- Asymmetric Catalysis via Cyclic, Aliphatic Oxocarbenium Ions
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A direct enantioselective synthesis of substituted oxygen heterocycles from lactol acetates and enolsilanes has been realized using a highly reactive and confined imidodiphosphorimidate (IDPi) catalyst. Various chiral oxygen heterocycles, including tetrahydrofurans, tetrahydropyrans, oxepanes, chromans, and dihydrobenzofurans, were obtained in excellent enantioselectivities by reacting the corresponding lactol acetates with diverse enol silanes. Mechanistic studies suggest the reaction to proceed via a nonstabilized, aliphatic, cyclic oxocarbenium ion intermediate paired with the confined chiral counteranion.
- Lee, Sunggi,Kaib, Philip S. J.,List, Benjamin
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- Direct coupling reaction between alcohols and silyl compounds: Enhancement of Lewis acidity of Me3SiBr using InCl3
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The combination of InCl3 and Me3SiBr provided an enhanced Lewis acid system that can be used to promote a wide range of direct coupling reactions between alcohols and silyl nucleophiles in non-halogenated solvents, such as hexane or MeCN. The enhanced Lewis acidity of this system was measured by the 13C NMR in terms of the coordination to an alcohol. Moreover, the interaction between Me3SiBr and the In(III) species was revealed by 29Si NMR spectral analysis. Highly chemoselective allylations toward a hydroxyl moiety over ketone and acetoxy ones have been demonstrated.
- Saito, Takahiro,Nishimoto, Yoshihiro,Yasuda, Makoto,Baba, Akio
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p. 8516 - 8522
(2007/10/03)
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- Reactions of α-Acetoxy-N-nitrosopyrrolidine and α-Acetoxy-N-nitrosopiperidine with Deoxyguanosine: Formation of N2-Tetrahydrofuranyl and N2-Tetrahydropyranyl Adducts
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The goal of this study was to compare the reactions of α-acetoxy-N-nitrosopyrrolidine (α-acetoxyNPYR) and α-acetoxy-N-nitrosopiperidine (α-acetoxyNPIP) with deoxyguanosine (dG). α-AcetoxyNPYR and α-acetoxyNPIP are stable precursors to the α-hydroxynitrosamines which are formed metabolically from NPYR and NPIP. These α-hydroxynitrosamines are believed to be the proximate carcinogens of NPYR and NPIP. NPYR and NPIP, although structurally similar, have remarkably different carcinogenic properties, and a comparison of the reactions of their metabolically activated forms with dG and ultimately DNA could provide insights on their mechanisms of carcinogenicity. Reactions of α-acetoxyNPYR and α-acetoxyNPIP with dG were carried out at 37 deg C and pH 7.0. The products were analyzed by HPLC and characterized by their spectral properties and by comparison to standards. In each reaction, one of the major products was a new type of dG adduct: N2-(tetrahydrofuran-2-yl)dG (THF-dG) from α-acetoxyNPYR and N2-(3,4,5,6-tetrahydro-2H-pyran-2-yl)dG (THP-dG) from α-acetoxyNPIP. THF-dG was synthesized independently by reaction of either 2-chlorotetrahydrofuran or 2,3-dihydrofuran with dG. Similarly, THP-dG was prepared by reaction of 2-chloro-3,4,5,6-tetrahydro-2H-pyran with dG. The structures of THF-dG and THP-dG were established by their UV and 1H-NMR spectra. THF-dG was less stable than THP-dG, but could be readily converted to a stable derivative, N2-(4-hydroxybutyl)dG, by reaction with NaBH4. THF-dG and THP-dG were converted to dG and 2-hydroxytetrahydrofuran or 2-hydroxy-3,4,5,6-tetrahydro-2H-pyran, respectively, upon neutral thermal or acid hydrolysis. This reaction was found to be reversible, with the adducts being produced in substantial amounts by reaction of 2-hydroxytetrahydrofuran or 2-hydroxy-3,4,5,6-tetrahydro-2H-pyran with dG. The latter reaction accounts for part of the THF-dG and THP-dG produced from the α-acetoxynitrosamines; stable oxonium ion-derived electrophiles may also be involved in the formation of THF-dG and THP-dG. Comparisons of the yields of various adducts in the reaction of α-acetoxyNPYR and α-acetoxyNPIP with dG showed some major differences. Whereas yields of THF-dG and THP-dG were similar, adducts formed from open chain diazonium ion or related intermediates were formed more extensively from α-acetoxyNPYR than from α-acetoxyNPIP. Adducts formed from enal products of the two nitrosamines were also different. Adduct formation as characterized in this study may account for some of the contrasting carcinogenic properties of NPYR and NPIP.
- Young-Sciame, Ruth,Wang, Mingyao,Chung, Fung-Lung,Hecht, Stephen S.
