- The Synthesis and Structure of a Cyclobutane Analogue of Glutamic Acid with an Acetic Acid Side Chain
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A synthetic route involving a hydantoin derivative of bicyclohept-2-ene has been investigated for the preparation of neurotransmitter analogues containing an additional acetic acid substituent on the cyclobutane ring of the potent NMDA receptor agonist trans-1-aminocyclobutane-1,3-dicarboxylic acid.X-Ray analysis showed that the major cyclobutane amino acid produced had the 2-acetic acid and 3-carboxylic acid substituents in the trans-orientation as a result of epimerization during hydantoin hydrolysis.
- Allan, Robin D.,Apostopoulos, Christine,Hambley, Trevor W.
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- Specifically Deuteriated Bicyclohepta-2,6-dienes
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An efficient synthetic route from the dichloroketene/cyclopentadiene adduct to bicyclohepta-2,6-diene has been developed and adapted to prepare deuteriated analogues of this diene labeled specifically at C1-C5, C6, or C7, or any combination of these possibilities.
- Baldwin, John E.,Belfield, Kevin D.
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- An efficient procedure for synthesis of 2-formylcyclopent-2-enecarboxylic acid
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Abstract A synthetic method for 2-formylcyclopent-2-enecarboxylic acid is described. This procedure comprises two steps. The first step is a [2 + 2] cycloaddition reaction, and the second step is a hydrolysis and ring-opening reaction. A plausible mechanism of the hydrolysis and ring-opening reaction was supposed. Then, the effects of different solvents, base mol ratio, concentration of base, and reaction temperature on the yield of the second step were studied. Finally, under the obtained optimized conditions, the product was achieved and isolated in 59.4 % yield, which was more than double the ones reported previously. An improved and efficient procedure for the synthesis of 2-formylcyclopent-2-enecarboxylic acid has been developed.
- Xu, Chaohang,Li, Wei,Jin, Xiaodong,He, Guangke,Zhu, Hongjun
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- Preparation method corey lactone diol
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The invention provides a preparation method of corey lactone diol, which has the advantages of easily available raw materials. The method has the characteristics of mild reaction conditions, simple operation, simple synthetic route, high chemical yield, low cost and the like, and is suitable for industrial production.
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Paragraph 0050-0053
(2021/10/11)
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- A synthesis method of the branch stands lactone diol
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The invention discloses a method for the branch stands lactone diol (( -) - Corey lactone diol) synthetic method, synthesis method of the invention is to dicyclopentadiene as raw materials, by depolymerization, cyclization, oxidation, dechlorination, open-loop, split, Prins reaction, hydrolysis reaction to obtain the target product. The invention discloses a synthetic route, raw material economic, high separation efficiency, and is suitable for industrial production.
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- Access to a Key Building Block for the Prostaglandin Family via Stereocontrolled Organocatalytic Baeyer–Villiger Oxidation
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A new protocol for the construction of a crucial bicyclic lactone of prostaglandins using a stereocontrolled organocatalytic Baeyer–Villiger (B-V) oxidation was developed. The key B-V oxidation of a racemic cyclobutanone derivative with aqueous hydrogen peroxide has enabled an early-stage construction of a bicyclic lactone skeleton in high enantiomeric excess (up to 95 %). The generated bicyclic lactone is fully primed with two desired stereocenters and enabled the synthesis of the entire family of prostaglandins according to Corey′s route. Furthermore, the reactivity and enantioselectivity of B-V oxidation of racemic bicyclic cyclobutanones were evaluated and 90–99 % ee was obtained, representing one of the most efficient routes to chiral lactones. This study further facilitates the synthesis of prostaglandins and chiral lactone-containing natural products to promote drug discovery.
