- Construction and activity evaluation of novel dual-target (SE/CYP51) anti-fungal agents containing amide naphthyl structure
-
With the increase of fungal infection and drug resistance, it is becoming an urgent task to discover the highly effective antifungal drugs. In the study, we selected the key ergosterol bio-synthetic enzymes (Squalene epoxidase, SE; 14 α-demethylase, CYP51) as dual-target receptors to guide the construction of novel antifungal compounds, which could achieve the purpose of improving drug efficacy and reducing drug-resistance. Three different series of amide naphthyl compounds were generated through the method of skeleton growth, and their corresponding target products were synthesized. Most of compounds displayed the obvious biological activity against different Candida spp. and Aspergillus fumigatus. Among of them, target compounds 14a-2 and 20b-2 not only possessed the excellent broad-spectrum anti-fungal activity (MIC50, 0.125–2 μg/mL), but also maintained the anti-drug-resistant fungal activity (MIC50, 1–4 μg/mL). Preliminary mechanism study revealed the compounds (14a-2, 20b-2) could block the bio-synthetic pathway of ergosterol by inhibiting the dual-target (SE/CYP51) activity, and this finally caused the cleavage and death of fungal cells. In addition, we also discovered that compounds 14a-2 and 20b-2 with low toxic and side effects could exert the excellent therapeutic effect in mice model of fungal infection, which was worthy for further in-depth study.
- An, Yunfei,Fan, Haiyan,Han, Jun,Liu, Wenxia,Liu, Yating,Sun, Bin,Sun, Zhuang
-
-
- Tuning Triplet Energy Transfer of Hydroxamates as the Nitrene Precursor for Intramolecular C(sp3)-H Amidation
-
Reported herein is the design of a photosensitization strategy to generate triplet nitrenes and its applicability for the intramolecular C-H amidation reactions. Substrate optimization by tuning physical organic parameters according to the proposed energy transfer pathway led us to identify hydroxamates as a convenient nitrene precursor. While more classical nitrene sources, representatively organic azides, were ineffective under the current photosensitization conditions, hydroxamates, which are readily available from alcohols or carboxylic acids, are highly efficient in accessing synthetically valuable 2-oxazolidinones and γ-lactams by visible light. Mechanism studies supported our working hypothesis that the energy transfer path is mainly operative.
- Chang, Sukbok,Jung, Hoimin,Keum, Hyeyun,Kweon, Jeonguk
-
supporting information
p. 5811 - 5818
(2020/04/10)
-
- Method for preparing amino alcohol compound by using halogenated intermediate
-
The invention discloses a method for preparing an amino alcohol compound by utilizing a halogenated intermediate. According to the method, an oxygen-halogen bond can be prepared by utilizing cyclic diacyl peroxide and halogenated salt under an illumination condition, and the oxygen-halogen bond is prone to homolysis under an illumination condition to form an active free radical, so the amino alcohol is finally prepared. The novel method for synthesizing the amino alcohol is high in atom utilization rate, simple in synthesis method and high in yield, so the consumption of halide for reactions with synthesis values is reduced, and the purposes of environmental protection and green chemistry are better achieved.
- -
-
-
- Site-Specific C(sp3)–H Aminations of Imidates and Amidines Enabled by Covalently Tethered Distonic Radical Anions
-
The utilization of N-centered radicals to synthesize nitrogen-containing compounds has attracted considerable attention recently, due to their powerful reactivities and the concomitant construction of C?N bonds. However, the generation and control of N-centered radicals remain particularly challenging. We report a tethering strategy using SOMO-HOMO-converted distonic radical anions for the site-specific aminations of imidates and amidines with aid of the non-covalent interaction. This reaction features a remarkably broad substrate scope and also enables the late-stage functionalization of bioactive molecules. Furthermore, the reaction mechanism is thoroughly investigated through kinetic studies, Raman spectroscopy, electron paramagnetic resonance spectroscopy, and density functional theory calculations, revealing that the aminations likely involve direct homolytic cleavage of N?H bonds and subsequently controllable 1,5 or 1,6 hydrogen atom transfer.
