- Synthesis of (20S)-[7,7,21,21-2H4]-3β-(tert- butyldimethylsilanyloxy)-20-methyl-pregn-5-en-21-ol, a useful intermediate for the preparation of deuterated isotopomers of sterols
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(20S)-[7,7,21,21-2H4]-3β-(tert- Butyldimethylsilanyloxy)-20-methyl-pregn-5-en-21-ol, an intermediate for the preparation of deuterated isotopomers of sterols to be used as standards for biomedical studies, was prepared by reduction with dichloroaluminum deuteride of ethyl (20S)-3β-(tert-butyldimethylsilanyloxy)-7-oxo-pregn-5-en-20-carboxylate. Using controlled experimental conditions, it has also been shown that the dichloroaluminum hydride reduction of a 7-keto steroid affords the corresponding 7β-hydroxy derivative in a highly stereoselective manner.
- Ciuffreda, Pierangela,Casati, Silvana,Bollini, Deborah,Santaniello, Enzo
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- Structure-activity relationship studies of Niemann-Pick type C1-like 1 (NPC1L1) ligands identified by screening assay monitoring pharmacological chaperone effect
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A number of hereditary diseases are caused by defective protein trafficking due to a folding defect resulting from point mutations in proteins. Ligands that bind to the folding intermediates of such mutant proteins and rescue their trafficking defects, known as pharmacological chaperones, have promise for the treatment of certain genetic diseases, including Fabry disease, cystic fibrosis, and Niemann-Pick disease type C. Here we show that this pharmacological chaperone effect can be used for ligand screening, that is, binding of candidate ligands can be detected by monitoring the ligand-mediated correction of a localization defect caused by artificially introduced point mutations of the protein of interest. Using this method, we discovered novel steroidal ligands of Niemann-Pick type C1-like 1 (NPC1L1), an intestinal cholesterol transporter that is the target of the cholesterol absorption inhibitor ezetimibe, and conducted structure-activity relationship studies. We also present data indicating that the binding site of the new ligands is distinct from both the N-terminal sterol-binding domain and the ezetimibe-binding site.
- Karaki, Fumika,Ohgane, Kenji,Dodo, Kosuke,Hashimoto, Yuichi
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- Chemical synthesis of 7α-hydroxycholest-4-en-3-one, a biomarker for irritable bowel syndrome and bile acid malabsorption
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7α-Hydroxy-cholest-4-en-3-one is a biomarker for bile acid loss, irritable bowel syndrome, and other diseases associated with defective bile acid biosynthesis. Furthermore, 7α-hydroxy-cholest-4-en-3-one is the physiological substrate for cytochrome P450 8B1 (P450 8B1 or CYP8B1), the oxysterol 12α-hydroxylase enzyme implicated in obesity and cardiovascular health. We report the chemical synthesis of this physiologically important oxysterol beginning with cholesterol. The key feature of this synthesis involves a regioselective C3-allylic oxidation of a 3-desoxy-Δ4-7α-formate steroid precursor to form 7α-formyloxy-cholest-4-en-3-one, which was saponified to yield 7α-hydroxy-cholest-4-en-3-one.
- Offei, Samuel D.,Arman, Hadi D.,Yoshimoto, Francis K.
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supporting information
(2019/07/31)
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- HEXADECAHYDRO-1H-CYCLOPENTA[A]PHENANTHRENE DERIVATIVES USEFUL IN TREATING PAIN AND INFLAMMATION
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wherein,R1, R2, R3, R4a, R4b and R5 are described herein, or a stereoisomer, enantiomer or tautomer thereof or mixtures thereof, or a pharmaceutically acceptable salt or solvate thereof, are described herein, as well as other compounds. These compounds are useful in treating inflammation and/or pain. Compositions comprising a compound of the invention are also disclosed, as are methods of using the compounds to treat inflammation and/or pain.
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Page/Page column 40; 73-74
(2019/10/29)
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- INDENE DERIVATIVES USEFUL IN TREATING PAIN AND INFLAMMATION
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Compounds of formula (I) wherein, R1, R2, R3, R4a, R4b and R5 are described herein, or a stereoisomer, enantiomer or tautomer thereof or mixtures thereof, or a pharmaceutically acceptable salt or solv
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Page/Page column 60-61; 135-136; 141; 142
(2019/10/29)
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- A new reagent system for efficient silylation of alcohols: Silyl chloride-N-methylimidazole-iodine
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It was found that reactions of alcohols with silyl chlorides in the presence of N-methylimidazole were significantly accelerated by the added iodine, and on this basis a general, and high yielding method for efficient silylation of primary, secondary, and
- Bartoszewicz, Agnieszka,Kalek, Marcin,Nilsson, Johan,Hiresova, Renata,Stawinski, Jacek
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- Iodine-promoted silylation of alcohols with silyl chlorides. Synthetic and mechanistic studies
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An efficient silylating system for 1°, 2°, and 3° alcohols, consisting of a silyl chloride/N-methylimidazole/iodine, was developed. Synthetic and mechanistic aspects of this new reagent system, and particularly the role of iodine were investigated in detail using 1H NMR spectroscopy.
