- Coordination of sodium cation to an oxygen function and olefinic double bond to form molecular adduct ion in fast atom bombardment mass spectrometry
-
Steroidal allylic alcohols formed Na+ adduct ion peaks [M+Na]+ by the addition of NaCl in FAB mass spectrometry. A comparison of the intensities of the adduct ion peaks of allylic alcohols with those of the corresponding saturated alcohols and olefin suggested that the olefinic double bond and the proximal hydroxyl group had coordinated to Na +. The adduct ion was stable and did not undergo dehydroxylation. We suggest that the Na+ adduct ion will be useful for the molecular weight determination of allylic alcohols which are susceptible to dehydroxylation under FAB mass spectrometric conditions. Na+ adduct ions of α, β-unsaturated carbonyl compounds were also investigated.
- Morisaki, Naoko,Kobayashi, Hisayoshi,Yamamura, Yumiko,Morisaki, Masuo,Nagasawa, Kazuo,Hashimoto, Yuichi
-
-
Read Online
- Synthesis of 24-functionalized oxysterols
-
The syntheses of (24S)-24,25-epoxycholesterol, (24S)-hydroxycholesterol, and 24-ketocholesterol are described. The compounds belong to oxysterols, which can be considered to be the modulators of cholesterol metabolism. The asymmetric hydroxylation of desmosterol acetate according to Sharpless was used as the key reaction in the stereoselective introduction of functionality in position 24.
- Khripach,Zhabinskii,Konstantinova,Khripach,Antonchick
-
-
Read Online
- Elucidation of Distinct Modular Assemblies of Smoothened Receptor by Bitopic Ligand Measurement
-
Class F G protein-coupled receptors are characterized by a large extracellular domain (ECD) in addition to the common transmembrane domain (TMD) with seven α-helixes. For smoothened receptor (SMO), structural studies revealed dissected ECD and TMD, and th
- Zhao, Fei,Wu, Yiran,Zhou, Fang,Xue, Dongxiang,Zhao, Simeng,Lu, Wanglong,Liu, Xiaoyan,Hu, Tao,Qiu, Yanli,Li, Rongyan,Gu, Tangjie,Xu, Yueming,Xu, Fei,Zhong, Guisheng,Jiang, Zhongxing,Zhao, Suwen,Tao, Houchao
-
supporting information
p. 13830 - 13840
(2021/09/28)
-
- Synthesis method of saringosterol
-
The invention discloses a synthesis method of saringosterol. The synthesis method comprises the following steps of: carrying out esterification on hyodeoxycholic acid serving as a raw material to generate hyodeoxycholate or directly carrying out sulfonylation reaction on the hyodeoxycholate serving as a raw material to generate 3, 6-disulfonyl hyodeoxycholate, then carrying out nucleophilic substitution-elimination reaction to generate 3beta-hydroxychol-5-ene-24-acid ester, then performing reaction with N, O-dimethyl hydroxylamine to prepare weinreb amide, and carrying out two-step Green Nisi reaction to finally obtain sargassterol. The synthesis method disclosed by the invention is mild in reaction condition, relatively short in reaction time, low in price of the starting raw material hyodeoxycholic acid and the reaction reagent, relatively high in final yield and suitable for large-scale preparation of the sargassterol.
- -
-
-
- An effective synthesis of ursodeoxycholic acid from dehydroepiandrosterone
-
A novel synthetic route of producing ursodeoxycholic acid (UDCA) was developed through multiple reactions from plant-source dehydroepiandrosterone (DHEA), with a Mistunobu reaction and regioselective allyl oxidationat as the key steps. The reaction conditions of the key allyl oxidation reaction were also investigated and optimized, including solvent, oxidant and reaction temperature. In this novel route for the preparation of UDCA, most of the reaction steps have high conversions and overall yield up to 35% for 8 steps. Since all starting materials are cost-effective, commercially available and effectively avoided the risk of animal derived raw materials, this promising synthetic route offers economical and efficient strategies for potential production of UDCA.
