Synthetic method of 13C marked glycocholic acid

Abstract

The invention relates to a synthetic method of 13C marked glycocholic acid, and the method comprises the following steps: under the protection of nitrogen, 13C marked glycine benzyl ester hydrochloride and cholic acid are mixed and dissolved in a polar solvent, then coupling reagent is added, the reaction temperature is controlled between minus 20 and 150DEG C, the reaction time is 0.1 to 120h, and then the product is obtained after separation and purification by a silica gel column. The method adopts the coupling agent to synthesize the 13C marked glycocholic acid, the yield of the glycocholic acid can achieve above 80 percent, the abundance of 13C can achieve 99atm%, the optical purity can achieve 98 percent, and the chemical purity can achieve 98 percent. The obtained 13C marked glycocholic acid can be used as medical diagnosis reagent and can be used for enterohepatic circulation of the cholic acid, overgrowth of intestinal bacteria, activity evaluation of bacterial metabolism andthe like.

Description

technical field [0001] The present invention relates to a kind of synthetic method of glycocholic acid, especially relate to a kind of 13 Synthetic method of C-labeled glycocholic acid. Background technique [0002] 13 C-labeled glycocholic acid is a medical diagnostic reagent that can be used for the enterohepatic circulation of bile acid, the overgrowth of intestinal bacteria, the evaluation of bacterial metabolic activity, etc. (J.S. Sukhodolski, C.G. Ruaukos, J.M. Na et al., Assessing the metabolic activity of bacteria in the canine small intestine 13 C-glycocholic acid blood test progress, Canadian Journal of Veterinary Research (Canadian J. Veterinary Research), 2005, 69: 313-317; N.M. Solomon, D.A. Scheele, J.B. Wagonfield et al., stable isotopes 13 Application of C-labeled glycocholic acid breath test in the diagnosis of small intestinal bacterial overgrowth and ileal dysfunction, Journal of Medical Clinical Experiments (J.Lab.Clin.Med.) 1977, 90: 431-439; C.E. Ki...

AI Technical Summary

Problems solved by technology

There are two problems in this method. One is that the selectivity of the EEDQ condensation reagent is not high enough. The carboxyl group on the cholic acid can react with the amino group on the glycine ethyl ester, and can also react with the hydroxyl group on another cholic acid molecule (note: cholic acid There are 3 hydroxyl groups in the molecule), and the by-product bis-cholic acid or polycholic acid is generated; the second is that the selective hydrolysis of ethyl glycocholate hydrolysis is not easy to control, and hydrolysis at the amide group will occur to generate cholic acid and glycine ethyl ester or glycine