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Rapid hydrolysis of bile acid conjugates using microwaves: Retention of absolute stereochemistry in the hydrolysis of (25R) 3α,7α,12α-trihydroxy-5β-cholestan-26-oyltaurine

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Lipids

Abstract

In recent years, defects of bile acid synthesis caused by disorders of peroxisome biogenesis have led to increased interest in C27 bile acids. In humans, while the majority of bile acids are C24 carboxylic acids, the presence of increased concentrations of C27 bile acids and their metabolites in hereditary diseases associated with peroxisomal dysfunction can serve as a useful marker for the intensity of the metabolic disorder. Our present studies describe an efficient method for the rapid hydrolysis of C27 and C24 bile acid conjugates using a commercial microwave oven. The advantages of this method include freedom from racemization, minimal activation, mild reaction conditions, and the highly stereocontrolled nature of the reaction, thus allowing for free bile acid recovery in high yield. For example, when (25R) 3α,7α,12α-trihydroxy-5β-cholestan-26-oyl taurine, a major compound present in the bile of Alligator mississippiensis, was deconjugated with 4% NaOH/diethylene glycol or 1 M LiOH/propylene glycol in the microwave oven for 4–6 min, 3α,7α,12α-trihydroxy-5β-cholestan-26-oic acid (THCA) was obtained in 81% yield with retention of configuration at C-25. It is suggested that present studies will be helpful in delineating the absolute stereochemistry of 3α,7α,12α-trihydroxy-5β-cholestanoyl-CoA oxidase, the peroxisomal enzyme that catalyzes the first step in the oxidation of THCA.

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Abbreviations

CGH:

cholylglycine hydrolase (E.C. 3.5.1.24)

FAB-MS:

fast atom bombardment-mass spectrometry

GLC:

gas-liquid chromatography

MW:

microwave oven

THCA:

3α,7α,12α-trihydroxy-5β-cholestan-26-oyl-taurine acid

TLC:

thin-layer chromatography

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Authors and Affiliations

  1. Medical Service, Department of Veterans Affairs Medical Center, 07018, East Orange, New Jersey

    Bishambar Dayal & Norman H. Ertel

  2. Department of Medicine, UMDNJ-New Jersey Medical School, 07103, Newark, New Jersey

    Bishambar Dayal

  3. Robert Wood Johnson Medical School, New Brunswick, New Jersey

    Norman H. Ertel

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  1. Bishambar Dayal
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Correspondence to Bishambar Dayal.

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Dayal, B., Ertel, N.H. Rapid hydrolysis of bile acid conjugates using microwaves: Retention of absolute stereochemistry in the hydrolysis of (25R) 3α,7α,12α-trihydroxy-5β-cholestan-26-oyltaurine. Lipids 33, 333–338 (1998). https://doi.org/10.1007/s11745-998-0213-y

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  • DOI: https://doi.org/10.1007/s11745-998-0213-y

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