- Fang, Yuanding,Fu, Kang,Shi, Lei,Zhao, Rong,Zhou, Jia
-
supporting information
p. 20682 - 20690
(2020/09/07)
-
- Electrochemical Difunctionalization of Alkenes by a Four-Component Reaction Cascade Mumm Rearrangement: Rapid Access to Functionalized Imides
-
An electrochemical four-component reaction cascade Mumm rearrangement was developed. It is a rare example of in situ generation of O-acyl isoamides for 1,3-(O→N) acyl transfer. Inexpensive, commercially available arylethylenes, aryl or heterocyclic acids, acetonitrile, and alcohols were used as substrates. A wide range of aryl acids and alcohols were tolerated and provided imides in satisfactory yields. Subsequent hydrolysis of imides could be utilized to synthesize valuable amides and β-amino alcohol derivatives.
- Zhang, Xiaofeng,Cui, Ting,Zhao, Xin,Liu, Ping,Sun, Peipei
-
supporting information
p. 3465 - 3469
(2020/02/05)
-
- Aryl olefin azole derivative as well as preparation method and application thereof
-
The invention belongs to the technical field of medicines, and relates to an aryl olefin azole derivative shown in a general formula I, stereoisomers thereof and pharmaceutically acceptable salts, hydrates, solvates or prodrugs thereof, and substituent groups Ar, R and X have definitions given in the specification. The invention also relates to a method for preparing the compound as shown in the general formula I, a medicinal composition containing the compound and application of the compound and the medicinal composition in preparation of medicines for treating and preventing superficial fungal and deep fungal diseases.
- -
-
Paragraph 0065; 0068-0069
(2021/01/15)
-
- Rapid and Quantitative Profiling of Substrate Specificity of ω-Transaminases for Ketones
-
ω-Transaminases (ω-TAs) have gained growing attention owing to their capability for asymmetric synthesis of chiral amines from ketones. Reliable high-throughput activity assay of ω-TAs is essential in carrying out extensive substrate profiling and establishing a robust screening platform. Here we report spectrophotometric and colorimetric methods enabling rapid quantitation of ω-TA activities toward ketones in a 96-well microplate format. The assay methods employ benzylamine, a reactive amino donor for ω-TAs, as a cosubstrate and exploit aldehyde dehydrogenase (ALDH) as a reporter enzyme, leading to formation of benzaldehyde detectable by ALDH owing to concomitant NADH generation. Spectrophotometric substrate profiling of two wild-type ω-TAs of opposite stereoselectivity was carried out at 340 nm with 22 ketones, revealing subtle differences in substrate specificities that were consistent with docking simulation results obtained with cognate amines. Colorimetric readout for naked eye detection of the ω-TA activity was also demonstrated by supplementing the assay mixture with color-developing reagents whose color reaction could be quantified at 580 nm. The colorimetric assay was applied to substrate profiling of an engineered ω-TA for 24 ketones, leading to rapid identification of reactive ketones. The ALDH-based assay is expected to be promising for high-throughput screening of enzyme collections and mutant libraries to fish out the best ω-TA candidate as well as to tailor enzyme properties for efficient amination of a target ketone.
- Han, Sang-Woo,Shin, Jong-Shik
-
p. 3287 - 3295
(2019/06/21)
-
- Borohydride reduction stabilizing system and method for reducing ester into alcohol
-
The invention provides a borohydride reduction stabilizing system and a method for reducing ester into alcohol. The borohydride reduction stabilizing system comprises a borohydride reducing agent anda stabilizer for stabilizing the borohydride reducing agent, wherein the borohydride reducing agent is sodium borohydride or potassium borohydride, and the stabilizer is an alkali metal salt of alcohol. On the basis of an existing sodium borohydride/potassium reducing agent, an alcohol alkali metal salt (such as sodium alcoholate or potassium alcoholate) is added, and then the sodium borohydride/potassium reducing agent can keep stable and is not decomposed under a heating condition, so that on one hand, reduction activity is maintained in a relatively high state and the situation of excessiveuse is reduced, and on the other hand, generation of hydrogen is reduced and the process risk is reduced.
- -
-
Paragraph 0116; 0117; 0118
(2019/09/13)
-
- Montmorillonite K10 catalyzed highly regioselective azidolysis of epoxides: A short and efficient synthesis of phenylglycine
-
A series of β‐hydroxyazides were effectively synthesized from the regioselective ring opening of epoxides by sodium azide using montmorillonite K10 as a novel heterogeneous catalyst in aqueous acetonitrile in good to excellent yields. The utility of this method has been demonstrated by achieving a short synthesis of phenylglycine in 33.5% overall yield.