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p. 607 - 616
(2007/10/03)
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- Novel 2'-deoxy-5-substituted uridine derivatives, processes for preparing the same and antitumor agent containing the same
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Novel 2'-deoxy-5-substituted uridine derivative represented by the general formula, STR1 wherein R1 is a hydrogen atom, a benzoyl group or a tetrahydrofuranyl group; R2 is a fluorine atom or a trifluoromethyl group; and any one of R
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- Electrochemical Generation of Reactive Nitrogen Species. 10. Anodic Amination of Tetrahydrofuran
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Anodic oxidation in THF of aminyl anions (lithium amides and aminomagnesium bromides) together with free aliphatic amines efficiently afforded 2-aminotetrahydrofurans.A similar reaction took place in the anodic oxidation of N-lithiolactams.These reactions are the first examples of anodic amination of an aliphatic saturated ether.
- Fuchigami, Toshio,Sato, Takashi,Nonaka, Tsutomu
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p. 366 - 369
(2007/10/02)
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- β-Halogeno Ether Synthesis of Olefinic Alcohols: Stereochemistry and Conformation of 2-Substituted 3-Halogenotetrahydro-pyran and furan Precursors
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Ring-scission of cis- or trans-2-alkyl- (or aryl-) 3-chlorotetrahydropyrans proceeds regioselectively and highly stereoselectively to give (E)-alk-4-en-1-ols, but in the parallel tetrahydrofuran series (Z)-/(E)-mixtures, dependent on percursor geometry, are formed.In this paper the stereochemistry and conformation of the tetrahydro-pyran and - furan precursors are considered.The cis/trans-composition of 2,3-dihalogenotetrahydro-pyrans and-furans made by various routes is reported.Reaction with Grignard reagents gives separable cis-/trans-mixtures the stereoisomeric composition of which, in the cases examined, does not depend on the stereoisomeric composition of the dihalide, but does vary with the halogen and the composition of the Grignard or dialkylmagnesium; possible reasons are discussed.The stereochemistry and conformation of the 2-alkyl- (or aryl-)3-chlorotetrahydropyrans is analysed by n.m.r. methods (J2a,3acis ca. 1.5 Hz; J2a,3atrans ca. 9.8 Hz) but assignments for the two tetrahydrofuran series with J2,3 2.6-3.6 and 4.3-5.9 are made uncertain by pseudorotation.The stereochemical identity of the two series is rigorously proved by isolation of cis- and trans-2-allyl-3-chlorotetrahydrofuran.On the one hand the former is hydrogenated to the cis-2-propyl compound, correlated with other members of the alkyl series, but on the other it is oxidised and the acid is converted into the cis-p-bromophenyl ester.The stereochemistry and conformation of the latter is rigorously demonstrated by an X-ray structure.The stereochemistries and conformations of the 2-deuterio- and 2-methoxy-3-chlorotetrahydropyrans are discussed, and consideration is then extended to the 2-alkyl-3-chloro-2-methyltetrahydro-pyran and -furan series.
- Crombie, Leslie,Wyvill, Robert D.
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p. 1971 - 1982
(2007/10/02)
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- Diastereomeric 6-desoxy-6-spiro-α-methylene-γ-butyrolactone derivatives of naltrexone and oxymorphone. Selective irreversible inhibition of naltrexone binding in an opioid receptor preparation by a conformationally restricted Michael acceptor ligand
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The diastereomeric 6-desoxy-6-spiro-α-methylene-γ-butyrolactone derivatives of naltrexone (4a and 5a) and of oxymorphone (4b and 5b) were prepared from their parent ketones. Diastereomers 4a and 4b were obtained from the 3,14-diacetate derivatives of naltrexone and oxymorphone by reaction with the Reformatsky reagent prepared from methyl α-(bromomethyl)acrylate. Deacetylation with methanol completed the synthesis. Diastereomers 5a and 5b were obtained from two oxiranes, respectively. The oxiranes were allowed to react with the sodium salt of ethyl acetoacetate, followed by methenation of and deprotection to complete the synthesis of 5a and 5b, respectively. Compound 5a was the most potent agent tested in competition against [3H]naltrexone in the opioid radioreceptor assay. At a concentration of 5 nM this compound produced a 50% inhibition of binding. The majority of this inhibition (30%) was irreversible, i.e., it remained even after extensive washing of the membrane preparation in the presence and absence of Na+. Naloxone protected against this irreversible effect. The data suggest a receptor nucleophile, perhaps a sulfhydryl group, is located where it can add to the α,β-unsaturated carbonyl system of 5a.
- Koolpe,Nelson,Gioannini l.,Angel,Simon
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p. 1718 - 1723
(2007/10/02)
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