TY - JOUR
T1 - Chemical synthesis of the 3-sulfooxy-7-N-acetylglucosaminyl-24-amidated conjugates of 3β,7β-dihydroxy-5-cholen-24-oic acid, and related compounds
T2 - Unusual, major metabolites of bile acid in a patient with Niemann-Pick disease type C1
AU - Iida, Takashi
AU - Kakiyama, Genta
AU - Hibiya, Yohei
AU - Miyata, Shohei
AU - Inoue, Takehiko
AU - Ohno, Kohsaku
AU - Goto, Takaaki
AU - Mano, Nariyasu
AU - Goto, Junichi
AU - Nambara, Toshio
AU - Hofmann, Alan F.
N1 - Funding Information:
We would like to express our thanks to Shimadzu Co. for the LC/ESI-MS/MS measurements. This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Sciences, Sports, and Culture of Japan for 2004-2005 and Nihon University Multidisciplinary Research Grant for 2005–2006.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/1
Y1 - 2006/1
N2 - The chemical synthesis of 3β,7β-dihydroxy-5-cholen-24-oic acid, triply conjugated by sulfuric acid at C-3, by N-acetylglucosamine (GlcNAc) at C-7, and by glycine or taurine at C-24, is described. These are unusual, major metabolites of bile acid found to be excreted in the urine of a patient with Niemann-Pick disease type C1. Analogous double-conjugates of 3β-hydroxy-7-oxo-5-cholen-24-oic acid were also prepared. The principal reactions involved were: (1) β-d-N-acetylglucosaminidation at C-7 of methyl 3β-tert-butyldimethylsilyloxy (TBDMSi)-7β-hydroxy-5-cholen-24-oate with 2-acetamido-1α-chloro-1,2-dideoxy-3,4,6-tri-O-acetyl-d-glucopyranose in the presence of CdCO3 in boiling toluene; (2) sulfation at C-3 of the resulting 3β-TBDMSi-7β-GlcNAc with sulfur trioxide-trimethylamine complex in pyridine; and (3) direct amidation at C-24 of the 3β-sulfooxy-7β-GlcNAc conjugate with glycine methyl ester hydrochloride (or taurine) using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4- methylmorpholinium chloride as a coupling agent in DMF. The structures of the multi-conjugated bile acids were characterized by liquid chromatography-mass spectrometry with an electrospray ionization probe under the positive and negative ionization modes.
AB - The chemical synthesis of 3β,7β-dihydroxy-5-cholen-24-oic acid, triply conjugated by sulfuric acid at C-3, by N-acetylglucosamine (GlcNAc) at C-7, and by glycine or taurine at C-24, is described. These are unusual, major metabolites of bile acid found to be excreted in the urine of a patient with Niemann-Pick disease type C1. Analogous double-conjugates of 3β-hydroxy-7-oxo-5-cholen-24-oic acid were also prepared. The principal reactions involved were: (1) β-d-N-acetylglucosaminidation at C-7 of methyl 3β-tert-butyldimethylsilyloxy (TBDMSi)-7β-hydroxy-5-cholen-24-oate with 2-acetamido-1α-chloro-1,2-dideoxy-3,4,6-tri-O-acetyl-d-glucopyranose in the presence of CdCO3 in boiling toluene; (2) sulfation at C-3 of the resulting 3β-TBDMSi-7β-GlcNAc with sulfur trioxide-trimethylamine complex in pyridine; and (3) direct amidation at C-24 of the 3β-sulfooxy-7β-GlcNAc conjugate with glycine methyl ester hydrochloride (or taurine) using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4- methylmorpholinium chloride as a coupling agent in DMF. The structures of the multi-conjugated bile acids were characterized by liquid chromatography-mass spectrometry with an electrospray ionization probe under the positive and negative ionization modes.
KW - Electrospray ionization mass spectrometry
KW - Tandem mass spectrometry
KW - Unsaturated bile acid
KW - Unusual bile acid multi-conjugates
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U2 - 10.1016/j.steroids.2005.07.008
DO - 10.1016/j.steroids.2005.07.008
M3 - Article
C2 - 16197972
AN - SCOPUS:28544435981
VL - 71
SP - 18
EP - 29
JO - Steroids
JF - Steroids
SN - 0039-128X
IS - 1
ER -