- Design and synthesis of pinane oxime derivatives as novel anti-influenza agents
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Parasitic characteristics, mutations and resistance of influenza A virus make it difficult for current influenza antiviral drugs to maintain long-term effectiveness. Currently, to design non-adamantane compounds targeting the S31N mutant of M2 proton channel is a promising direction for the development of novel anti-influenza drugs. In our previous research, a pinanamine-based antiviral M090 was discovered to target hemagglutinin instead of M2, with its structure being highly similar to reported M2-S31N inhibitors. Herein, a series of pinane oxime derivatives were designed from scratch and evaluated for anti-influenza activity and their cytotoxicity in vitro. Utilizing a combination of structure-activity relationship analysis, electrophysiological assay and molecular docking, the most potent compound 11h, as a M2-S31N blocker, exhibited excellent activity with EC50 value at the low micromolar level against both H3N2 and H1N1. No significant toxicity of 11h was observed. In addition, compound 11h was located tightly in the pore of the drug-binding site with the thiophene moiety facing down toward the C-terminus, and did not adopt a similar position and orientation as the reference inhibitor.
- Dong, Jianghong,Xiao, Mengjie,Ma, Qinge,Zhang, Guicheng,Zhao, Weijie,Kong, Mengjie,Zhang, Yue,Qiu, Luyun,Hu, Wenhui
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Read Online
- Asymmetric Synthesis of Oxygenated Monoterpenoids of Importance for Bark Beetle Ecology
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Herein we report the asymmetric syntheses of a number of oxygenated terpenoids that are of importance in the chemical ecology of bark beetles. These are pinocamphones, isopinocamphones, pinocarvones, and 4-thujanols (= sabinene hydrates). The camphones were synthesized from isopinocampheol, the pinocarvones from β-pinene, and the thujanols from sabinene. The NMR spectroscopic data, specific rotations, and elution orders of their stereoisomers on a chiral GC-phase (β-cyclodextrin) are also reported. This enables facile synthesis of pure compounds for biological activity studies and identification of stereoisomers in mixed natural samples.
- Ganji, Suresh,Svensson, Fredric G.,Unelius, C. Rikard
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p. 3332 - 3337
(2020/11/30)
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- Chiral terpene auxiliaries V: Synthesis of new chiral γ-hydroxyphosphine oxides derived from α-pinene
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New chiral regioisomeric γ-hydroxyphosphine ligands were synthesized from α-pinene. The key transformation was the thermal [2,3]-sigmatropic rearrangement of allyldiphenylphosphinites, obtained from (1R,2R,4S,5R)-3-methyleneneoisoverbanol and (1R,2R,3R,5R)-4-methyleneneoisopinocampheol, to allylphosphine oxides. Hydroxy groups were introduced stereoselectively through a hydroboration–oxidation reaction proceeding from the less hindered site providing a trans relationship between the hydroxy and the phosphine substituents.
- Kmieciak, Anna,Krzemiński, Marek P.
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supporting information
p. 2493 - 2499
(2019/12/11)
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- Synthesis of bimetallic Zr(Ti)-naphthalendicarboxylate MOFs and their properties as Lewis acid catalysis
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Bimetallic Zr(Ti)-NDC based metal-organic frameworks (MOFs) have been prepared by incorporation of titanium(iv) into zirconium(iv)-NDC-MOFs (UiO family). The resulting materials maintain thermal (up to 500 °C), chemical and structural stability with respect to parent Zr-MOFs as can be deduced from XRD, N2 adsorption, FTIR and thermal analysis. The materials have been studied in Lewis acid catalyzed reactions, such as, domino Meerwein-Ponndorf-Verley (MPV) reduction-etherification of p-methoxybenzaldehyde with butanol, isomerization of α-pinene oxide and cyclization of citronellal.
- Rasero-Almansa, Antonia M.,Iglesias, Marta,Sánchez, Félix
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p. 106790 - 106797
(2016/11/23)
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- Ring-opening of epoxides promoted by organomolybdenum complexes of the type [(η5-C5H4R)Mo(CO)2(η3-C3H5)] and [(η5-C5H5)Mo(CO)3(CH2R)]
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The cyclopentadienyl molybdenum carbonyl complexes [(η5-C5H4R)Mo(CO)2(η3-C3H5)] and [(η5-C5H5)Mo(CO)3(CH2R)] (R = H, COOH) have been shown to promote acid-catalysed reactions in liquid phase, under moderate conditions. The catalytic alcoholysis of styrene oxide with ethanol at 35 °C gave 2-ethoxy-2-phenylethanol in 100% yield within 30 min for the dicarbonyl complexes and 3-6 h for the tricarbonyl complexes. Steady catalytic performances were observed in consecutive runs with the same catalytic solution, suggesting fairly good catalytic stability. In the second acid-catalysed reaction studied, the isomerization of α-pinene oxide at 55 °C gave campholenic aldehyde and trans-carveol in a total yield of up to 86% at 100% conversion. Chemoselectivity is shown to be solvent dependent.
