- Stereoselective Yang cyclizations of α-amido ketones
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The photocyclization of methyl-substituted α-acetamido butyrophenone derivatives is highly stereoselective and leads to 2-aminocyclobutanols with complete control of three new stereogenic centers.
- Griesbeck, Axel G.,Heckroth, Heike,Lex, Johann
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- Natural products as sources of new fungicides (V): Design and synthesis of acetophenone derivatives against phytopathogenic fungi in vitro and in vivo
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A series of acetophenone derivatives (10a–10i, 11, 12a–12g, 13a–13g, 14a–14d and 15a–15l) were designed, synthesized and evaluated for antifungal activities in vitro and in vivo. The antifungal activities of 53 compounds were tested against several plant pathogens, and their structure–activity relationship was summarized. Compounds 10a–10f displayed better antifungal effects than two reference fungicides. Interestingly, the most potent compound 10d exhibited antifungal properties against Cytospora sp., Botrytis cinerea, Magnaporthe grisea, with IC50 values of 6.0–22.6 μg/mL, especially Cytospora sp. (IC50 = 6.0 μg/mL). In the in vivo antifungal assays, 10d displayed the significant protective efficacy of 55.3% to Botrytis cinerea and 73.1% to Cytospora sp. The findings indicated that 10d may act as a potential pesticide lead compound that merits further investigation.
- Dan, Wen-Jia,Tuong, Thi-Mai-Luong,Wang, Da-Cheng,Li, Ding,Zhang, An-Ling,Gao, Jin-Ming
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p. 2861 - 2864
(2018/07/25)
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- Catalytic transformation of esters of 1,2-azido alcohols into α-amido ketones
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The esters of 1,2-azido alcohols were transformed into α-amido ketones without external oxidants through the Ru-catalyzed formation of N-H imines with the liberation of N2 followed by intramolecular migration of the acyl moiety. A wide range of α-amido ketones were obtained, and one-pot transformation into the corresponding oxazoles (or a thiazole) was demonstrated.
- Kim, Yongjin,Pak, Han Kyu,Rhee, Young Ho,Park, Jaiwook
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p. 6549 - 6552
(2016/06/01)
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- Probing the 'bipolar' nature of the carbonic anhydrase active site: Aromatic sulfonamides containing 1,3-oxazol-5-yl moiety as picomolar inhibitors of cytosolic CA I and CA II isoforms
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Abstract A series of potent inhibitors of human carbonic anhydrase (CA) isoforms I and II has been prepared via a direct, chemoselective sulfochlorination of a range of 1,3-oxazolyl benzenes and thiophenes, followed by primary sulfonamide synthesis. The latter functionality is a known zinc-binding group (ZBG) responsible for anchoring the inhibitors to the CA's zinc metal ion. The compound's periphery as well as the overall scaffold geometry was designed to enable optimal interactions with the two distinct sides of the enzyme's active site, one of which is lined with hydrophobic residues and while the other is predominantly hydrophilic. As a result, several compounds inhibiting the therapeutically important cytosolic CA I and CA II in picomolar range have been identified. These compounds are one of the most potent CA inhibitors identified to-date. Not only the remarkable (>10 000-fold), cytosolic CA I and CA II selectivity vs. the membrane-bound CA IX and CA XII isoforms, but also the pronounced CA II/I selectivity observed in some cases, allow considering this series as a set of isoform-selective chemical biology tools and promising starting points for drug candidate development.
- Krasavin, Mikhail,Korsakov, Mikhail,Dorogov, Mikhail,Tuccinardi, Tiziano,Dedeoglu, Nurcan,Supuran, Claudiu T.
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p. 334 - 347
(2015/07/28)
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- α-Carbonyl substituent effect on the lifetimes of triplet 1,4-biradicals from norrish-type-II reactions
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Triplet 1,4-biradicals were generated by Norrish-Type-II hydrogen transfer from cx-heteroatom-substituted -branched butyrophenones 1-6 and detected by laser flash absorption measurements. For three oxy-substituted compounds 2-4 (Rα = OH, OCOMe,
- Cai, Xichen,Cygon, Peter,Goldfuss, Bernd,Griesbeck, Axel G.,Heckroth, Heike,Fujitsuka, Mamoru,Majima, Tetsuro
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p. 4662 - 4667
(2008/03/13)
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- Stereoselective synthesis of 2-aminocyclobutanols via photocyclization of α-amido alkylaryl ketones: Mechanistic implications for the Norrish/Yang reaction
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A series of chiral N-acylated α-amino p-methylbutyrophenone derivatives 1a-1h was synthesized from α-amino acids via a three-step procedure. These substrates were photolyzed in benzene and gave Norrish II and Norrish I cleavage products as well as the N-acylated 2-aminocyclobutanols that derive from γ-hydrogen abstraction and 1,4-triplet biradical combination (Yang cyclization). The products were formed with characteristic Yang/cleavage ratios. The quantum yields for the photodecomposition of the N-acetyl-protected substrates 1b,e,f were moderate (12-26%); the diastereoselectivities of the cyclobutanol formation were remarkably high for all substrates. High diastereospecificity was observed for the isoleucine derivatives (2S,3S)-1g and allo-(2S,3R)-1g; the Yang reaction dominated the photochemistry of allo-1g, whereas 1g gave preferentially Norrish II cleavage. The role of hydrogen bonding as one of the stereo-directing effects was demonstrated by comparison of the cyclization efficiency of the valine derivative 1e with 1h,i,j. Also, aromatic β-keto esters gave the Yang cyclization products in low yields. The diastereoselectivity of the cyclobutanol formation was rationalized by a three-step mechanism where every step is connected with one distinct stereochemical induction mechanism: (a) diastereoselective hydrogen abstraction, (b) conformational equilibration of the 1,4-tetramethylene biradicals (as calculated by semiempiric methods) controlled by hydrogen bonding, and (c) diastereoselective biradical combination (versus cleavage) influenced by spin-orbit coupling controlled intersystem crossing geometries.
