- High-Throughput Synthesis of (S)-α-Phellandrene through Three-Step Sequential Continuous-Flow Reactions
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The combination of continuous-flow processing with heterogeneous catalysts allows for efficient, sustainable, multistep synthesis. Here, we report the continuous-flow synthesis of a valuable terpene product, phellandrene, from a readily available natural feedstock. The protocol consists of selective hydrogenation using a highly active and stable supported platinum catalyst, dehydrative hydrazone formation, followed by the Shapiro reaction. Appropriate design of the reactor allowed for high productivity and space-time yield. Phellandrene was synthesized on a 30-g scale over 6 h, giving high yields, purity, and productivity.
- Miller, Samuel J.,Ishitani, Haruro,Furiya, Yuichi,Kobayashi, Shū
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supporting information
p. 192 - 198
(2021/02/05)
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- Transition metal triflate catalyzed conversion of alcohols, ethers and esters to olefins
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Herein, we report an efficient transition metal triflate catalyzed approach to convert biomass-based compounds, such as monoterpene alcohols, sugar alcohols, octyl acetate and tea tree oil, to their corresponding olefins in high yields. The reaction proceeds through C-O bond cleavage under solvent-free conditions, where the catalytic activity is determined by the oxophilicity and the Lewis acidity of the metal catalyst. In addition, we demonstrate how the oxygen containing functionality affects the formation of the olefins. Furthermore, the robustness of the used metal triflate catalysts, Fe(OTf)3 and Hf(OTf)4, is highlighted by their ability to convert an over 2400-fold excess of 2-octanol to octenes in high isolated yields.
- Keskiv?li,Parviainen,Lagerblom,Repo
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p. 15111 - 15118
(2018/05/04)
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- Converting S-limonene synthase to pinene or phellandrene synthases reveals the plasticity of the active site
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S-limonene synthase is a model monoterpene synthase that cyclizes geranyl pyrophosphate (GPP) to form S-limonene. It is a relatively specific enzyme as the majority of its products are composed of limonene. In this study, we converted it to pinene or phellandrene synthases after introducing N345A/L423A/S454A or N345I mutations. Further studies on N345 suggest the polarity of this residue plays a critical role in limonene production by stabilizing the terpinyl cation intermediate. If it is mutated to a non-polar residue, further cyclization or hydride shifts occurs so the carbocation migrates towards the pyrophosphate, leading to the production of pinene or phellandrene. On the other hand, mutant enzymes that still possess a polar residue at this position produce limonene as the major product. N345 is not the only polar residue that may stabilize the terpinyl cation because it is not strictly conserved among limonene synthases across species and there are also several other polar residues in this area. These residues could form a “polar pocket” that may collectively play this stabilizing role. Our study provides important insights into the catalytic mechanism of limonene synthases. Furthermore, it also has wider implications on the evolution of terpene synthases.
- Xu, Jinkun,Ai, Ying,Wang, Jianhui,Xu, Jingwei,Zhang, Yongkang,Yang, Dong
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- Mechanisms into dehydroaromatization of bio-derived limonene to: P -cymene over Pd/HZSM-5 in the presence and absence of H2
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The mechanisms of dehydroaromatization of limonene to p-cymene are intrinsically investigated over Pd/HZSM-5 under different N2/H2 atmospheres using the mathematical tool of Matlab. It is found that the dehydroaromatization reaction network starts with the isomerization step, and is followed by the sequential dehydrogenation in the presence of N2 or H2 at the selected system. The addition of hydrogen in the atmosphere would not change this reaction pathway, but leads to lower selectivity of p-cymene due to the accelerated hydrogenation rates on the double bonds. Besides, the additional hydrogen speeds up the overall reaction by facilitating the isomerization step on limonene while impeding its reverse reaction, as isomerization of limonene is proved to be the determining step of the whole dehydroaromatization reaction. Furthermore, the presence of hydrogen dramatically decreases the apparent and true activity energy of the target dehydroaromatization reaction and reduces the impact of temperatures to such processes compared to that with a N2 gas carrier.
- Cui, Huimei,Zhang, Jingjing,Luo, Zhicheng,Zhao, Chen
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p. 66695 - 66704
(2016/08/02)
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- A 1,6-ring closure mechanism for (+)-δ-cadinene synthase?
