Carbocyclische Verbindungen aus Monosacchariden. I. Umsetzungen in der glucosereihe

Carbocyclic Compounds from Monosaccharides. 1. Transformations in the Glucose Series A method for the preparation of pentasubstituted cyclopentanes from monosaccharides is presented, involving two crucial steps, viz. the reductive fragmentation of 5-bromo-5-deoxyglucosides (such as 10, 17 and 23 , see Scheme 3) with Zn or butyl lithium yielding 5,6-dideoxy-hex-5-enoses (such as 11 and 24 , see Schemes 3 and 4), and the subsequent cyclization of these hexenoses with N-methyl- or N-(alkoxyalkyl)hydroxylamines (via the corresponding nitrones) to form cyclopentano-isoxazolidines (see Scheme 2). Thus, the glucosides 17 and 23 were converted diastereoselectively and in good yields into the cyclopentano-isoxazolidines 27 and 45 (Schemes 5 and 7), which were characterized by their transformation into various derivatives. 27 and 45 were correlated through the common derivative 62 . The configuration of the cyclization products were established by pyrolysis of the N-oxide 65 to the enol ether 67 (Scheme 10).     

Protective effects of cyanidin-3-O-beta-glucopyranoside against UVA-induced oxidative stress in human keratinocytes

Ultraviolet-A (UVA) radiation causes significant oxidative stress because it leads to the generation of reactive oxygen species (ROS), leading to extensive cellular damage and eventual cell death either by apoptosis or necrosis. We evaluated the protective effects of cyanidin-3-O-beta-glucopyranoside (C-3-G) against UVA-induced apoptosis and DNA fragmentation in a human keratinocyte cell line (HaCaT). Treatment of HaCaT cells with C-3-G before UVA irradiation inhibited the formation of apoptotic cells (61%) and DNA fragmentation (54%). We also investigated antioxidant properties of C-3-G in HaCaT cells against ROS formation at apoptotic doses of UVA; C-3-G inhibited hydrogen peroxide (H2O2) release (an indicator of cellular ROS formation) after UVA irradiation. Further confirmation of the potential of C-3-G to counteract UVA-induced ROS formation comes from our demonstration of its ability to enhance the resistance of HaCaT cells to the apoptotic effects of both H2O2 and the superoxide anion (O2*-), two ROS involved in UVA-oxidative stress. Furthermore, in terms of Trolox Equivalent Antioxidant Activity, C-3-G treatment led to a greater increase in antioxidant activity in the membrane-enriched fraction than in the cytosol (55% vs 19%). The protective effects against UVA-induced ROS formation can be attributed to the higher membrane levels of C-3-G incorporation. These encouraging in vitro results support further research into C-3-G (and other anthocyanins) as novel agents for skin photoprotection.     

