- Inborn error defects -- Liver disease; Lipids -- Periodicals; Lipids -- Periodicals; Lipides -- Périodiques; Lipids; Periodicals; Electronic journals; 547.77
• DOI: 10.1016/j.chemphyslip.2017.03.004
• Languages: English
• ISSNs: 0009-3084

Abstract

Graphical abstract: Highlights: 30 bile acids conjugated with glycine, taurine and sulfate were synthesized. DEPC and DPPA were used as coupling reagents for glycine and taurine conjugation. SO3 -TEA complex was used as sulfating agent to synthesize BAs sulfate. All new compounds were characterized by NMR, IR and ESI–MS/MS. Synthesized BAs were used for diagnosis of liver diseases by ESI–MS/MS analysis. Abstract: Bile acid synthesis defects are rare genetic disorders characterized by a failure to produce normal bile acids (BAs), and by an accumulation of unusual and intermediary cholanoids. Measurements of cholanoids in urine samples by mass spectrometry are a gold standard for the diagnosis of these diseases. In this work improved methods for the chemical synthesis of 30 BAs conjugated with glycine, taurine and sulfate were developed. Diethyl phosphorocyanidate (DEPC) and diphenyl phosphoryl azide (DPPA) were used as coupling reagents for glycine and taurine conjugation. Sulfated BAs were obtained by sulfur trioxide-triethylamine complex (SO3 -TEA) as sulfating agent and thereafter conjugated with glycine and taurine. All products were characterized by NMR, IR spectroscopy and high resolution mass spectrometry (HRMS). The use of these compounds as internal standards allows an improved accuracy of both identification and quantification of urinary bile acids.