- Zhu, Kejie,Hu, Sha,Liu, Minjie,Peng, Haihui,Chen, Fen-Er
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supporting information
p. 9923 - 9927
(2019/05/16)
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- Synthesis, structure-activity relationships, and mechanistic studies of 5-arylazo-tropolone derivatives as novel xanthine oxidase (XO) inhibitors
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Xanthine oxidase (XO) is an enzyme that contains molybdenum at the active site and catalyzes the oxidation of purine bases to uric acid. Even though XO inhibitors are widely used for the treatment of hyperuricemia and gout, only very few such compounds are clinically used as drugs for the treatment of these diseases. Given the unique physicochemical properties of tropolone, i.e., its chelating effect and the pKa value that is similar to that of carboxylic acid, we have synthesized 22 5-arylazotropolone derivatives as potential XO inhibitors. In vitro enzyme-inhibitory assays for XO revealed that 3-nitro derivative 1j showed the most potent XO inhibitory activity, which is by one order of magnitude more potent than allopurinol. An enzyme-kinetic study revealed that 1j inhibited the production of uric acid by XO both competitively and non-competitively. A docking-simulation study of 1j with XO suggested that the carbonyl and hydroxyl groups of the tropolone ring interact with the hydroxy group that acts as a ligand for molybdenum and the amino acid residues around the active site of XO.
- Sato, Daisuke,Kisen, Takuya,Kumagai, Mina,Ohta, Kiminori
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p. 536 - 542
(2017/12/29)
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- Preparation method of Corey lactone diol
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The invention provides a preparation method of Corey lactone diol, and relates to the technical field of alcohol synthesis. The preparation method comprises the following steps: de-polymerization, cyclization, de-chlorination, splitting, oxidation, Prins reaction, and hydrolysis. The preparation method is simple, is easy to operate, and is beneficial for the industrial production.
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Paragraph 0032
(2018/03/26)
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- Features of catalyzed hydration of 2-(dichloromethyl)-N-[(1R)-1- phenylethyl)]cyclopent-3-ene-1-carboxamides
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The hydration of gem-dichloromethyl group in 2-(dichloromethyl)-N-[(1R)-1- phenylethyl)]cyclopent-3-ene-1-carboxamides in aqueous acetonitrile catalyzed by AgNO3, FeCl3?6H2O, PdCl2, and BaO was investigated. The optimum results were obtained at the use of BaO. It was demonstrated, that Pd-catalyzed reactions initiated intermolecular ether formation from the primary hydration products, bicyclic amides.
- Gizametdinov,Miftakhov
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experimental part
p. 694 - 697
(2009/12/05)
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- Simple synthetic protocol for the preparation of enantiomeric 3-oxabicyclo[3.3.0]oct-6-en-2-ones
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Diastereomeric amides produced via the decomposition of easily available (±)-7,7-dichlorobicyclo[3.2.0]hept-2-en-6-one by treatment with (+)- or (-)-α-methylbenzylamines were transformed into bicyclic lactam-aminals, which can easily be separated using the column chromatography on SiO2. The latter products lead to enantiomeric 3-oxabicyclo[3.3.0]oct-6-en-2-ones after the removal of the chiral auxiliary. Crown Copyright
- Gimazetdinov, Airat M.,Vostrikov, Nikolay S.,Miftakhov, Mansur S.
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p. 1094 - 1099
(2008/09/20)
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- A practical route to both enantiomers of bicyclo[3.3.0]oct-2-en-7-one and their use for the synthesis of key trisubstituted cyclopentanes
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We describe new methodology for the synthesis of both enantiomers of 7,7-dichlorobicyclo[3.2.0]hep-2-en-6-one and conversion of these compounds into stereochemically defined bicyclo[3.3.0]oct-2-en-7-ones and thence trisubstituted cyclopentanes. These are key intermediates for the synthesis of prostanoids, brefeldin and other cyclopentane-containing natural products.
