Potential bile acid metabolites. 14. Hyocholic and muricholic acid stereoisomers.

Iida, Takashi; Momose, Toshiaki; Tamura, Toshitake; Matsumoto, Tarô; Chang, Frederic C.; Goto, Junichi; Nambara, Toshio

doi:10.1016/s0022-2275(20)38283-3

Cited by 41 publications

(10 citation statements)

References 24 publications

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“…7 ␣ ,12 ␣ -Dihydroxy-3 ␣ -diphenylmethoxy-cholanoic acid was synthesized as described (27). The following compounds were synthesized according to published procedures: allocholate (32), norcholate (33), ␣ -muricholate (34), ␤ -muricholate (34), -muricholate (34), hyocholate (34), ursocholate (35), and 7 ␣ ,12 ␣ -dihydroxy-3-oxo-cholanoate (29,36). The taurine conjugates of bile acids were synthesized using the mixed anhydride method (37).…”

Section: Synthesis Of Bile Acid Analoguesmentioning

confidence: 99%

Substrate specificity of the ileal and the hepatic Na+/bile acid cotransporters of the rabbit. I. Transport studies with membrane vesicles and cell lines expressing the cloned transporters

Kramer¹,

Stengelin²,

Baringhaus³

et al. 1999

Journal of Lipid Research

101

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The substrate specificity of the ileal and the hepatic Na ؉ /bile acid cotransporters was determined using brush border membrane vesicles and CHO cell lines permanently expressing the Na ؉ /bile acid cotransporters from rabbit ileum or rabbit liver. The hepatic transporter showed a remarkably broad specificity for interaction with cholephilic compounds in contrast to the ileal system. The anion transport inhibitor diisothiocyanostilbene disulfonate (DIDS) is a strong inhibitor of the hepatic Na ؉ /bile acid cotransporter, but does not show any affinity to its ileal counterpart. Inhibition studies and uptake measurements with about 40 different bile acid analogues differing in the number, position, and stereochemistry of the hydroxyl groups at the steroid nucleus resulted in clear structure-activity relationships for the ileal and hepatic bile acid transporters. The affinity to the ileal and hepatic Na ؉ /bile acid cotransport systems and the uptake rates by cell lines expressing those transporters as well as rabbit ileal brush border membrane vesicles is primarily determined by the substituents on the steroid nucleus. Two hydroxy groups at position 3, 7, or 12 are optimal whereas the presence of three hydroxy groups decreased affinity. Vicinal hydroxy groups at positions 6 and 7 or a shift of the 7-hydroxy group to the 6-position significantly decreased the affinity to the ileal transporter in contrast to the hepatic system. 6-Hydroxylated bile acid derivatives are preferred substrates of the hepatic Na ؉ /bile acid cotransporter. Surprisingly, the 3 ␣ -hydroxy group being present in all natural bile acids is not essential for high affinity interaction with the ileal and the hepatic bile acid transporter. The 3 ␣ -hydroxy group seems to be necessary for optimal transport of a bile acid across the hepatocyte canalicular membrane. A modification of bile acids at the 3-position therefore conserves the bile acid character thus determining the 3-position of bile acids as the ideal position for drug targeting strategies using bile acid transport pathways.

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Section: Synthesis Of Bile Acid Analoguesmentioning

confidence: 99%

Substrate specificity of the ileal and the hepatic Na+/bile acid cotransporters of the rabbit. I. Transport studies with membrane vesicles and cell lines expressing the cloned transporters

Kramer¹,

Stengelin²,

Baringhaus³

et al. 1999

Journal of Lipid Research

101

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“…The biotransformation shown in Scheme 2A was scaled up to 100 mg scale and the product was isolated again by acidification and filtration/extraction (see Experimental and/or Supplementary Materials for details). In this way an efficient and simple access to the rare ω-muricholic acid 6 [13] was optimized.…”

