- Mechanistic studies in the radical induced DNA strand cleavage - Formation and reactivity of the radical cation intermediate
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In order to understand the heterolytic cleavage of 4'-DNA radical 1 and the regioselective attack of nucleophiles at the intermediate DNA radical cation 3, the chemistry of model radical 8 was studied. It turned out that the heterolytic cleavage in water is favored over homolysis because of the effective solvation of the ions 9 and 10. The regioselectivity of the nucleophilic attack at radical cation 10 can be explained with the valence bond configuration mixing (VBCM) model. (C) 2000 Elsevier Science Ltd.
- Glatthar, Ralf,Spichty, Martin,Gugger, Andreas,Batra, Rohit,Damm, Wolfgang,Mohr, Matthias,Zipse, Hendrik,Giese, Bernd
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Read Online
- AMIDOPYRIMIDONE DERIVATIVES
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The present invention provides compounds of formula I or II: wherein X1, X3, R1, R2, R3, R4 and R5 are as described herein, as well as pharmaceutically acceptable salts thereof.
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Page/Page column 63
(2022/01/06)
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- A 2-methyl-3-tetrahydrofuran thiol acetate method for preparing trans isomer
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The invention relates to a simple preparation method for a 2-methyl-3-tetrahydrofuranthiol acetate cis-trans-isomer which has the structural formula as shown in the specification. The simple preparation method comprises the following steps: propionaldehyde and propandioic acid are subjected to condensation through Knoevenagel to obtain (E)-3-pentenoic acid, the (E)-3-pentenoic acid is reduced through lithium aluminum hydride to obtain (E)-3-pentene-1-alcohol, and then the (E)-3-pentene-1- alcohol reacts with methylsulfonyl chloride to obtain (E)-3-pentene-1-alcohol methanesulfonate, wherein the three-step overall reaction yield is 24%; (E)-3-pentene-1-alcohol methanesulfonate is oxidized with hydrogen peroxide and methanoic acid, and are cyclizated under the alkaline condition to obtain trans-2- methyl-3-hydroxytetrahydrofuran, and hydroxyl is transformed into methanesulfonate which reacts with thioacetic acid to obtain cis-2-methyl-3-tetrahydrofuranthiol acetate, wherein the three-step overall reaction yield is 61%; (E)-3-pentene-1-alcohol methanesulfonate is oxidized with potassium permanganate to obtain cis-2-methyl-3-hydroxytetrahydrofuran, and hydroxyl is transformed into methanesulfonate which reacts with thioacetic acid to obtain trans-2-methyl-3-tetrahydrofuranthiol acetate, wherein the three-step overall reaction yield is 63%.
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Paragraph 0022; 0023
(2016/12/01)
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- Enantioselective syntheses and sensory properties of 2-methyl-tetrahydrofuran-3-thiol acetates
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The enantioselective synthesis of four stereoisomers of 2-methyl-tetrahydrofuran-3-thiol acetate was achieved. The two enantiomers of the important intermediate cis-2-methyl-3-hydroxy-tetrahydrofuran were obtained by Sharpless asymmetric dihydroxylation (AD), whereas the two enantiomers of trans-2-methyl-3-hydroxy-tetrahydrofuran were derived from the corresponding optically active cis-isomers by Mitsunobu reaction. Each stereoisomer of 2-methyl-3-hydroxy-tetrahydrofuran went through mesylation and nucleophilic substitution to afford the corresponding product with specific configuration. (2R,3S)- and (2R,3R)-2-methyl-tetrahydrofuran-3-thiol acetate were obtained in 80% ee, whereas the (2S,3R)- and (2S,3S)-isomers were in 62% ee. The odor properties of the synthesized four stereoisomers were evaluated by gas chromatography - olfactometry (GC-O), which revealed perceptible di fferences among stereoisomers both in odor features and in intensities.
- Dai, Yifeng,Shao, Junqiang,Yang, Shaoxiang,Sun, Baoguo,Liu, Yongguo,Ning, Ting,Tian, Hongyu
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p. 464 - 468
(2015/01/30)
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- Preparation and odour of cis- and trans-2-methyltetrahydrofuran-3-thiol acetates
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The preparation of cis- and trans-2-methyltetrahydrofuran-3-thiol acetates from (E)-3-penten-1-ol is reported. The mesylate of (E)-3-penten-1-ol was converted into trans- or cis-2-methyl-3-hydroxytetrahydrofuran by oxidation with H2O2 and HCOOH or with KMnO4. cis- or trans-2-Methyltetrahydrofuran-3-thiol acetate was prepared by mesylation and an SN2 nucleophilic substitution with AcSH from trans- or cis-2-methyl-3-hydroxytetrahydrofuran respectively. The configuration of the products was confirmed by their synthesis. Olfactory evaluation of cis- and trans-2-methyltetrahydrofuran-3-thiol acetates indicated some differences both in odour feature and intensity.