- Bruno, Sofia M.,Gomes, Ana C.,Abrantes, Marta,Valente, Anabela A.,Pillinger, Martyn,Gon?alves, Isabel S.
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p. 179 - 183
(2015/10/19)
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- Catalytic isomerisation of α-pinene oxide in the presence of ETS-10 supported ferrocenium ions
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Ferrocenium ions, [Fc]+, have been immobilised in the microporous titanosilicate ETS-10 by ion exchange of Na+/K+ ions under hydrothermal conditions. The resultant hybrid inorganic-organometallic (ETS-10/[Fc]+) material was characterised by elemental analysis, diffuse reflectance UV-Vis spectroscopy, FT-IR spectroscopy, powder X-ray diffraction, scanning electron microscopy, and thermogravimetric analysis. The ETS-10/[Fc]+ sample was tested as a catalyst for the isomerisation of α-pinene oxide (PinOx) at 35 C. With α, α, α-trifluorotoluene (TFT) as solvent, campholenic aldehyde (CPA) was the main product formed in 38% yield at 100% conversion and 30 min reaction. Other reaction products included trans-carveol, iso-pinocamphone and trans-pinocarveol. The same PinOx conversion and CPA yield could be reached within 1 min reaction time by increasing the reaction temperature (to 55 °C) and the Fe:PinOx molar ratio. Other solvents (hexane, CH3CN, toluene) led to poorer results than TFT. Characterisation of the used catalyst, together with an analysis of the catalytic activity of the liquid phase obtained after contact of ETS-10/[Fc]+ with TFT, indicated that the ETS-10/[Fc]+ sample was resistant toward leaching of iron-containing active species. When the recovered solid was reused in a second batch run, catalytic activity was lower than in the first run, while selectivity to CPA was higher.
- Bruno, Sofia M.,Gomes, Ana C.,Coelho, Ana C.,Brand?o, Paula,Valente, Anabela A.,Pillinger, Martyn,Gon?alves, Isabel S.
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- Identification of camphor derivatives as novel M2 ion channel inhibitors of influenza A virus
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Amantadine derivatives have been the only drugs marketed as M2 inhibitors of influenza A for decades. The identification of pinanamine as a novel M2 inhibitor suggests that M2 ion channels can accommodate more types of hydrophobic scaffolds. Herein, we further investigated the M2 ion channels and identified camphor derivatives as new types of M2 inhibitors. Compound 18 was found to be more potent than amantadine against wild-type influenza virus. The molecular docking revealed that compound 18 occupies more space in the M2 ion channel than amantadine and thus exhibits enhanced activity. This journal is
- Zhao, Xin,Zhang, Zhen-Wei,Cui, Wei,Chen, Shengwei,Zhou, Yang,Dong, Jianghong,Jie, Yanling,Wan, Junting,Xu, Yong,Hu, Wenhui
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supporting information
p. 727 - 731
(2015/04/27)
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- Several monoterpenoid bromination products
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2α-Bromo,10β-pinanone-3 and 3α-bromo,10β-pinanone-4 were formed with 92-98% selectivity by bromination of isopinocamphone and cis-verbanone with Meldrum's acid dibromide. 3α-Bromo, 10β-pinanone-4 was prepared for the first time. Its structure was confirmed by an XSA. Bromination of menthone by Meldrum's acid dibromide formed mainly a mixture of diastereomeric 2-bromomenthones in a 2:1 ratio. Oxidative bromination of isopinocampheol by Ce(III)-LiBr-H2O2 caused rearrangement of the pinane structure into bornane and formed a mixture of 6-endo- and 6-exo-bromocamphor in a 5:1 ratio.
- Frolova,Bezuglaya,Alekseev,Slepukhin,Kuchin
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p. 449 - 454
(2014/08/18)
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- ANALGESIC COMPOUNDS, METHODS, AND FORMULATIONS
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Provided are analgesic compounds, and salts thereof, of formula: (I) wherein A is: (A) Additionally, pharmaceutical formulations and methods of use employing the above compounds are provided.
