- New cyclic dimers of cholic acid
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Two new cyclic dimers of cholic acid were obtained in the reaction of 3-O-acetyl methyl cholate with oxalyl chloride. The oxalates bound the cholate subunits "side-to-side" as a result of acylation of 7α and 12α OH groups in the substrate. The selective deprotection of hydroxy groups at C-3 and C-24 proved to be rather difficult and led to various products depending on the reaction conditions. Springer-Verlag 2005.
- Lotowski, Zenon,Guzmanski, Dariusz
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- The 'triamino-analogue' of methyl cholate; a practical, large-scale synthesis
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The triamino steroids 2 are in demand as facial amphiphiles and starting materials for supramolecular chemistry. 2 (R = Me)is now available from cholic acid 1 in substantial quantities via a new, high-yielding procedure.
- Davis, Anthony P.,Pérez-Payán, M. Nieves
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- Mimicking Enzymes: Asymmetric Induction inside a Carbamate-Based Steroidal Cleft
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Cholic acid has been elaborated into a carbamate-based tripodal architecture, which is able to promote an asymmetric organic transformation inside its chiral cavity. The nature of this steroidal catalyst has been disclosed by quantum-chemical calculations. It comprises the preorganization and confinement of the reagents within the cavity of the steroid to form a supramolecular complex held together by means of cooperative H-bond contacts. This operational mode resembles that of some enzymes.
- Concellón, Carmen,Martín, Judith,Gallegos, Miguel,Fanjul-Mosteirín, Noé,Costales, Aurora,Pendás, ángel Martín,Del Amo, Vicente
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supporting information
p. 3994 - 3997
(2019/06/17)
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- Novel liver-specific nitric oxide (NO) releasing drugs with bile acid as both NO carrier and targeting ligand
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Novel liver-specific nitric oxide (NO) releasing drugs with bile acid as both the NO carrier and targeting ligand were designed and synthesized by direct nitration of the hydroxyl group in bile acids or the 3-O-hydroxyl alkyl derivatives, with the intact 24-COOH being preserved for hepatocyte specific recognition. Preliminary biological evaluation revealed that oral administrated targeted conjugates could protect mice against acute liver damage induced by acetaminophen or carbon tetrachloride. The nitrate level in the liver significantly increased after oral administration of 1e while nitrate level in the blood did not significantly change. Co-administration of ursodeoxycholic acid (UDCA) significantly antagonized the increase of nitrate in the liver resulted by administration of 1e.
- Jin, Xue-Yuan,Fan, Shi-Yong,Li, Hong-Wu,Shi, Wei-Guo,Chen, Wei,Wang, Hui-Fen,Zhong, Bo-Hua
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p. 787 - 790
(2014/06/09)
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- Differentially-protected steroidal triamines; scaffolds with potential for medicinal, supramolecular, and combinatorial chemistry
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Cholic acid 2a has been converted into two new orthogonally-protected triamino scaffolds, 13 and 14. The synthesis proceeds via the bis-Boc-NH-substituted azide 10, for which an improved preparation is described. After removal of the Boc groups, the two a
- Amo, Vicente Del,Siracusa, Laura,Markidis, Theodoros,Baragana, Beatriz,Bhattarai, Khadga M.,Galobardes, Marta,Naredo, Gregorio,Perez-Payan, M. Nieves,Davis, Anthony P.
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p. 3320 - 3328
(2007/10/03)
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- Liver-selective glucocorticoid antagonists: A novel treatment for type 2 diabetes
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Hepatic blockade of glucocorticoid receptors (GR) suppresses glucose production and thus decreases circulating glucose levels, but systemic glucocorticoid antagonism can produce adrenal insufficiency and other undesirable side effects. These hepatic and systemic responses might be dissected, leading to liver-selective pharmacology, when a GR antagonist is linked to a bile acid in an appropriate manner. Bile acid conjugation can be accomplished with a minimal loss of binding affinity for GR. The resultant conjugates remain potent in cell-based functional assays. A novel in vivo assay has been developed to simultaneously evaluate both hepatic and systemic GR blockade; this assay has been used to optimize the nature and site of the linker functionality, as well as the choice of the GR antagonist and the bile acid. This optimization led to the identification of A-348441, which reduces glucose levels and improves lipid profiles in an animal model of diabetes.