Section: Resultsmentioning

confidence: 99%

Section: Scale-up and Isolation Ofmentioning

confidence: 99%

“…Compound 1 1 H NMR (DMSO-d 6 ), δ: 11.91 (1H, s br, COOH), 4.27 (1H, d, J = 5.0, OH-3), 4.15 (1H, s br, OH-6), 3.84 (1H, d, J = 2.9 Hz, OH-7), 3.60 (1H, dd, J 5,6 = 5.3, J 6,7 = 3.4 Hz, H-6), 3.58 (1H, ddd, J 6,7 = 3.4, J 7,8 = 2.8, J 5,7 = 1.0 Hz, H-7), 3.13 (1H, m, H-3), 0.89 (3H, d, J = 6.5 Hz, CH 3 -21), 0.84 (3H, s, CH 3 -19), 0.61 (3H, s, CH 3 -18); 13 C NMR (DMSO-d 6 ), δ 174.8 (1C, s, COOH), 70.9 (1C, d, C-6), 70.4 (1C, d, C-3), 68.5 (1C, d, C-7), 55.5 (1C, d, 49.9 (1C, d, C-14), 48.0 (1C, d, C-5), 42.0 (1C, s, C-13), 39.3 (1C, t, C-12), 38.2 (1C, d), 35.6 (1C, t, C-1), 35.5 (1C, s, C-10), 34.9 (1C, d, C-20), 32.5 (1C, t), 32.2 (1C, d, C-9), 30.72 (1C, t), 30.66 (1C, t), 30.62(1C, t), 27.7 (1C, t), 23.1 (1C, q, CH 3 -19), 23.0 (1C, t), 20.3 (1C, t), 18.1 (1C, q, CH 3 -21), 11.6 (1C, q, CH 3 -18). ESI-MS: [m + Na] + : 431.2.…”

Section: Characterization Of Commercially Available 1 Andmentioning

confidence: 99%

“…The product was recovered via precipitation by acidification of the reaction mixture and subsequent filtration to afford a white amorphous powder in quantitative yield. 1 H NMR (DMSO-D 6 ), δ: 11.72 (1H, s br, COOH), 4.42 (1H, s br, OH), 4.27 (1H, s br, OH), 3.88 (1H, d, J = 5.4 Hz, OH-7), 3.50 (1H, dd, J 6,7 = 9.4, J 5,6 = 5.5 Hz, H-6), 3.25 (1H, m, H-3), 3.07 (1H, t, J 6,7 = J 7,8 = 9.4 Hz, H-7), 0.88 (3H, d, J = 6.5 Hz, CH 3 -21), 0.86 (3H, s, CH 3 -19), 0.61 (3H, s, CH 3 -18); 13 C NMR (DMSO-D 6 ), δ: 174.5 (1C, s, COOH, 74.5 (1C, d, C-7), 72.2 (1C, d, C-6), 70.2 (1C, d, C-3), 56.1 (1C, d), 54.9 (1C, d), 48.1 (1C, d), 43.5 (1C, s), 41.5 (1C, d), 40.0 (1C, t), 39.3 (1C, d), 35.4 (1C, t), 35.06 (1C, s), 35.04 (1C, d), 31.0 (2 C, t), 30.6 (1C, t), 30.3(1C, t), 28.3 (1C, t), 26.7 (1C, t), 23.7 (1C, q, CH 3 -19), 21.2 (1C, t), 18.5 (1C, q, CH 3 -21), 12.3 (1C, q, CH 3 -18). ESI-MS: [m + Na] + : 431.2.…”

Section: Scale-up and Isolation Ofmentioning

confidence: 99%

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Synthesis of ω‐Muricholic Acid by One‐Pot Enzymatic Mitsunobu Inversion using Hydroxysteroid Dehydrogenases

et al. 2021

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The biocatalyzed conversion of hyocholic acid (3α,6α,7αtrihydroxy-5β-cholan-24-oic acid) into ω-muricholic acid (3α,6α,7β-trihydroxy-5β-cholan-24-oic acid) has been obtained exploiting a small library of 7α-and 7β-HSDHs (hydroxysteroid dehydrogenases). The process has been optimized and per-formed avoiding the isolation of the 7-oxo intermediate using the appropriate coupled enzymes for the in situ cofactor regeneration. Moreover, the biocatalyzed reduction of 6,7dioxolithocholic acid (3α-hydroxy-6,7-dioxo-5β-cholan-24-oic acid) was also investigated.

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Carbon‐13 NMR spectra of bile acid derivatives. Part III. Unsaturated 5β‐cholanoic acids

Iida

Goto

Nambara

1993

Magnetic Reson in Chemistry

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Potential bile acid metabolites. 14. Hyocholic and muricholic acid stereoisomers.

Cited by 41 publications

References 24 publications

Substrate specificity of the ileal and the hepatic Na+/bile acid cotransporters of the rabbit. I. Transport studies with membrane vesicles and cell lines expressing the cloned transporters

Substrate specificity of the ileal and the hepatic Na+/bile acid cotransporters of the rabbit. I. Transport studies with membrane vesicles and cell lines expressing the cloned transporters

Synthesis of ω‐Muricholic Acid by One‐Pot Enzymatic Mitsunobu Inversion using Hydroxysteroid Dehydrogenases

Carbon‐13 NMR spectra of bile acid derivatives. Part III. Unsaturated 5β‐cholanoic acids

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