- Chen, Wang,Hu, Daihua,Feng, Zili,Liu, Zhaopeng
-
supporting information
(2021/06/16)
-
- A concise synthesis of 25-Hydroxycholesterol from hyodesoxycholic Acid
-
A simple, efficient and economical method has been developed for the synthesis of 25-hydroxycholesterol in seven steps from hyodesoxycholic acid with an overall yield of 39%. The preparation of the 3β-tetrahydropyranyloxychol-5-en-24-al from 3β-tetrahydropyranyloxychol-5-en-24-oic acid methyl ester with di-isobutylaluminium hydride was achieved instead of using the conventional two-step reaction, thus avoiding the use of the toxic oxidant CrO3. The terminal product was obtained by hydroxybromination of desmosterol with N-bromosuccinimide/H2O, followed by reduction and deprotection of the halohydrins with LiAlH4. This simplified route gave an increased overall yield and used economical and environmentally benign reagents.
- Jin, Can,Wang, Yulei,Sun, Bin,Su, Weike
-
-
- OXYSTEROLS AND METHODS OF USE THEREOF
-
Compounds are provided according to Formula (I): and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein R2, R3, R4, R5, and and R6 are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of conditions.
- -
-
Paragraph 00750
(2018/05/16)
-
- Cholesterol molecular probe as well as preparation method and application thereof
-
The invention discloses a cholesterol molecular probe and a preparation method thereof. The cholesterol molecular probe shown as a formula (I) is prepared by taking lithocholic acid as a raw material through esterification reaction, oxidization reaction, dehydrogenation reaction, carbonyl protection reaction, reduction reaction, hydroxyl protection reaction, reduction reaction, iodination reaction, substitution reaction and de-protection reaction. The invention further discloses application of the cholesterol molecular probe shown as the formula (I) to identification of cholesterol modified protein. The cholesterol molecular probe provided by the invention can be used for simulating normal cholesterol to promote cell growth, and prompting the shearing ripening of the cholesterol modified protein hedgehog, and can also be used for researching cholesterol modification of the protein.
- -
-
-
- Novel 3,4-seco bile acid diamides as selective anticancer proliferation and migration agents
-
A series of new seco-A ring bile acid diamides were synthesized, and their antiproliferative activities against PC3M (prostate), HT29 (colon) and ES-2 (ovarian) cancer cell lines were investigated using SRB assays. Most synthesized compounds presented improved antiproliferative activities compared to the parent bile acids (IC50> 80 μM), especially the piperazine conjugated compound 27 with IC50values of 1.07, 4.58 and 3.86 μM against PC3M, HT29 and ES-2 cancer cell lines, respectively. In addition, all the tested compounds showed less cytotoxic activity on a noncancerous cell line (HAF), and the most active compound 27 exhibited the highest selectivity (Selectivity Index, SIPC3M= 26.3). Furthermore, 27 could also enhance G1 arrest in PC3M cell, revealed by cell cycle analysis, and increase anti-migration activity on PC3M cells, confirmed by transwell migration assay.
- Mao, Shi-Wei,Chen, Huang,Yu, Li-Fang,Lv, Fang,Xing, Ya-Jing,Liu, Ting,Xie, Jia,Tang, Jie,Yi, Zhengfang,Yang, Fan
-
p. 574 - 583
(2016/07/22)
-
- Design and synthesis of a crosslinker for studying intracellular steroid trafficking pathways
-
A crosslinker was designed and synthesized as a molecular tool for potential use in probing the intracellular trafficking pathways of steroids. The design was guided by computational modeling based upon a model for the transfer of cholesterol between two
- Byrd, Katherine M.,Arieno, Marcus D.,Kennelly, Megan E.,Estiu, Guillermina,Wiest, Olaf,Helquist, Paul
-
p. 3843 - 3851
(2015/07/27)
-
- OXYSTEROLS AND METHODS OF USE THEREOF
-
Compounds are provided according to Formula (I) and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein X, Y, R1, R2a, R2b, R4a, R4b, R5a, R5b/
- -
-
-
- NEUROACTIVE STEROIDS AND METHODS OF USE THEREOF
-
3beta, 17beta disubstituted steroidal compounds, pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, are provided for the prevention and treatment of a variety of CNS-related conditions.
- -
-
Paragraph 00277
(2014/10/15)
-
- Structure-activity relationships of oxysterol-derived pharmacological chaperones for Niemann-Pick type C1 protein
-
Niemann-Pick disease type C is a fatal neurodegenerative disease, and its major cause is mutations in NPC1 gene. This gene encodes NPC1 protein, a late endosomal polytopic membrane protein required for intracellular cholesterol trafficking. One prevalent mutation (I1061T) has been shown to cause a folding defect, which results in failure of endosomal localization of the protein, leading to loss-of-function phenotype. We have previously demonstrated that several oxysterols and their derivatives act as pharmacological chaperones; binding of these compounds to NPC1I1061T mutant protein corrects the localization/maturation defect of the mutant protein. Here, we disclose detailed structure-activity relationships of oxysterol derivatives as pharmacological chaperones for NPC1I1061T mutant.