Glycosylidene Carbenes. Part 6. Synthesis of alkyl and fluoroalkyl glycosides

The syntheses of glycosides from the diazirine 1 and a range of alcohols under thermal and/or photolytic conditions are described. Yields and diastereoselectivities depend upon the pK_HA values of the alcohols, the solvent, and the reaction temperature. The glycosidation of weakly acidic alcohols (MeOH, EtOH, i-PrOH, and t-BuOH, 1 equiv. each) in CH₂Cl₂ at room temperature leads to the glycosides 2–5 in yields between 60 and 34% (Scheme 1 and Table 1). At ?70 to ?60°, yields are markedly higher. In CH₂Cl₂, diastereoselectivities are very low. In THF, at ?70 to ?60°, however, glycosidation of i-PrOH leads to α-D -/β-D - 4 in a ratio of 8:92. More strongly acidic alcohols, such as CF₃CH₂OH, (CF₃)₂ CHOH, and (CF₃)₂C(Me)OH, and the highly fluorinated long-chain alcohols CF₃(CF₂)₅(CH₂)₂OH ( 11 ) and CHF₂(CF₂)₉CH₂OH ( 13 ) react (CH₂Cl₂, r.t.) in yields between 73 and 85% and lead mainly to the β-D -glucosides β-D - 6 to β-D - 8 , β-D - 12 , and β-D - 14 (d.e. 14–68%). Yields and diastereoselectivities are markedly improved, when toluene, dioxane, 1,2-dimetoxyethane, or THF are used, as examined for the glycosidation of (CF₃)₂C(Me)OH, yielding (1,2-dimethoxyethane, 25°) 80% of α-D -/ β-D - 8 in a ratio of 2:98 (d.e. 96%; Table 4). In EtCN, (CF₃)₂C(Me)OH yields up to 55% of the imidate 10 . Glycosidation of di-O-isopropylideneglucose 15 leads to 16 (CH₂Cl₂, r.t.; 65%, α-D / β-D = 33:67). That glycosidation occurs by initial protonation of the intermediate glycosylidene carbene is evidenced, for strongly acidic alcohols, by the formation of 10 , derived from the attack of (CF₃)₂MeCO^? on an intermediate nitrilium ion (Scheme 4), and for weakly acidic alcohols, by the formation of α-D - 9 and β-D - 9 , derived by attack of i-PrO^? on intermediate tetrahydrofuranylium ions. A working hypothesis is presented (Scheme 3). The diastereoselectivities are rationalized on the basis of a protonation in the σ plane of the intermediate carbene, the stabilization of the thereby generated ion pair by interaction with the BnO? C(2) group, with the solvent, and/or with the alcohol, and the final nucleophilic attack by RO^? in the π plane of the (solvated) oxonium ion.     

Disruption of DNA repair processes by carcinogenic metal compounds

Based on pronounced enhancing effects in combination with other DNA-damaging agents the potentials of Ni(II), Cd(II) and As(III) to interfere with DNA repair processes in HeLa cells was investigated. With respect to oxidative DNA damage, Ni(II) and Cd(II) induced DNA strand breaks starting at concentrations of 250 μM and 5 μM, respectively. The induction of oxidative DNA base modifications like 8-hydroxyguanine was restricted to the cytotoxic concentration of 750 μM Ni(II) and not observed after treatment with Cd(II). In contrast, the removal of oxidative DNA base modifications was inhibited at concentrations as low as 50 μM Ni(II) and 0.5 μM Cd(II). Regarding nucleotide excision repair, Ni(II) and Cd(II) disturbed the DNA-protein interactions involved in the damage recognition step when applying HeLa nuclear protein extracts and a UV-damaged oligonucleotide, while As(III) inhibited the actual incision event. In the case of Ni(II) and Cd(II), this effect was reversible by the addition of Mg(II) and Zn(II), respectively. Furthermore, Cd(II) inactivated the isolated bacterial Fpg protein, most likely by the displacement of Zn(II) from its zinc finger structure. Since DNA is continuously damaged by exogenous and endogenous sources, an impaired repair capacity might well account for the carcinogenic action of the metal compounds. Received: 30 July 1997 / Revised: 6 October 1997 / Accepted: 10 October 1997     

Analogues of Sialic Acids as Potential Sialidase Inhibitors Synthesis of 2-C-Hydroxymethyl Derivatives of N-Acetyl-6-amino-2,6-dideoxy-neuraminic Acid