- Cousin, David,Mann, John
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p. 3534 - 3540
(2008/09/21)
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- Syntheses of novel 1,3-diazaazulene derivatives and their nonlinear optical characterization
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We have synthesized three new 1,3-diazaazulene derivatives, namely, 2-(4′-N,N-dimethylaminophenyl)-6-nitro-1,3-diazaazulene (18, DMAPNA), 2-(4′-aminophenyl)-6-nitro-1,3-diazaazulene (19, APNA) and 2-[4′-N-(2-hydroxyethyl)aminophenyl]-6-nitro-1,3-diazaazulene (20, HEAPNA), each of them contains an amino substitute as the electron donor (D), 2-phenyl-1,3-diazaazulene as the π-conjugated bridge and a nitro as the electron acceptor (A). Our theoretical results have predicted that these D-π-A type chromophores possess low ground-state dipole moment (μg) and large first-order hyperpolarizability (β), which may facilitate a low degree of aggregation for the chromophores dispersed in a polymeric matrix as well as a large nonlinear optical (NLO) response. The expected NLO performance has been confirmed by the experimental β and μg values, e.g., for 18, 407.8 × 10-30 esu and 4.7 D, respectively. The origins of large β and low μg are explained in terms of a two-state quantum model. The DMAPNA (18)-doped and poled polymethylmethacrylate film exhibits a large second harmonic generation (SHG) coefficient of d33 = 10.9 pm V-1 with excellent thermal stability (above 70% of the maximal SHG coefficient remains at ~100 °C). The Royal Society of Chemistry.
- Zhu, Yun-Ji,Qin, An-Jun,Fu, Li-Min,Ai, Xi-Cheng,Guo, Zhi-Xin,Zhang, Jian-Ping,Ye, Cheng
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p. 2101 - 2106
(2008/02/07)
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- Dynamic effects on the periselectivity, rate, isotope effects, and mechanism of cycloadditions of ketenes with cyclopentadiene
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The cycloadditions of cyclopentadiene with diphenylketene and dichloroketene are studied by a combination of kinetic and product studies, kinetic isotope effects, standard theoretical calculations, and trajectory calculations. In contrast to recent reports, the reaction of cyclopentadiene with diphenylketene affords both [4 + 2] and [2 + 2] cycloadducts directly. This is surprising, since there is only one low-energy transition structure for adduct formation in mPW1K calculations, but quasiclassical trajectories started from this single transition structure afford both [4 + 2] and [2 + 2] products. The dichloroketene reaction is finely balanced between [4 + 2] and [2 + 2] cycloaddition modes in mPW1 K calculations, as the minimum-energy path (MEP) leads to different products depending on the basis set. The MEP is misleading in predicting a single product, as trajectory studies for the dichloroketene reaction predict that both [4 + 2] and [2 + 2] products should be formed. The periselectivity does not reflect transition state orbital interactions. The 13C isotope effects for the dichloroketene reaction are well-predicted from the mPW1K/6-31+G** transition structure. However, the isotope effects for the diphenylketene reaction are not predictable from the cycloaddition transition structure and transition state theory. The isotope effects also appear inconsistent with kinetic observations, but the trajectory studies evince that nonstatistical recrossing can reconcile the apparently contradictory observations. B3LYP calculations predict a shallow intermediate on the energy surface, but trajectory studies suggest that the differing B3LYP and mPW1K surfaces do not result in qualitatively differing mechanisms. Overall, an understanding of the products, rates, selectivities, isotope effects, and mechanism in these reactions requires the explicit consideration of dynamic trajectories.
- Ussing, Bryson R.,Hang, Chao,Singleton, Daniel A.
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p. 7594 - 7607
(2007/10/03)
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- Syntheses and biological evaluation of vinblastine congeners.
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Sixty-two congeners of vinblastine (VLB), primarily with modifications of the piperidine ring in the carbomethoxycleavamine moiety of the binary alkaloid, were synthesized and evaluated for cytotoxicity against murine L1210 leukemia and RCC-2 rat colon cancer cells, and for their ability to inhibit polymerization of microtubular protein at 10(7) M concentrations was found for L1210 inhibition by these compounds, with the most active 1000x as potent as vinblastine.