- Ohgane, Kenji,Karaki, Fumika,Noguchi-Yachide, Tomomi,Dodo, Kosuke,Hashimoto, Yuichi
-
supporting information
p. 3480 - 3485
(2014/07/22)
-
- Total synthesis and pharmacological characterization of solomonsterol A, a potent marine pregnane-X-receptor agonist endowed with anti-inflammatory activity
-
Recently, we reported the identification of a novel class of pregnane-X-receptor (PXR) agonists, solomonsterols A and B, isolated from the marine sponge Theonella swinhoei. Preliminary pharmacological studies demonstrated that these natural compounds are potential leads for the treatment of human disorders characterized by dysregulation of innate immunity. In this article, we describe the first total synthesis of solomonsterol A and its in vivo characterization in animal models of colitis. Using transgenic mice expressing the human PXR, we found that administration of synthetic solomonsterol A effectively protects against development of clinical signs and symptoms of colitis and reduced the generation of TNFα, a signature cytokine for this disorder. In addition, we have provided the first evidence that solomonsterol A might act by triggering the expression of TGFβ and IL-10, potent counter-regulatory cytokines in inflammatory bowel diseases (IBD). Finally, we have shown that solomonsterol A inhibits NF-κB activation by a PXR dependent mechanism. In summary, solomonsterol A is a marine PXR agonist that holds promise in the treatment of inflammation-driven immune dysfunction in clinical settings.
- Sepe, Valentina,Ummarino, Raffaella,D Auria, Maria Valeria,Mencarelli, Andrea,D Amore, Claudio,Renga, Barbara,Zampella, Angela,Fiorucci, Stefano
-
scheme or table
p. 4590 - 4599
(2011/09/14)
-
- Chemical synthesis of the 3-sulfooxy-7-N-acetylglucosaminyl-24-amidated conjugates of 3β,7β-dihydroxy-5-cholen-24-oic acid, and related compounds: Unusual, major metabolites of bile acid in a patient with Niemann-Pick disease type C1
-
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
- Iida, Takashi,Kakiyama, Genta,Hibiya, Yohei,Miyata, Shohei,Inoue, Takehiko,Ohno, Kohsaku,Goto, Takaaki,Mano, Nariyasu,Goto, Junichi,Nambara, Toshio,Hofmann, Alan F.
-
-
- Production method of steroid compound
-
An object of the present invention is to provide a novel method for producing a steroid compound. The present invention provides a method for producing 3,7-dioxo-5β-cholanic acid or ester derivatives thereof, which uses, as raw materials, sterols having d
- -
-
Page/Page column 61
(2008/06/13)
-
- Efficient, stereoselective synthesis of 24(s), 25-epoxycholesterol
-
Efficient, stereoselective syntheses of 24(S), 25-epoxycholesterol (1) have been developed starting from cholenic acid (4) or stigmasterol (8), both featuring as the key step Sharpless asymmetric dihydroxylation of desmosterol acetate (2). This work permits preparation of gram quantities of 1 for further evaluation as a natural regulator of cholesterol metabolism, specifically, e.g., as a ligand for the LXRα. nuclear receptor.
- Tomkinson, Nicholas C. O.,Willson, Timothy M.,Russel, Jonathon S.,Spencer, Thomas A.
-
p. 9919 - 9923
(2007/10/03)
-
- The synthesis of branched steroidal prodrugs of nitrogen mustard for antitumor targeting via reconstituted LDL
-
Bis and tris nitrogen mustard oleoyl-steroid carbamates were synthesized from commercially available cholenic acids for antitumor drug targeting via the LDL pathway. The tris-mustards were prepared through triester intermediates made from selective alkylation of the dianion of t-butyl 3-(diethyl malonyl)-propionate 10 with steroid iodides 8.
- Dubowchik, Gene M.,Firestone, Raymond A.