- Ch Ghosh, Keshab,Banerjee, Isita,Sinha, Surajit
-
p. 2923 - 2934
(2018/12/04)
-
- Directed β C-H Amination of Alcohols via Radical Relay Chaperones
-
A radical-mediated strategy for β C-H amination of alcohols has been developed. This approach employs a radical relay chaperone, which serves as a traceless director that facilitates selective C-H functionalization via 1,5-hydrogen atom transfer (HAT) and enables net incorporation of ammonia at the β carbon of alcohols. The chaperones presented herein enable direct access to imidate radicals, allowing their first use for H atom abstraction. A streamlined protocol enables rapid conversion of alcohols to their β-amino analogs (via in situ conversion of alcohols to imidates, directed C-H amination, and hydrolysis to NH2). Mechanistic experiments indicate HAT is rate-limiting, whereas intramolecular amination is product- and stereo-determining.
- Wappes, Ethan A.,Nakafuku, Kohki M.,Nagib, David A.
-
p. 10204 - 10207
(2017/08/10)
-
- Computer-assisted design, synthesis, binding and cytotoxicity assessments of new 1-(4-(aryl(methyl)amino)butyl)-heterocyclic sigma 1 ligands
-
In this work we applied a blend of computational and synthetic techniques with the aim to design, synthesize, and characterize new σ1 receptor (σ1R) ligands. Starting from the structure of previously reported, high-affinity benzoxazolone-based σ1 ligands, the three-dimensional homology model of the σ1R was exploited for retrieving the molecular determinants to fulfill the optimal pharmacophore requirements. Accordingly, the benzoxazolone moiety was replaced by other heterocyclic scaffolds, the relevant conformational space in the σ1R binding cavity was explored, and the effect on σ1R binding affinity was ultimately assessed. Next, the compounds designed in silico were synthesized, and their affinity and selectivity toward σ1and σ2receptors were tested. Finally, a representative series of best σ1R binders were assayed for cytotoxic activity on the SH-SY5Y human neuroblastoma cell line. Specifically, the new 4-phenyloxazolidin-2-one derivatives 2b (i.e., (R)-2b and (S)-2b) emerged as potential leads for further development as σ1R agents, as they were found endowed with the highest σ1R affinity (Kiσ1 values in the range 0.95–9.3?nM), and showed minimal cytotoxic levels exhibited in the selected, cell-based test, in line with a σ1R agonist behavior.
- Zampieri, Daniele,Vio, Luciano,Fermeglia, Maurizio,Pricl, Sabrina,Wünsch, Bernhard,Schepmann, Dirk,Romano, Maurizio,Mamolo, Maria Grazia,Laurini, Erik
-
p. 712 - 726
(2016/07/06)
-
- Valine amide carbamate derivative containing propargyloxy group and application thereof
-
The invention relates to a valine amide carbamate derivative containing a propargyloxy group and a pharmaceutically acceptable salt thereof, belonging to the field of botanical bactericides. The valine amide carbamate derivative has a general formula (I) as shown in the specification, and the substituent R in the general formula (I) is as defined in the specification. The invention also relates to a preparation method for the compound as shown in the general formula (I), an intermediate specially prepared for development of the compound and application of the compound to prevention and treatment of plant diseases.
- -
-
-
- PRODUCTION METHOD FOR COMPOUND COMPRISING AMINO GROUP AND/OR HYDROXYL GROUP
-
Disclosed is a method for producing a compound having an amino group and/or a hydroxyl group from a substrate compound having an atomic group containing CO or CS by eliminating said atomic group. The substrate compound having an atomic group containing CO or CS (for example, an amide, a carbamate, or the like) is allowed to react with a compound expressed by formula (I) below, at a temperature of 120°C or lower, preferably in the presence of an ammonium salt, to eliminate said atomic group containing CO or CS. In formula (I) A may not be present, and in a case where A is present, A represents an alkyl group having 1 to 6 carbon atoms. ????????H2N-A-NH2?????(I)
- -
-
Paragraph 0091
(2015/01/18)
-
- Observations on the modified wenker synthesis of aziridines and the development of a biphasic system
-
A cheap and reliable process for the modified Wenker cyclization to afford aziridines has been achieved using biphasic conditions for a range of amino alcohol starting materials. A 100 mmol "one-pot" process has also been devised, and the enantiopurity of the starting amino alcohol is retained in the aziridine product.