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Paragraph 0115-0116
(2013/09/12)
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- ANALGESIC COMPOUNDS, METHODS, AND FORMULATIONS
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Provided are compounds, and salts thereof, of formula (I): wherein (A) is R1 is hydrogen, C1-C5 alkyl, C1-C5 alkoxy, C1-C5 haloalkyl, C1-C5 alkanol, -(C1-C5 alkyl)phenyl, or phenyl, or a group of the formula -C(O)-R12, where R12 may be C1-C5 alkyl, C1-C5 alkoxy, C1-C5 haloalkyl, C1-C5 alkanol, -(C1-C5 alkyl)phenyl, or phenyl; R2 and R3 are independently hydrogen, C1-C5 alkyl, C1-C5 alkoxy, halogen, C1-C5 haloalkyl, or C1-C5 haloalkoxy; R4 and R5 are independently hydrogen, C1-C5 alkyl, or -(C1-C5 alkyl)phenyl; R6 is hydrogen, hydroxy, or is absent; R7 is hydrogen; R8 and R9 are independently hydrogen or methyl; R10 is hydrogen; R11 is hydrogen or C1-C5 alkyl; or R7 and R10 combine to form -CH2- or -(CH2)2-; or R8 and R9 combine to form a cyclopropyl group with the carbon to which they are attached; or R10 and R11 combine to form -CH2- or -(CH2)3-. Additionally, pharmaceutical formulations and methods of use employing the above compounds are provided.
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Page/Page column 76-77
(2012/08/08)
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- ANALGESIC COMPOUNDS, METHODS, AND FORMULATIONS
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Provided are analgesic compounds, and salts thereof, of formula: ( I ) wherein A is: ( A ) Additionally, pharmaceutical formulations and methods of use employing the above compounds are provided.
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Page/Page column 76-77
(2012/08/08)
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- Incorporation of an allene unit into α-pinene via β- elimination
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The two double-bond isomers 3-iodo-2,6,6-trimethylbicyclo[3.1.1]hept-2-ene (6b) and 3-iodo-4,6,6-trimethylbicyclo[3.1.1]hept-2-ene (11) were synthesized by reacting 2,6,6-trimethylbicyclo[3.1.1]heptan-3-one (9) with hydrazine, followed by treatment with I2 in the presence of Et3N. Treatment of 11 with t-BuOK as base in diglyme at 220 resulted in the formation of 9 and 6,6-dimethyl-4-methylidenebicyclo[3.1.1]hept-2-ene (12). For the formation of 9, the cyclic allene 7 is proposed as an intermediate. Treatment of the second isomer, 6b, with t-BuOK at 170 gave rise to the diene 12 and the dimerization product 17. The underlying mechanism of this transformation is discussed. On the basis of density-functional-theory (DFT) calculations on the allene 7 and the alkyne 15, the formation of the latter as the intermediate was excluded. Verlag Helvetica Chimica Acta AG.
- Kilbas, Benan,Azizoglu, Akin,Balci, Metin
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p. 1449 - 1456
(2007/10/03)
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- Synthetic scope of alcohol transfer dehydrogenation catalyzed by Cu/Al 2O3: A new metallic catalyst with unusual selectivity
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A method for the anaerobic oxidation of a wide series of alcohols including cyclohexanols and steroidal alcohols, has been set up. It relies on a transfer dehydrogenation reaction from the substrate alcohol to styrene catalyzed by a heterogeneous, reusable copper catalyst under very mild liquid phase experimental conditions (90°C, N2) and shows unusual selectivity. Thus, the method is selective for the oxidation of secondary and allylic alcohols even in the presence of unprotected primary and benzylic alcohols. Electronic effects and the choice of the hydrogen acceptor account for the selectivity observed.
- Zaccheria, Federica,Ravasio, Nicoletta,Psaro, Rinaldo,Fusi, Achille
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p. 6426 - 6431
(2008/09/20)
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- Formation of trans-verbenol and verbenone from α-pinene catalysed by immobilised Picea abies cells
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Both enantiomers and the raceinate of α-pinene were transformed by Picea abies cells immobilised on alginate. The main products were cis- and trans-verbenol, the later being further transformed to verbenone. The enantiomeric purity of each product more or less corresponded to that of the substrate. Transformation by free cells was faster than that by the immobilised cells. The ratio of products differed to some extent between the transformation by tree and immobilised cells.