- Dai, Yifeng,Sun, Baoguo,Yang, Shaoxiang,Liu, Yongguo,Tian, Hongyu,Shao, Junqiang
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p. 236 - 239
(2014/05/06)
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- The Development of Cyclic Sulfolanes as Novel and High-Affinity P2 Ligands for HIV-1 Protease Inhibitors
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Design and synthesis of a novel series of protease inhibitors incorporating conformationally constrained cyclic ligands for the S2-substrate binding site of HIV-1 protease is described. We recently reported urethanes of 3-tetrahydrofuranyl as P2 ligands for HIV-1 protease inhibitors. Subsequently, we have found that the urethane of 3(S)-hydroxysulfolane further increased the in vitro potency of these inhibitors. Furthermore, introduction of a small 2-alkyl group cis to the 3-hydroxyl group of either heterocyclic system further enhanced enzyme affinity. The cis-2-isopropyl group thus far offered optimum enhancement of the inhibitory properties. This led to the discovery of inhibitor 43 (IC50 3.5 nM, CIC95 50+/-14 nM) of comparable in vitro antiviral potency to the current clinical candidate 1 (Ro 31-8959) but of reduced molecular weight due to the exclusion of the P3 quinoline ligand. Also, it has been demonstrated that the octahydropyrindene derivative 34 is an effective replacement of the P1' decahydroisoquinoline derivative.
- Ghosh, Arun K.,Lee, Hee Yoon,Thompson, Wayne J.,Culberson, Chris,Holloway, M. Katharine,et al.
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p. 1177 - 1188
(2007/10/02)
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- Stereocontrolled Formation of Functionalized erythro-1,2-Diols via Hydroboration of 2-Alkyl-4,5-dihydrofurans
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trans-2-Alkyl-3-hydroxytetrahydrofurans, prepared by the stereospecific hydroboration / oxidation reaction of 2-alkyl-4,5-dihydrofurans, were regioselectively cleaved with (CH3)3SiCl/NaI to afford 1-iodo-erythro-3,4-diols in CH3CN or the corresponding acetonide derivatives in CH3COCH3.
- Amouroux, Roger,Slassi, Abdelmalik,Saluzzo, Christine
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p. 1965 - 1970
(2007/10/02)
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- TRANSPOSITION DES OXIRANNES-ETHANOLS PAR L'INTERMEDIAIRE D'ALCOXYETAINS
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Oxiraneethoxytributyltins prepared from the corresponding oxiraneethanols, on heating at 200 deg C gave, after demetalation with isophthalic acid, 2-oxetanemethanols and/or 3-oxolanols.As appears from about thirty rearrangements the choice between oxetane and oxolane formation is dependent on: (1) the relative degree of substitution of the oxirane ring; cyclization occuring predominantly at the more substituted carbon; and (2) the configuration of the oxirane ring, when both its ends are equally substituted; cis form being more suitable for genaration of the smaller ring.The reaction is shown to proceed with inversion of configuration at the site of oxygen attack.The results of attempts to perform the rearrangement in dilute-phase or throught alkaline metal alkoxides in various media support the conclusion that there is a large contribution by electrophilic assistance to the oxirane ring opening.Such assistance can be efficiently provided by a tin atom in a push-pull mechanism which accomodates all the facts.The present method of oxiraneethanol rearrangement may offer a convenient route to functional oxetanes.
- Bats, J. -P.,Moulines, J.,Picard, P.,Leclercq, D.
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p. 2139 - 2146
(2007/10/02)
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- TRANSPOSITION DES OXIRANNES-ETHANOLS PAR L'INTERMEDIAIRE D'ALCOXYETAINS. INFLUENCE DE LA CONFIGURATION DE L'OXIRANNE
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The transposition of oxirane-ethanols, through alkoxytin compounds, into oxetane-2-methanols and/or oxolan-3-ols (tetrahydrofuran-3-ols) is dependent upon the oxirane configuration.Cis configuration is more suitable for the formation of the smallest ring.Steric hindrance is not sufficient enough to explain the results.
- Bats, J.-P.,Moulines, J.,Picard, P.,Leclerq, D.
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p. 3051 - 3054
(2007/10/02)
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