- Buckley, Benjamin R.,Patel, Anish P.,Wijayantha
-
p. 1289 - 1292
(2013/04/10)
-
- Thermodynamics of phenylacetamides synthesis: Linear free energy relationship with the pK of amine
-
The effective equilibrium constants K′C expressed through the total concentrations of the reagents for the synthesis of N-phenylacetyl-derivatives in aqueous medium from phenylacetic acid and various primary amino compounds have been determined with penicillin acylase as a catalyst. Broad specificity of penicillin acylase (EC 3.5.1.11) to amino components made possible to investigate the acylation of primary amines with different structures and physicochemical properties. Analysis of different components of the effective standard Gibbs energy change ΔGC o′ has revealed favorable thermodynamics for the synthesis of phenylacetamides from unionized substrates forms, however the ionization of reactants carboxy and amino groups in aqueous solutions pushes the equilibrium position to the hydrolysis especially in case of highly basic amines. A linear correlation between the standard Gibbs energy change for amide bond formation from the unionized reagents species and the basicity of amino group was observed: ΔGTo=-3.56pKamine+7.71(kJ/mol). The established linear free energy relationship (LFER) allows to predict the thermodynamic parameters for direct condensation of phenylacetic acid with any amine of known pK. Condensation of phenylacetic acid and amines with pK value within 1.5-8.5 was shown to be thermodynamically favorable in homogeneous aqueous solution. .
- Guranda, Dorel T.,Ushakov, Gennadij A.,Yolkin, Petr G.,Svedas, Vytas K.
-
experimental part
p. 48 - 53
(2012/05/19)
-
- High performance of N -alkoxycarbonyl-imines in triethylborane-mediated tin-free radical addition
-
Triethylborane-mediated tin-free radical alkylation of N-alkoxycarbonyl- imines, such as N-Boc-, N-Cbz-, and N-Teoc-imines, proceeded smoothly at a low temperature (-78 to -20 °C) to give the corresponding adducts in high yield. Although the formation of isocyanate was the major unfavorable reaction at room temperature, a one-pot conversion of N-Boc-imine to N-ethoxycarbonyl-adduct was possible through the corresponding isocyanate generated in situ. The higher performance of N-alkoxycarbonyl-imine than those of N-Ts- and N-PMP-imines is rationalized by a moderate electron-withdrawing character of an alkoxycarbonyl group that makes both addition of alkyl radical and trapping of the resulting aminyl radical by triethylborane efficiently fast.
- Yamada, Ken-Ichi,Konishi, Takehito,Nakano, Mayu,Fujii, Shintaro,Cadou, Romain,Yamamoto, Yasutomo,Tomioka, Kiyoshi
-
experimental part
p. 1547 - 1553
(2012/03/26)
-
- Synthesis, characterisation and cardiac activity of some novel 2,3-substituted-4-phenyl-1,3-oxazolidine derivatives
-
A series of 2,3-substituted-4-phenyl-1,3-oxazolidine derivatives were synthesized from DL-(±)-phenyl glycine. DL-(±)-Phenyl glycine was reduced to the corresponding alcohol, which was then condensed with different aldehydes to form Schiff bases, which are then educed and further condensed with different substituted aldehydes to give the oxazolidine derivatives. The synthesized compounds are characterized by 1H NMR, IR and mass spectral analysis. All the compounds were investigated for cardiac activity while all the compounds show significant activity.
- Gudaprthi, Vijayalakshmi,Bharathi,Omprakash
-
experimental part
p. 765 - 769
(2011/12/16)
-
- N-Nosyl oxaziridines as terminal oxidants in copper(II)-catalyzed olefin oxyaminations
-
We report that N-4-nosyl-3-phenyloxaziridine is an effective terminal oxidant for copper(II)-catalyzed oxyamination recently developed in our labs. This oxaziridine can be prepared on multi-gram scale and is easily purified by recrystallization. The products of oxyamination using this oxaziridine bear protecting groups that can be readily removed in high yields under mild conditions.
- Deporter, Sandra M.,Jacobsen, Ashley C.,Partridge, Katherine M.,Williamson, Kevin S.,Yoon, Tehshik P.
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scheme or table
p. 5223 - 5225
(2010/11/03)
-
- Formal aromatic C-H insertion for stereoselective isoquinolinone synthesis and studies on mechanistic insights into the C-C bond formation
-
(Chemical Equation Presented) Formal aromatic C-H insertion of rhodium(II) carbenoid was intensively investigated to develop a new methodology and probe its mechanism. Contrasting with the previously proposed direct C-H insertion, the mechanism was revealed to be electrophilic aromatic substitution, which was supported by substituent effects on the aromatic ring and a secondary deuterium kinetic isotope effect. Various isoquinolinones were synthesized intramolecularly via six-membered ring formation with high regioand diastereoselectivity, while averting the common Buchner-type reaction. Intermolecularly, dirhodium catalyzed formal aromatic C-H insertion on electron-rich aromatics was also achieved.