-
p. 4523 - 4526
(2007/10/02)
-
- Synthesis and Stereochemistry of Ficisterol and Norficisterol: Biosynthetic Implications
-
All four possible C-23 and C-24 stereoisomers of ficisterol and norficisterol were synthesized via Ireland's ester enolate Claisen rearrangement.The stereochemistry of each isomer was determined by a combination of stereochemical deductions derived from the Claisen mechanism, and chemical correlations with known standards.The resulting stereostructures (1a) and (2a) are consistent with the hypothesis that dihydrocalysterol (3) and (23R,24R)-methylenecholesterol (42) are the respective biosynthetic precursors of ficisterol and norficisterol, thus supporting a novel mechanism for 27-norergostane biosynthesis.In the course of the stereochemically significant synthesis, 23,24-dimethyl-22-dehydrocholesterol (37) - the presumed biosynthetic precursor of gorgosterol (41) - was prepared by a route that lends itself readily to the synthesis of isotopically labelled analogues.
- Shu, Arthur Y. L.,Djerassi, Carl
-
p. 1291 - 1306
(2007/10/02)
-
- A convenient synthesis of 3β,12α-, 3β,7α-, and 3β,7β-dihydroxy-5-cholen-24-oic acids: Unusual bile acids in human biological fluids
-
The unusual bile acids 3β,12α- (V), 3β,7α- (XIIIa), and 3β,7β- (XIIIb) dihydroxy-5-cholen-24-oic acids were synthesized conveniently from the 3-oxo derivatives of deoxycholic (I) and lithocholic (VI) acids, respectively, to provide authentic samples for the gas chromatography-mass spectrometric determination of these bile acids in the abnormal metabolism of bile acids.
- Tohma,Mahara,Takeshita,Kurosawa
-
p. 331 - 338
(2007/10/02)
-
- SYNTHETIC STUDIES ON VITAMIN D ANALOGUES VI. A NEW SYNTHESIS OF 25-HYDROXYCHOLESTEROL FROM LITHOCHOLIC ACID
-
The conversion of lithocholic acid (1) into 25-hydroxycholesterol (10) via methyl 3β-hydroxy-5-cholenate (6) is described.
- Miyamoto, Katsuhito,Kubodera, Noboru,Murayama, Eigoro,Ochi, Kiyoshige,Mori, Takashi,Matsunaga, Isao
-
p. 513 - 522
(2007/10/02)
-
- Selective Delivery of Cytotoxic Compounds to Cells by the LDL Pathway
-
Cancer cells need cholesterol to make new membrane.They get it either by de novo synthesis or low-density lipoprotein (LDL), or both.Some types of cancer have very high LDL requirements.LDL particles, which circulate in the blood, contain a cholesteryl ester core surrounded by a phospholipid coat containing apoproteins that are recognized by LDL receptors on cell surfaces.After attachment to cells, LDL is endocytosed into lysosomes, where the core is exposed and hydrolyzed.A technique is known whereby LDL can be isolated, its core removed and replaced by a compatible lipophilic substance, and then reconstituted into intact LDL particles that are recognized and internalized by cells in the normal manner.A series of cytotoxic compounds has been synthesized, designed to be compatible with reconstituted LDL, and directed against cancers that copiously internalize LDL.They were evaluated by measuring the toxicity of reconstituted LDL toward test cells bearing LDL receptors.Selectivity was determined by comparison, either with mutant cells with few LDL receptors or with reconstituted methylated LDL (which is not recognized by LDL receptors) on normal cells.Two compounds, 19 and 25, were found that reconstitute well, kill or arrest the test cells at reasonably low concentrations, and are completely selective, suggesting that they are delivered to cells exclusively via the LDL pathway.
- Firestone, Raymond A.,Pisano, Judith M.,Falck, J. R.,McPhaul, Michael M.,Krieger, Monty
-
p. 1037 - 1043
(2007/10/02)
-
- Process for preparing 25-hydroxycholesterol
-
The synthesis of 25-hydroxycholesterol and 25-hydroxycholecalciferol from animal bile starting materials in which hyodeoxycholic acid or an ester thereof is converted to the 3β-hydroxy-5-cholenic acid alkyl ester, and this is converted to 3β-hydroxy-25-cyano-5-cholene by a series of steps by which the sterol nucleus is stabilized by placing a protecting group at the 3 position and then extending the chain from the carbon at the 24 position to a cyanide group at the 25 position. The compound so formed is subjected to a series of reactions by which it is transformed into 25-hydroxy-7-dehydrocholesterol which may then be irradiated with ultraviolet light to 25-hydroxycholecalciferol. The invention discloses new and improved processes for preparing these end products and also new compounds formed as intermediates and processes for preparing these intermediates.
- -
-
-