The intramolecular cycloaddition of the previously described azidoalkene 16 , the related diacetates 7 and 13 , and the monoacetate 8 led diastereoselectivity to the (2R)- and (2S)-configurated hydropyridotriazoles 17 , 9 and 11 , 14 and 15 , and 10 and 12 , respectively (Scheme 1). Thermolysis of 16 gave also the aziridine 18 , its proportion increasing with reaction time. The diastereoselectivity of the cycloaddition- is rationalized on the basis of steric interactions and of H? bonds in the transition state. Photolysis in benzene partially transformed 9 into the aziridine 19 . Treatment of 9 with aqueous AcOH gave 19 and the tetrahydrofuran 20 , with AcOH in benzene 20 and the triacetate 23 , and with aqueous H₂SO₄ in THF, the primary alcohol 22 (room temperature) or 19 and 22 (0°). Deacetylation of 9 followed by reaction with pyridinium hydrochloride led to the tetrahydrofuran 21 and the chloride 24 (Scheme 2). The diacetate 22 and the triacetate 23 gave the tripl 25 which was deprotected to 26 . Reduction of the keto-aziridine 18 (NaBH₄) gave the alcohols 27 and 29 which were acetylated to give 28 and 19 , respectively (Scheme 3). Treatment of the aziridine 28 with AcOH in benzene followed by deacetylation gave 30 and hence 31 . AcOH in benzene transformed the triazoline 15 first into the aziridine 32 and hence into 33 , which was deprotected to give the triol 34 and hence 35 . The 2-(hydroxymethyl)piperidines 26 , 31 , and 35 inhibited Vibrio cholerae sialidase with K₁ = 3.8 · 10^?2 M, 3.4 · 10^?3 M, and 1.5 · 10^?4 M, respectively. The conformation of the glycerol side chain of these compounds and of the unbranched piperidines 2–4 deviates from the one of Neu5Ac (and Neu2en5Ac). This finding is rationalized by an H-bond between OH? C(8) and NH? C(6). The conformations and the K₁ values of 26 , 31 , and 35 correlate with each other.     

Disorder effects in Mn12–acetate at 83 K

The structure of hexadeca‐μ‐acetato‐tetra­aqua­dodeca‐μ₃‐oxo‐dodecamanganese bis(acetic acid) tetrahydrate, [Mn₁₂O₁₂(CH₃COO)₁₆(H₂O)₄]·2CH₃COOH·4H₂O, known as Mn₁₂–acetate, has been determined at 83 (2) K by X‐ray diffraction methods. The fourfold (S₄) molecular symmetry is disrupted by a strong hydrogen‐bonding interaction with the disordered acetic acid mol­ecule of solvation, which displaces one of the acetate ligands in the cluster. Up to six Mn₁₂ isomers are potentially present in the crystal lattice, which differ in the number and arrangement of hydrogen‐bonded acetic acid mol­ecules. These results considerably improve the structural information available on this molecular nanomagnet, which was first synthesized and characterized by Lis [Acta Cryst. (1980), B 36 , 2042–2046].     

Localization of a multiblock copolymer at a selective interface: scaling predictions and Monte Carlo verification

We investigate the localization of a hydrophobic-polar regular copolymer at a selective solvent-solvent interface with emphasis on the impact of block length M on the copolymer behavior. The considerations are based on simple scaling arguments and use the mapping of the problem onto a homopolymer adsorption problem. The resulting scaling relations treat the gyration radius of the copolymer chain perpendicular and parallel to the interface in terms of chain length N and block size M, as well as the selectivity parameter chi. The scaling relations differ for the case of weak and strong localization. In the strong localization limit a scaling relation for the lateral diffusion coefficient D( parallel) is also derived. We implement a dynamic off-lattice Monte Carlo model to verify these scaling predictions. For chain lengths in a wide range (32相似文献   

Reaction of N,N'-dialkyldithiodianilines with β-ketoesters. A new synthesis of N-alkyl-2-acyl-3-oxo-3,4-dihydro-1,4-benzothiazines

The title compounds 3a-j together with the N-alkylacylketene S,N-acetals 12a-j were obtained by reaction of N,N'-dialkyldithiodianilines with β-ketoesters compounds. A possible reaction pathway is suggested.     

Asymmetric Information in a Capital Accumulation Differential Game with Spillover and Learning Effects

Journal of Optimization Theory and Applications - This paper considers a capital accumulation game where the installation costs of investments are lowered by the firm’s own capital stock...