- Park, Chan Pil,Nagle, Advait,Cheol, Hwan Yoon,Chen, Chiliu,Kyung, Woon Jung
-
supporting information; scheme or table
p. 6231 - 6236
(2009/12/08)
-
- A catalyst-free, convenient construction of eight-membered [1,4]oxazocane-5,8-dione heterocycles from aminoethanols with divinyl succinate
-
A convenient protocol for the synthesis of [1,4]oxazocane-5,8-dione heterocycles by direct cyclization using 2-substituted aminoethanols and divinyl succinate without any catalysts and additives was established. This strategy is quite simple and effective to obtain eight-membered rings incorporating lactone and lactam functional groups. Georg Thieme Verlag Stuttgart.
- Chen, Wan-Qin,Zhang, Qing-Yi,Liu, Bo-Kai,Wu, Qi,Lin, Xian-Fu
-
scheme or table
p. 1829 - 1832
(2009/04/07)
-
- Heterogeneous raney nickel and cobalt catalysts for racemization and dynamic kinetic resolution of amines
-
Raney metals were studied as heterogeneous catalysts for racemization and dynamic kinetic resolution (DKR) of chiral amines, as an alternative to metals like palladium or ruthenium. Both Raney nickel and cobalt were able to selectively racemize various chiral amines with high selectivity. In the racemization of benzylic primary amines, the minor formation of side products, e.g., secondary amines, can be suppressed by varying the hydrogen pressure. In the racemization of aliphatic amines over Raney catalysts, the selectivity is very high, with the enantiomeric amine as the sole product. DKR of racemic aliphatic amines can be performed with immobilized Candida antarctica lipase B and Raney nickel in one pot; for 2-hexylamine, a yield of 95% of the acetylated amide was achieved, with 97% ee. Attention is devoted to the compatibility of the enzyme and the metal catalyst during the DKR. For benzylic primary amines, a two-pot process is proposed in which the liquid is alternatingly shuttled between two vessels containing the solid racemization catalyst and the biocatalyst. After 4 such cycles, the amide of (R)-1-phenylethylamine was obtained with 94% yield and more than 90% ee.
- Parvulescu, Andrei N.,Jacobs, Pierre A.,De Vos, Dirk E.
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scheme or table
p. 113 - 121
(2009/04/16)
-
- Effective procedure for selective ammonolysis of monosubstituted oxiranes: application to E7389 synthesis
-
A highly effective procedure is reported to synthesize 1,2-aminoalcohols by regio- and chemo-selective ammonolysis of mono-substituted epoxides. Additive- and concentration-effects were studied, revealing that (1) methanesulfonic acid is most effective among the additives tested and (2) formation of bis-adducts is practically eliminated at [C] ≤ 40 mM. The optimum condition thus identified was successfully applied to the final step of the synthesis of potent anti-tumor compound E7389.
- Kaburagi, Yosuke,Kishi, Yoshito
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p. 8967 - 8971
(2008/03/18)
-
- Copper(II)-catalyzed aminohydroxylation of olefins
-
We report a novel copper(II)-catalyzed aminohydroxylation in which both heteroatoms of an N-sulfonyl oxaziridine are added across an alkene in a regioselective fashion. A variety of styrenes and electron-rich alkenes can be aminohydroxylated using this protocol. Preliminary investigations indicate that this new process is a rare non-oxenoid reaction of N-sulfonyl oxaziridines, involving a stepwise, polar mechanism rather than a concerted process. Copyright
- Michaelis, David J.,Shaffer, Christopher J.,Yoon, Tehshik P.
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p. 1866 - 1867
(2007/10/03)
-
- General and facile synthesis of 1,2-amino alcohols
-
Facile preparation of 1,2-amino alcohols has been achieved by the reaction of benzyloxymethyl lithium with imines, which are generated from α-amido sulfones and benzyloxymethyl lithium in situ at -78°C in THF.