- Kuehne, Martin E,Bornmann, William G,Marko, Istvan,Qin, Yong,LeBoulluec, Karen L,Frasier, Deborah A,Xu, Feng,Mulamba, Tshilundu,Ensinger, Carol L,Borman, Linda S,Huot, Anne E,Exon, Christopher,Bizzarro, Fred T,Cheung, Julia B,Bane, Susan L
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p. 2120 - 2136
(2007/10/03)
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- Identification of novel mammalian squalene synthase inhibitors using a three-dimensional pharmacophore
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Squalene synthase (E.C. 2.5.1.21) catalyses the reductive dimerisation of farnesyl diphosphate in a [1-4] head to head fashion to form squalene, and is the first committed step in cholesterol biosynthesis. Specific inhibitors of squalene synthase would inhibit cholesterol formation and allow production of other important compounds derived from the cholesterol biosynthetic pathway, namely the ubiquinones (co-enzyme Q10), dolichol, and would also allow the isoprenylation process of ras by farnesyl-protein transferase. The construction of a hypothetical squalene synthase three-dimensional pharmacophore is presented. It serves as a template for the identification of several new potential classes of inhibitors. The synthesis, anti-microbial and mammalian pig liver squalene synthase activities of analogues based on the bicyclo[3.2.0]heptane and bicyclo[3.3.0]octane ring systems are reported. Analogues of the latter system are pro-drug type inhibitors and exhibit promising biological activity.
- Fairlamb, Ian J.S.,Dickinson, Julia M.,O'Connor, Rachael,Higson, Seamus,Grieveson, Lynsey,Marin, Veronica
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p. 2641 - 2656
(2007/10/03)
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- Fungicidal activity of β-thujaplicin analogues
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The fungicidal activity of analogues of β-thujaplicin, a natural product responsible for the durability of heartwood of several cupressaceous trees, was investigated in vitro on the growth of different white and brown rot fungi involved in wood biodegradation, Coriolus versicolor, Phanerochaete chrysosporium, Poria placenta and Gloephyllum trabeum. The study shows that 2-hydroxycyclohepta-2,4,6-trienone (tropolone), easily prepared according to a literature procedure, possesses interesting fungicidal activity when compared to β-thujaplicin, azaconazole, tebuconazole and copper oxine, which suggests this compound should be examined further as a potential biocide for wood preservation.
- Baya, Mounir,Soulounganga, Patrice,Gelhaye, Eric,Grardin, Philippe
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p. 833 - 838
(2007/10/03)
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- Thermal rearrangement of 7-methylbicyclo[3.2.0]hept-2-ene: An experimental probe of the extent of orbital symmetry control in the [1,3] sigmatropic rearrangement
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The gas-phase thermal rearrangement of exo-7-methylbicyclo[3.2.0]hept-2-ene yields almost exclusively 5-methylnorbornene products. Inversion (i) of configuration dominates this [1,3] sigmatropic shift although some retention (r) is also observed. Because the [1,3] migration can only occur suprafacially (s) in this geometrically constrained system, the si/sr ratio of 7 observed for the migration of C7 in exo-7-methylbicyclo[3.2.0]hept-2-ene indicates that the orbital symmetry rules are somewhat permissive for the [1,3] sigmatropic migration of carbon.
- Bender, Jared D.,Leber, Phyllis A.,Lirio, Ruel R.,Smith, Randall S.
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p. 5396 - 5402
(2007/10/03)
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- New proline mimetics: Synthesis of thrombin inhibitors incorporating cyclopentane- and cyclopentenedicarboxylic acid templates in the P2 position. Binding conformation investigated by X-ray crystallography
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With the aim to prepare nonpeptidic thrombin inhibitors, the amino acids of the thrombin-inhibiting tripeptide chain D-Phe-Pro-Arg were replaced with isosteres. Arg was replaced with the more rigid P1 truncated p- amidinobenzylamine (Pab), Pro with either cyclopentane-1,2-dicarboxylic acid or cyclopentene-1,5-dicarboxylic acid, and D-Phe with a series of readily available lipophilic amines. One of the most potent compounds (25, pIC50 = 6.01) in these series was cocrystallized with thrombin where the X-ray crystal structure provide insight to the structure-activity relationship (SAR).