- Griesbeck, Axel G.,Heckroth, Heike
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p. 396 - 403
(2007/10/03)
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- Keto-enol/enolate equilibria in the N-acetylamino-p-methylacetophenone system. Effect of a β-nitrogen substituent
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The cis-enol of N-acetylamino-p-methylacetophenone was generated flash photolytically and its rates of ketonization in aqueous HClO4 and NaOH solutions as well as in HCO2H, CH3CO2H, H2PO4-, (CH2OH)3CNH3+, and NH4+ buffers were measured. Rates of enolization of N-acetylamino-p-methylacetophenone to the cis-enol were also measured by hydrogen exchange of its methylene protons, and combination of the enolization and ketonization data gave the keto - enol equilibrium constant pKE = 5.33, the acidity constant of the enol ionizing as an oxygen acid pQaE = 9.12, and the acidity constant of the ketone ionizing as a carbon acid pQaK = 14.45. Comparison of these results with corresponding values for p-methylacetophenone itself shows that the N-acetylamino substituent raises all three of these equilibrium constants: KE by 3 orders of magnitude, QaE by 1 order of magnitude, and QaK by 4 orders of magnitude. This substituent also retards the rate of H+ catalyzed enol ketonization by 4 orders of magnitude. The origins of these substituent effects are discussed.
- Chiang,Griesbeck,Heckroth,Hellrung,Kresge,Meng,O'Donoghue,Richard,Wirz
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p. 8979 - 8984
(2007/10/03)
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- Baker's Yeast Reduction of α-(Acylamino)acetophenones and Lipase Catalyzed Resolution of 2-Acylamino-1-arylethanols
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Enzymatic reduction of α-acylaminoacetophenones with fermenting baker's yeast afforded optically active (R)-2-acylamino-1-arylethanols.Furthermore, lipase-catalyzed resolution of the 2-acylamino-1-arylethanols using vinyl acetate as an acyl donor resulted in the formation of (S)-1-acetoxy-2-acylamino-1-arylethanols and (R)-2-acylamino-1-arylethanols.
- Izumi, Taeko,Fukaya, Katsumi
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p. 1216 - 1221
(2007/10/02)
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- Cathodic Reduction of Aliphatic Azides and of Azides, Activated by Olefinic and Carbonyl Groups
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In the majority of compounds investigated the main reduction path starting from azido compounds under parotic conditions leads to the retainment of one nitrogen in the product molecules, provided an initial phase of consumption of residual water is overcome.Good to excellent yields of N-acylated or nicely stable N,N-diacetylated aminoderivatives are obtainable.Even a secondary position of the original N3-group prevents diacetylation completely by steric reasons.Vicinal halogen cause the loss of all nitrogen atoms as does the presence of H+ in the case of azidocarbonyl compounds.Where reduction potential of the starting azide lies within the reduction range of Ac2O even high chemical yields of aminoderivatives are obtainable but with decrease of current efficiency.Reductive acetylation of benzoyl azide leads to the isolation of both rotational isomers of N-acetylbenzamide. - Keywords: Unsaturated Azides and Amines; α-Azido- and α-Aminocarbonylcompounds; Cathodic reduction
- Knittel, Dierk
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p. 679 - 688
(2007/10/02)
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- Process for producing threo-3-amino-2-hydroxybutanoyl-aminoacetic acids, as well as novel intermediated therefor and process for producing them
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A process for producing threo-3-amino-2-hydroxybutanoylaminoacetic acids comprises the steps of allowing to react a starting compound represented by the general formula: STR1 wherein R1 represents a naphthyl or a group of the formula: STR2 in which R6 and R7 represent individually hydrogen, halogen, amino or a protected amino, hydroxy or a protected hydroxy, a lower alkoxy or a lower alkyl and R2 represents a protected amino, with a starting compound represented by the general formula: STR3 wherein R3 represents hydrogen or an ester residue, to obtain threo-3-protected amino-2-hydroxy-4-oxobutanoic acid or its ester represented by the general formula: STR4 wherein R1, R2 and R3 have the same meanings as above, and then reducing the same into threo-3-protected amino-2-hydroxybutanoic acid or its ester represented by the general formula: STR5 wherein R1, R2 and R3 have the same meanings as above, and further converting the above compound into 3-amino-2-hydroxybutanoic acid represented by the general formula: STR6 wherein R2 ' represents amino or a protected amino, thereafter condensing the same, in a conventional manner for forming a peptide coupling, with a compound represented by the general formula: STR7 wherein R4 represents an alkyl having 3-4 carbon atom or 3-guanidinopropyl, while previously protecting as required those groups not relevant to the reaction, and removing the protecting groups for the functional groups to produce threo-3-amino-2-hydroxybutanoylaminoacetic acids represented by the general formula: STR8 wherein R1 and R4 have the same meanings as above. This invention also provides the compounds represented by the general formula (III) as novel intermediates for the above aimed compounds and a process for producing the intermediates.
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