- Jung, Doo Young,Ko, Chang Hong,Kim, Yong Hae
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p. 1315 - 1317
(2007/10/03)
-
- Highly Enantioselective Synthesis of 1,2-Amino Alcohol Derivatives via Proline-Catalyzed Mannich Reaction
-
Here we report a new catalytic asymmetric synthesis of oxazolidin-2-ones 4 and Cbz-protected 1,2-amino alcohols 5. Our sequence is based on the chemistry of previously unknown 5-acyloxy-oxazolidin-2-ones, which are obtained via proline-catalyzed direct asymmetric three-component Mannich reaction and Baeyer-Villiger oxidation.
- Pojarliev, Peter,Biller, William T.,Martin, Harry J.,List, Benjamin
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p. 1903 - 1905
(2007/10/03)
-
- New, convenient methods of synthesis and resolution of 1,2-amino alcohols
-
Oximes of α-keto esters are reduced to obtain the corresponding amino alcohols using NaBH4 in combination with I2, CH 3COOH, TiCl4, ZrCl4, COCl2, H 2SO4, and TMS-Cl in 60-85% yields. The racemic phenylglycinol, phenylalaninol, and 2-aminobutanol are resolved using dibenzoyl-L-tartaric acid to obtain enantiomeric samples of >98% ee.
- Periasamy, Mariappan,Sivakumar, Sangarappan,Reddy, Meda Narsi
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p. 1965 - 1967
(2007/10/03)
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- Convenient methods for the hydrolysis of oxazolidinones to vicinal aminoalcohols
-
We have developed two convenient methods for hydrolysis of 2-oxazolidinones to the corresponding vicinal aminoalcohols. N-Substituted oxazolidinones can be readily hydrolyzed using Dowex 1×8-100 resin. N-Unsubstituted oxazolidinones cannot be hydrolyzed using Dowex resins but are effectively hydrolyzed using polymer supported ethylenediamine.
- Katz, Steven J,Bergmeier, Stephen C
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p. 557 - 559
(2007/10/03)
-
- From vicinal azido alcohols to Boc-amino alcohols or oxazolidinones, with trimethylphosphine and Boc2O or CO2
-
A practical solution to the problem of converting directly 1,2-azido alcohols to Boc-amino alcohols, without recourse to catalytic hydrogenation, involves the use of Me3P/Boc2O in THF (or CH2Cl2) and aqueous NaOH at rt (90-98% yields). The same azido alcohols can be converted in one-pot to the corresponding oxazolidinones with Boc2O/DMAP/Me3P or even better with CO2 and Me3P under basic catalysis (91-96% yields).
- Ariza, Xavier,Pineda, Oriol,Urpí, Fèlix,Vilarrasa, Jaume
-
p. 4995 - 4999
(2007/10/03)
-
- Cobalt(II) chloride-catalyzed chemoselective sodium borohydride reduction of azides in water
-
Reduction of azides to amines and amides was carried out with NaBH4/CoCl2·6H2O in sole water at 25 °C under catalytic heterogeneous conditions. A broad spectrum of azides was reduced in a short time, chemoselectively in high yield and purity.
- Fringuelli, Francesco,Pizzo, Ferdinando,Vaccaro, Luigi
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p. 646 - 650
(2007/10/03)
-
- Remarkable dependence of the regioselectivity of free radical additions to 3-cinnamoyloxazolidin-2-ones on the stability of the intermediate adduct-radical, electrophilicity of the adding radicals and the conditions for their generation
-
Electrophilic (CCl3) and nucleophilic radicals (Pri) are found to add at 80°C to the C=C bond of 3-(E)-cinnamoyl-4-phenyloxazolidin-2-one 1a and 3-(E)-cinnamoyl-4-benzyloxazolidin-2-one 1b predominantly at the α-position of the bond. While for the CCl3 radical no product of β-addition has been found, for the Pri radical such a path constitutes up to 40% of the whole process at 80°C. An interplay between the stability of the intermediate adduct radicals and the electrophilicity or nucleophilicity of the radicals undergoing addition are invoked to rationalize the observation. At a low temperature (-23°C) β-addition of the Pri radical becomes the dominant process (up to 75%).
- Tararov, Vitali I.,Kuznetzov, Nikolai Yu.,Bakhmutov, Vladimir I.,Ikonnikov, Nikolai S.,Bubnov, Yuri N.,Khrustalev, Victor N.,Saveleva, Tatiana F.,Belokon, Yuri N.