- N?teberg, Daniel,Br?nalt, Jonas,Kvarnstr?m, Ingemar,Linschoten, Marcel,Musil, Djordje,Nystr?m, Jan-Erik,Zuccarello, Guido,Samuelsson, Bertil
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p. 1705 - 1713
(2007/10/03)
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- Free radical-based annulation of alkenes yielding fused cycloheptanones
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Stereospecific annulation of cyclic alkenes for the preparation of cis-fused seven-membered ring systems was accomplished by sequential [2+2] cycloaddition, exo-allylation, hydrohalogenation, and free radical ring expansion. The new strategy extends our recently developed cyclobutanone-based ring expansion reactions.
- Zhang, Wei,Hua, Ye,Hoge, Garrett,Dowd, Paul
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p. 3865 - 3868
(2007/10/02)
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- PROSTANOIDS. LII. (+/-)-7,7-DICHLORO-4β-TRIMETHYLSILYLBICYCLOHEPT-3-EN-6-ONE IN THE SYNTHESIS OF PROSTANOIDS. RACEMIC CARBACYCLIN
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The products from the Prins reaction of formaldehyde and (+/-)-7,7-dichloro-4β-trimethylsilylbicyclohept-3-en-6-one were isolated and characterized.The optimum conditions were found for the production of the isomeric 2β-acetoxy-6,6(7,7)-dichlorobicyclohept-3-en-7(6)-ones and 2β-acetoxymethyl-3α-acetoxy-6,6(7,7)-dichlorobicyclohept-3-en-7(6)-ones and also (1R,2S,5R,6S,10R)-3,3-dichloro-4-oxo-10-hydroxy(acetoxy)-8-oxatricyclo2,5>undecanes, suitable for the subsequent synthesis of modified prostanoids.An effective scheme for the synthesis of (+/-)-carbacyclin was worked out on the basis of the monoacetates of a series of bicycloheptenones through the corresponding 2β-acetoxymethyl-3α-acetoxybicyclooctan-7-ones.
- Tolstikov, G. A.,Akhmetvaleev, R. R.,Zhurba, V. M.,Vasil'eva, M. S.,Miftakhov, M. S.
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p. 543 - 552
(2007/10/02)
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- The Reaction between Bis(trimethylsilyl)cyclopentadiene and Dichloroketen, and the Diels-Alder Reactions between N-Phenylmaleimide and Two Silylated Methylcyclopentadienes
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Bis(trimethylsilyl)cyclopentadiene reacts with dichloroketen to give only the adduct (7) derived from the 2,5-disilylated isomer (5).Methyl(trimethylsilyl)cyclopentadiene (18) and trimethylsilylmethylcyclopentadiene (21) give Diels-Alder adducts (19) and (20) and (22) and (23) in which the regioselectivity is unaffected by the presence of the silyl group.Epoxidation of the edduct (22) and acid-catalysed opening of the epoxide lead to formation of the exo-methylenenorbornane (26) in a rearrangement controlled by the presence of the silyl group.
- Fleming, Ian,Williams, Richard Vaughan
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p. 684 - 688
(2007/10/02)
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- Acetolysis of Some Bicyclo-2-octenyl Tosylates
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The products of the acetolysis of the stereoisomeric 6-, 7-, and 8-bicyclo-2-octenyl tosylates are reported.These tosylates were themselves stable to skeletal rearrangements but were found to undergo 1,2 hydride shifts and elimination solvolysis.
- Nee, Michael,Roberts, John D.
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