- Bartoszewicz, Agnieszka,Kalek, Marcin,Stawinski, Jacek
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p. 8843 - 8850
(2008/12/21)
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- A Convenient Method for Protection and Deprotection of Alcohols and Phenols as Alkylsilyl Ethers Catalyzed by Iodine under Microwave Irradiation
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Irradiation of alcohols or phenols with tert-butyldimethylsilyl chloride (TBDMSCl) or trimethylsilyl chloride (TMSCl) in presence of catalytic amount (20 mol%) of iodine in a microwave oven for 2 min gives the corresponding silyl ethers in excellent yield. Iodine in methanol deprotects the silyl ether into its parent alcohol or phenol under similar reaction conditions.
- Saxena, Ira,Deka, Nabajyoti,Sarma, Jadab C.,Tsuboi, Sadao
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p. 4185 - 4191
(2007/10/03)
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- Preparation of formate esters from O-TBDMS/O-TES protected alcohols. A one-step conversion using the Vilsmeier-Haack complex POCl3/DMF
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O-tert-Butyldimethylsilylated (O-TBDMS) or O-triethylsilylated (O-TES) alcohols were converted in one step to their corresponding formates under Vilsmeier-Haack conditions (POCl3/DMF). The scope and limitations of this novel reaction for interconverting alcohol protecting groups are described.
- Koeller, Sylvain,Lellouche, Jean-Paul
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p. 7043 - 7046
(2007/10/03)
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- Efficient and chemoselective protection of alcohols and phenols with tert-butyldimethylchlorosilane (TBDMCS) under solvent-free conditions
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Various types of primary and secondary alcohols and phenols can be converted efficiently to their corresponding TBDMS ethers using TBDMCS/imidazole under solvent-free conditions. Elimination of DMF, accompanied with an easy non-aqueous work-up and a high rate enhancement of the reaction are worthy to be mentioned for the presented method. The reactions show absolute chemoselectivity for the protection of primary in the presence of secondary alcohols.
- Firouzabadi, Habib,Etemadi, Shahrad,Karimi, Babak,Jarrahpour, Ali Asghar
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- Extensively deuterated sterols
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Pt-catalyzed H-D exchange of cholestane-3,6-dione under strictly defined conditions gives, after proper functional change, cholesterol that is labelled at positions 1 (partially), 2, 3, 4, 6, 7 (α, partially), and 23 to 27. deuteration / cholesterol / Adams' catalyst
- Starck, Jean-Philippe,Milon, Alain,Nakatani, Yoichi,Ourisson, Guy
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p. 210 - 216
(2007/10/02)
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- The Trifluoromethanesulfonates of Dimethylsilyl Ethers as Intermediates for Silicon Protective Groups
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The reaction of mesityldimethylsilyl ethers with CF3SO3H yields selectively mesitylene.The resulting Si-trifluormethanesulfonates were reacted with t-BuLi to give the corresponding t-BuMe2Si-ethers.Keywords: Alcohol protective groups; t-Butyldimethylsilyl ethers; Mesityldimethylsilyl ethers; Trifluormethanesulfonates.
- Weinzierl, Uwe,Seidel, Wolfgang
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p. 369 - 372
(2007/10/02)
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- Investigation on Mesityldimethylhalosilanes as Protective Reagents for Alcohols
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The use of mesityldimethylhalosilanes as protecting reagents for steroid alcohols was investigated.The resistance of the obtained silyl ethers was tested in various media.The reaction pathway of the acidic hydrolyses of the silyl ethers is explained.
- Weinzierl, Uwe,Seidel, Wolfgang
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p. 917 - 922
(2007/10/02)
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- SPECIFIC ALLYLIC-ALLYLIC COUPLING PROCEDURES EFFECTED BY LIGAND-INDUCED ELIMINATION FROM DI(ALLYLIC)PALLADIUM SPECIES
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Bis(allylic)palladium complexes can be induced to undergo reductive elimination by replacement of phosphine ligands in the system with ?-acidic ligands.The product 1,5-dienes, formed in high yield, are predominantly the 'head-to-head' coupled isomers.The bis(allylic)palladium intermediates may be formed by addition of an allylic Grignard or trialkyl(allylic)tin reagent to an(η3-allyl)palladium chloride complex, or by 1,3-diene condensation.The latter process leads to cyclodimerization, 'unusual' for palladium catalysed reactions.
- Goliaszewski, Alan,Schwartz, Jeffrey
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p. 5779 - 5790
(2007/10/02)
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- Silyl Halides from (Phenylseleno)silanes. Reaction with Oxiranes and Alcohols To Give Hydrolytically Stable Silyl Ethers.
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The preparation of (phenylseleno)silanes and their reactions with halogens (Cl2, Br2, I2) to give silyl halides and diphenyl diselenide are described.Highly hindered tert-butyldimethyl and tert-butyl diphenylsilyl halides were easily prepared.The reaction of silyl bromides and iodides with oxiranes followed by diazabicyclononane treatment gave allylic alcohol silyl ethers.Tertiary alcohols reacted rapidly with silyliodides to give hydrolytically stable silyl ethers.Treatment of the silyl ethers with tetra-n-butylammonium fluoride gave the free alcohols withoutrearrangement or isomerization.
- Detty, Michael R.,Seidler, Mark D.
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p. 1283 - 1292
(2007/10/02)
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