-
p. 3101 - 3106
(2007/10/03)
-
- Regio and stereocontrolled synthesis of aryl cis aminoalcohols from cis glycols
-
Reaction of aryl substituted cis diols with α-acetoxyisobutyryl chloride results in the formation of trans vicinal chlorohydrin acetates where the halide is benzylic. Displacement of chloride with azide ion, deprotection of the ester and reduction of the azide furnishes the requisite cis aminoalcohols. This facile four-step procedure results in the exclusive replacement of a benzylic hydroxyl with an amino group, with a net retention of stereochemistry. This set of transformations is generally applicable to a wide variety of cis diols, and the overall yields are excellent.
- Lakshman, Mahesh K.,Zajc, Barbara
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p. 2529 - 2532
(2007/10/03)
-
- On the mechanism of the Fe(CO)5-catalyzed Kharasch reaction 1. Stereochemistry of addition of BrCCl3 to (R)-3-(E)-cinnamoyl-4-phenyloxazolidin-2-one, (R)-3-(E)-acryloyl-4-phenyloxazolidin-2-one, and their π-complexes with Fe(CO)4
-
Regioselectivity and diastereoselectivity of the addition of BrCCl3 to (R)-3-(E)-cinnamoyl-4-phenyloxazolidin-2-one (1) and (R)-3-(E)-acryloyl-4-phenyloxazolidin-2-one (2) catalyzed by Fe(CO)5 or initiated with benzoyl peroxide were investigated. Stereochemistry of the reaction of BrCCl3 with the π-complexes (4R,αS,βS)-η 2-(3-(E)-cinnamoyl-4-phenyl-oxazolidin-2-one)irontetracarbonyl (3a) and (4R,αR)-η 2-(3-acryloyl-4-phenyloxazolidin-2-one)irontetracarbonyl (4b) was also studied. The results obtained allow the following conclusions to be drawn: (1) the thermal Kharasch reaction catalyzed by Fe(CO)5 proceeds by a redox catalysis mechanism; (2) iron (in any of its oxidation states) is not coordinated to olefins in the transition state of the reaction; (3) the transfer of the halogen atom on the radical adduct probably occurs inside a radical-iron cation pair.
- Tararov,Savel'eva,Struchkov,Pisarevskii,Raevskii,Belokon'
-
p. 600 - 609
(2007/10/03)
-
- Synthesis of methyl 2-(fluoromethyl)-3-fluoroalanine
-
The title compound 1b, an important intracellular pH indicator, is conveniently prepared in 44% overall yield from 1,3-difluoro-2-propanol (2). Key steps in this synthesis include oxidation of 2 to 1,3-difluoroacetone (3) in near quantitative yield using KMnO4/CuSO4 and the addition of trimethylsilyl cyanide to a phenyl glycinol protected imine. The efficiency of this process was enhanced further by use of crude reaction mixtures of their solutions.
- Davis,Reddy,Bental,Deutsch
-
p. 701 - 702
(2007/10/02)
-
- HIGHLY REGIO AND CHEMOSELECTIVE RING OPENING OF EPOXIDES WITH TRIMETHYLSILYL AZIDE IN THE PRESENCE OF ALUMINIUM ISOPROPOXIDE AND TITANIUM ISOPROPOXIDE
-
The ring-opening of functionalized epoxides with trimethylsilyl azide in the presence of a catalytic amount of Ti(O-i-Pr)4 or Al(O-i-Pr)3 is described.The reaction is stereospecific and highly regiospecific, leading generally to the formation of the carbon-azido bond on the less substituted carbon.The mechanism of this reaction is also discussed.
- Sutowardoyo, Kun I.,Emziane, Mohamed,Lhoste, Paul,Sinou, Denis
-
p. 1435 - 1446
(2007/10/02)
-
- Diastereoselectivity of Organometallic Additions to Nitrones Bearing Sterogenic N-Substituents
-
The diastereoselectivity of organometallic additions to nitrones bearing stereogenic α-arylethyl, β-methoxyalkyl, and β-(silyloxy)alkyl substituents on nitrogen has been investigated.High and complementary diastereoselectivity (90-94percent) was observed in the additions of Grignard reagents to nitrones (e.g. 22 and 23) bearing the potentially chelating β-methoxyalkyl group.However, the opposite selectivity resulted from the reaction of methylmagnesium bromide with the corresponding silyl ether (27).The relative stereochemistry of selected hydroxylamine adducts wasestablished by reduction of their phosphate and carbonate derivatives to known amines (37a,b and 39), by periodate cleavage of a β-hydroxy hydroxylamine (41b), and by various correlations (Scheme II).The high facial diastereoselectivity observed with the N-(β-methoxyalkyl)nitrones is explained by a simple chelation model (Scheme III).