- Vanek, Tomas,Halik, Jan,Vankova, Radmila,Valterova, Irena
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p. 321 - 325
(2007/10/03)
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- Metabolism and mode of action of cis- and trans-3-pinanones (the active ingredients of hyssop oil)
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1. Hyssop oil is an important food additive and herbal medicine and the principal active ingredients are (-)-cis- and (-)-trans-3-pinanones. No information is available on their metabolism or specific mode of action. 2. The metabolites of cis- and trans-3-pinanones were examined from mouse and human liver microsomes and human recombinant P4503A4 with NADPH and on administration to mouse by gas chromatography/chemical ionization mass spectrometry comparison with standards from synthesis. 3. The major metabolite of cis-3-pinanone in each P450 system and in brain of the i.p.-treated mouse in quantitative studies was 2-hydroxy-cis-3-pinanone, and two minor metabolites were hydroxypinanones other than 2-hydroxy-trans-3-pinanone and 4S-hydroxy-cfs-3-pinanone. The urine from oral cis-3-pinanone treatment examined on a qualitative basis contained conjugates of metabolites observed in the microsomal systems plus 2,10-dehydro-3-pinanone. 4. Trans-3-pinanone was metabolized more slowly than the cis-isomer in each system to give hydroxy derivatives different than those derived from cis-3-pinanone. 5. Cis- and trans-3-pinanones and hyssop oil act as γ-aminobutyric acid type A (GABAA) receptor antagonists based on inhibition of 4′-ethynyl-4-n-[2,3-3H2] propylbicycloorthobenzoate ([3H]EBOB) binding in mouse brain membranes (IC50 of 35-64μM) and supported by tonic/clonic convulsions in mouse (i.p. LD50 175 to >250 mg kg-1) alleviated by diazepam. The cis-3-pinanone metabolites 2-hydroxy-cis-3-pinanone and 2,10-dehydro-3-pinanone exhibit reduced toxicity and potency for inhibition of [3H]EBOB binding.
- Hoeld,Sirisoma,Sparks,Casida
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p. 251 - 265
(2007/10/03)
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- New chiral 2,2′:6′,2″-terpyridine ligands from the chiral pool: Synthesis, crystal structure of a rhodium complex and uses in copper- and rhodium-catalyzed enantioselective cyclopropanation of styrene
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A number of chiral C2-symmetric 2,2′:6′,2″ terpyridines L1-L4 were synthesized in moderate to good yields from commercially available chiral materials. Copper(II) and rhodium(III) chloride complexes of these ligands were prepared in good yields. The Rh(L2)Cl3 complex was isolated as a yellow crystalline solid and characterized by X-ray crystallography. Both Cu(L)(OTf)2 and Rh(L)(OTf)3 were found to be active catalysts in the cyclopropanation of styrene with ethyl diazoacetate. Enantioselectivity up to 82% e.e. was observed.
- Kwong, Hoi-Lun,Wong, Wing-Leung,Lee, Wing-Sze,Cheng, Leung-Shi,Wong, Wing-Tak
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p. 2683 - 2694
(2007/10/03)
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- Aminium Salts Catalyzed Rearrangement of α-Pinene and β-Ionone Oxides
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β-ionone and α-pinene oxides 1,3 isomerize rapidly and selectively to 1-(1,2,2-trimethylcyclopent-1-yl)-pent-2-en-1,4-dione 2 and the industrially important 2,2,3-trimethyl-3-cyclopentene acetaldehyde 4, under the influence of catalytic amounts of aminium salts A, B.In order to find insights into the mechanism of our procedure, protic and Lewis acids-catalyzed rearrangements have also been reconsidered.