- Von Geldern, Thomas W.,Tu, Noah,Kym, Philip R.,Link, James T.,Jae, Hwan-Soo,Lai, Chunqiu,Apelqvist, Theresa,Rhonnstad, Patrik,Hagberg, Lars,Koehler, Konrad,Grynfarb, Marlena,Goos-Nilsson, Annika,Sandberg, Johnny,Osterlund, Marie,Barkhem, Tomas,H?glund, Marie,Wang, Jiahong,Fung, Steven,Wilcox, Denise,Nguyen, Phong,Jakob, Clarissa,Hutchins, Charles,F?rnegf?rdh, Mathias,Kauppi, Bj?rn,?hman, Lars,Jacobson, Peer B.
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p. 4213 - 4230
(2007/10/03)
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- Regioselective esterification of polyhydroxylated steroids by Candida antarctica lipase B
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The regioselectivity of Candida antarctica lipase B towards the acetylation of polyhydroxylated steroids has been systematically investigated. The enzyme showed a marked preference for the alcoholic moieties on the A ring and: on the steroidal side chain, making it possible the selective acylation at the positions 3 or 21 of polyhydroxy steroids. Acylation with the synthetically useful esters chloroacetate and levulinate was also accomplished, whereas esterification with benzoate and pivaloate was unsuccessful.
- Bertinotti, Anna,Carrea, Giacomo,Ottolina, Gianluca,Riva, Sergio
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p. 13165 - 13172
(2007/10/02)
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- Substituted Methyl 5β-Cholan-24-oates. I - 17O NMR Spectral Characterization
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Methyl esters of four common bile acids, 3α-hydroxy-5β-cholan-24-oic (lithocholic) acid, 3α,7α-dihydroxy-5β-cholan-24-oic (chenodeoxycholic) acid, 3α,12α-dihydroxy-5β-cholan-24-oic (deoxycholic) acid and 3α,7α,12α-trihydroxy-5β-cholan-24-oic (cholic) acid, and 14 acetylated, trifluoroacetylated, mesylated and oxo derivatives of methyl 5β-cholan-24-oates were prepared and their 17O NMR spectra recorded.In spite of their relatively high molecular masses and the rigid molecular structure of the steroid skeleton, most of the oxygens included in these structures gave well resolved 17O NMR resonance lines at natural abundance in 0.25-0.5 M acetonitrile solutions at 75 deg C.In agreement with the present 17O NMR results, molecular mechanics calculations revealed that a hydroxy substituent located at the 3α-position clearly differs from the hydroxyls at the 7α- and 12α-positions.This is due to the fact that the 3α-hydroxyl possesing only two γ-carbons at antiperiplanar positions is less shielded than the other hydroxyls influenced also by the shielding effects of γ-gauche carbons.The spectral deconvolution of the overlapping signals of the 7α- and 12α-hydroxyls is based on a computer-aided method or on chemical substitutions.The oxo groups located at the longitudinal (3-oxo) vs. transversal (7- and 12-oxo) axes of the steroid framework show very different quadrupolar relaxation properties and 17O NMR linewidths owing to the strong anisotropy of overall molecular motion.In contrast, the 17O NMR linewidths of all 3α-, 7α- and 12α-hydroxyls are very similar and clearly smaller than those of the corresponding oxo groups, revealing that their quadrupolar relaxtion is merely determined by their internal rotation rather than by the overall molecular motion. - Keywords: NMR 17O NMR 17O chemical shifts 17O relaxation Methyl 5β-cholan-24-oates Methyl esters of bile acids
- Kolehmainen, Erkki,Kaartinen, Mari,Kauppinen, Reijo,Kotoneva, Jari,Lappalainen, Kari,et al.
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p. 441 - 445
(2007/10/02)
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