- Chang, Zen-Yu,Coates, Robert M.
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p. 3464 - 3474
(2007/10/02)
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- Preparation of α-(N-Trimethylsilyl)imino Esters and Their Use ih the Synthesis of α-Amino Esters and 2-Alkoxycarbonylimidazol-4(2H)-ones
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The reaction of α-keto esters with lithium 1,1,1,3,3,3-hexamethyldisilazanide afforded α-(N-trimethylsilyl)imino esters in good yields, which were reduced to the corresponding α-amino esters by reducing agents such as NaBH3CN. α-(N-Trimethylsilyl)imino esters were treated with methanol to afford 2-alkoxycarbonylimidazole-4(2H)-ones via dimerization of the intermediate α-imino esters.
- Matsuda, Yoshihiko,Tanimoto, Shigeo,Okamoto, Tadashi,Ali, Syed Mashhood
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p. 279 - 281
(2007/10/02)
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- Improved Chiral Derivatizing Agents for the Chromatographic Resolution of Racemic Primary Amines
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Several 4- and/or 5-aryl-substituted 2-oxazolidones have been prepared and studied as chiral derivatizing agents (CDA) for the chromatographic resolution of chiral primary amines via diastereomeric allophanates.The diastereomeric allophanates derived from either racemic primary amines and cis-4,5-diphenyl-2-oxazolidone-3-carbamyl chloride or racemic isocyanates and cis-4,5-diphenyl-2-oxazolidone show sufficient NMR chemical shift differences and chromatographic separability that this heterocyclic system should prove to be a very useful CDA for the chromatographic resolution and determination of the absolute configuration of a variety of chiral primary amines.The diastereomeric allophanates are readily hydrolyzed to return both chiral components of the allophanates in excellent yield.Both solution and adsorbed conformations of these allophanates are discussed in reference to the determination of the absolute configuration of the allophanates (and hence of the chiral primary amine) from the senses of NMR nonequivalence between and chromatographic elution order of the diastereomers.
- Pirkle, William H.,Simmons, Kirk A.
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p. 2520 - 2527
(2007/10/02)
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- Ueber die Stereoselektivitaet der 9,9'-Spirobifluoren-kronenaether gegenueber α-Aminoalkoholen
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Crown ethers I-VI were tested by partition experiments for their stereoselectivity towards α-amino alcohols 1-10.The stereoselectivity depends in a regular way on both the absolute and relative configuration of the crown ether and α-amino alcohol.Comments are made on some high stereoselectivities.
- Prelog, Vladimir,Mutak, Stjepan
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p. 2274 - 2278
(2007/10/02)
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- ONE STEP SYNTHESIS OF AZIRIDINES BY THE MICHAEL TYPE ADDITION OF FREE SULFIMIDES
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The Michael type additions of diphenyl N-unsubstituted sulfimide (free sulfimide) to various electrophilic olefins were carried out.The reaction with cis- and trans-dibenzoylethylene, dimethylfumarate, dimethylmaleate, benzalacetophenone and benzalacetone gave mainly the corresponding trans-2-acylaziridines and trans-enaminoketones.However, phenyl vinyl sulfone or acrylonitrile afforded not the corresponding aziridine but diphenyl-N-2-cyano or N-2-phenylsulfonylethylsulfimide, a simple Michael adduct.When optically active (+)-(R)-o-methoxyphenylphenyl free sulfimide was treated with such an α,β-unsaturated carbonyl compound as benzalacetophenone, an optically active 2-acylaziridine, i.e., (-)-trans-2-benzoyl-3-phenylaziridine was obtained in ca 30percent optical purity and its absolute configuration was assigned as (2R,3S) upon chemical transformation to the configurationally known 2-phenyl-2-benzoylamino-1-ethanol or by comparing its CD spectrum with that of (1R,2R)-1-phenyl-2-benzoyl-cyclopropane.Meanwhile, (-)-(S)-o-methoxyphenylphenyl free sulfimide was found to react with benzalacetophenone to afford (+)-trans-2-benzoyl-3-phenylaziridine of 25percent optical purity.Effects of solvent and temperature on both the distribution of the products ratio and the optical yield were examined.
- Furukawa, Naomichi,Yoshimura, Toshiaki,Ohtsu, Masami,Akasaka, Takeshi,Oae, Shigeru
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