- Lopez, Luigi,Mele, Giuseppe,Fiandanese, Vito,Cardellicchio, Cosimo,Nacci, Angelo
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p. 9097 - 9106
(2007/10/02)
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- Studies on the Oxidation of cis- and trans-Pinane with Molecular Oxygen
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The pinanes are preferably attacked at the tertiary C-H bond in 2-position, but products of the oxidative attack at the secondary C-H-bonds in 3- and 4-position are also found.At 100 deg C cis-pinane is attacked more easily than trans-pinane (kcis : ktrans = 6.4), the relative rates of attack at the secondary C-H bonds in positions 3 and 4 with respect to the tertiary C-H bond in 2-position were also determined (in cis-pinane ksec : ktert = 0.027; in trans-pinane ksec : ktert = 0.20).After the attack at the 2-C-H bond the radical formed can either react with oxygen to form the corresponding cis- and trans-peroxy radicals and further to give cis- and trans-2-hydroperoxy pinane or fragmentate to the monocyclic radical derived from α-terpinene, giving as a final products α-terpinene hydroperoxide and the bicyclic 8-hydroperoxy 4,4,8-trimethyl 2,3-dioxabicyclononane.The corresponding alcohols were found after reduction with sodium sulphite.The oxidation at position 2 of the pinanes delivers not only the cis- and trans-hydroperoxide but also, as short-lived intermediates, the corresponding 2-pinanyloxy radicals.These radicals fragmentate forming a carbon radical with cyclobutane structure whose oxidation products were identified.Besides fragmentation of the 2-pinanyloxy radical also an intramolecular H-transfer from the methyl group in 9-position to the oxygen of the trans-pinanyloxy radical takes place leading to 9-hydroperoxy trans-pinane-2-ol.
- Brose, Thomas,Pritzkow, Wilhelm,Thomas, Gerda
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p. 403 - 409
(2007/10/02)
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- Enantioselectivity in the Biotransformation of Mono- and Bicyclic Monoterpenoids with the Cultured Cells of Nicotiana tabacum
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The biotransformation of the enantiomeric pairs of p-menthane and bicyclo and heptane derivatives with the cultured cells of Nicotiana tabacum was investigated.It was found that (i) the cultured cells discriminate the enantiomers of p-menthan-2-ol and bicycloheptan-2-ol and bicycloheptan-3-ol derivatives, and enantioselectively convert these alcohols to the corresponding ketones, (ii) the cells reduce the carbonyl group of p-methan-2-one derivatives to a high extent, but not that of p-menthan-3-ones, and (iii) the cells discriminate the enantiomers of bicyclohept-2-en-4-one (verbenone) and enantioselectively reduce the C-C double bond of the (1S,5S)-enantiomer.
- Hamada, Hiroki
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p. 869 - 878
(2007/10/02)
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- Enantioselectivity in the Biotransformation of Bicycloheptanes with the Cultured Cells of Nicotiana tabacum
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The biotransformation of the enantiomeric pairs of bicycloheptane derivatives with the cultured cells of Nicotiana tabacum was investigated.The hydrogenation of the C-C double bond of verbenone took place enantioselectively in preference of the (1S,5S)-enantiomer and the hydrogen attack occurred stereospecifically from the re-face at its C-2.The oxidation of the hydroxyl group of neoisopinocampheol occurred enantioselectively in preference of the (1S,2S,3R,5R)-enantiomer, whereas such an enantioselective oxidation was not the case for neoisoverbanol.
- Suga, Takayuki,Hamada, Hiroki,Hirata, Toshifumi
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p. 471 - 474
(2007/10/02)
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- SYNTHESIS AND STEREOCHEMISTRY OF SECONDARY AMINES OF THE 2,6,6-TRIMETHYLBICYCLOHEPTANE SERIES
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1S,2S,3R-N-Alkyl-2,6,6-trimethylbicyclohept-3-ylamines were synthesized by the catalytic hydroamination of 1R,2R,3R-pinan-3-ol (isopinocampheol) with aliphatic nitriles.The absolute configuration of the obtained compounds was determined.The reaction takes place strictly stereospecifically through the epimarization of 1R,2R-pinan-3-one to 1S,2S-pinan-3-one.
- Kalechits, G. V.,Kozlov, N. G.,Vyalimyae, T. K.
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p. 2097 - 2101
(2007/10/02)
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- ORGANOBORANES FOR SYNTHESIS. 3. OXIDATION OF ORGANOBORANES WITH AQUEOUS CHROMIC ACID. A CONVENIENT SYNTHESIS OF KETONES FROM ALKENES VIA HYDROBORATION
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Organoboranes react with alkaline hydrogen peroxide to provide a wide variety of alcohols.These alcohols can be taken up in ether solvent and converted without isolation into the corresponding ketones by treatment with chromic acid.Organoboranes can also be oxidized directly with chromic acid to the corresponding ketones.The chromic acid oxidation of organoboranes provides a new, convenient procedure for the synthesis of α-substituted cycloalkanones via hydroboration.The conversion of organoboranes into ketones proceeds through the intermediate alcohol.Representative cycloalkanones and α-methylcycloalkanones have been prepared from the corresponding alkenes via hydroboration, followed by chromic acid oxidation.
- Brown, Herbert C.,Garg, Chandra P.
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p. 5511 - 5514
(2007/10/02)
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