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Recombinant (+)-δ-cadinene synthase (DCS) from Gossypium arboreum catalyzes the metal-dependent cyclization of (E,E)-farnesyl diphosphate (FDP) to the cadinane sesquiterpene δ-cadinene, the parent hydrocarbon of cotton phytoalexins such as gossypol. In contrast to some other sesquiterpene cyclases, DCS carries out this transformation with >98% fidelity but, as a consequence, leaves no mechanistic traces of its mode of action. The formation of (+)-δ-cadinene has been shown to occur via the enzyme-bound intermediate (3R)-nerolidyl diphosphate (NDP), which in turn has been postulated to be converted to cis-germacradienyl cation after a 1,10-cyclization. A subsequent 1,3-hydride shift would then relocate the carbocation within the transient macrocycle to expedite a second cyclization that yields the cadinenyl cation with the correct cis stereochemistry found in (+)-δ-cadinene. An elegant 1,10-mechanistic pathway that avoids the formation of (3R)-NDP has also been suggested. In this alternative scenario, the final cadinenyl cation is proposed to be formed through the intermediacy of trans, trans-germacradienyl cation and germacrene D. In addition, an alternative 1,6-ring closure mechanism via the bisabolyl cation has previously been envisioned. We report here a detailed investigation of the catalytic mechanism of DCS using a variety of mechanistic probes including, among others, deuterated and fluorinated FDPs. Farnesyl diphosphate analogues with fluorine at C2 and C10 acted as inhibitors of DCS, but intriguingly, after prolonged overnight incubations, they yielded 2F-germacrene(s) and a 10F-humulene, respectively. The observed 1,10-, and to a lesser extent, 1,11-cyclization activity of DCS with these fluorinated substrates is consistent with the postulated macrocyclization mechanism(s) en route to (+)-δ-cadinene. On the other hand, mechanistic results from incubations of DCS with 6F-FPP, (2Z,6E)-FDP, neryl diphosphate, 6,7-dihydro-FDP, and NDP seem to be in better agreement with the potential involvement of the alternative biosynthetic 1,6-ring closure pathway. In particular, the strong inhibition of DCS by 6F-FDP, coupled to the exclusive bisabolyl- and terpinyl-derived product profiles observed for the DCS-catalyzed turnover of (2Z,6E)-farnesyl and neryl diphosphates, suggested the intermediacy of α-bisabolyl cation. DCS incubations with enantiomerically pure [1- 2H1](1R)-FDP revealed that the putative bisabolyl-derived 1,6-pathway proceeds through (3R)-nerolidyl diphosphate (NDP), is consistent with previous deuterium-labeling studies, and accounts for the cis stereochemistry characteristic of cadinenyl-derived sesquiterpenes. While the results reported here do not unambiguously rule in favor of 1,6- or 1,10-cyclization, they demonstrate the mechanistic versatility inherent to DCS and highlight the possible existence of multiple mechanistic pathways.
- Faraldos, Juan A.,Miller, David J.,Gonzalez, Veronica,Yoosuf-Aly, Zulfa,Cascon, Oscar,Li, Amang,Allemann, Rudolf K.
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supporting information; experimental part
p. 5900 - 5908
(2012/05/07)
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- Triphenylpyrylium tetrafluoroborate-sensitized photochemistry of the terpenes sabinene, α-phellandrene, and α- and γ-terpinene
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The triphenypyrylium tetrafluoroborate (TPT)-sensitized reactions of several terpene donor molecules, including sabinene (1), α-phellandrene (4), α-terpinene (5) and γ-terpinene (6) give rise to significantly different products than reactions induced by other electron-transfer sensitizers, such as 1,4-dicyanobenzene (DCB). The divergent reactions require decidedly different key intermediates; the products obtained with TPT can be explained by dissociative recombination of the intermediate radical-radical cation pair in the triplet state, generating donor-derived biradicals.
- Climent, Maria-Jose,Miranda, Miguel Angel,Roth, Heinz Dieter
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p. 1563 - 1567
(2007/10/03)
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- The reaction of cyclic allylic alcohols with aliphatic alcohols in the presence of cerium(III) chloride
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Cyclic secondary and tertiary allylic alcohols react with primary aliphatic alcohols in the presence of cerium(III) chloride heptahydrate to give alkyl allylic ethers. When secondary or tertiary aliphatic alcohols are used 1,3-dienes are obtained from allylic alcohols heaving the 3-methyl-2-en-1-ol moiety (3-8, 13-15).
- Uzarewicz,Dresler
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p. 181 - 195
(2007/10/03)
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- CIDNP study and ab-initio calculations of rigid vinylcyclopropane systems: Evidence for delocalized 'ring-closed' radical cations
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The radical cations of three terpenes, sabinene, 1, and α-, 2, and β-thujene, 3, containing vinylcyclopropane functions held rigidly in either an anti- or syn-orientation, have been elucidated by CIDNP studies. The structures assigned to these species are discussed in view of their reactivities and compared with three simplified radical cations, 2-methylenebicyclo[3.1.0]hexane, 4, bicyclo[3.1.0]hex-2-ene, 5, and 5-methylbicyclo[3.1.0]hex-2-ene, 6, calculated by ab initio molecular orbital methods.
- Roth, Heinz D.,Weng, Hengxin,Herbertz, Torsten
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p. 10051 - 10070
(2007/10/03)
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- Hydrosilylation of unsaturated compounds
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A method for hydrosilylating an olefinically unsaturated compound comprising contacting the unsaturated compound with a source of silicon in the presence of an azo-containing free-radical catalyst, the hydrosilylated product being a useful crosslinking agent.
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- ENANTIOMERIC COMPOSITION OF MONOTERPENE HYDROCARBONS FROM THE LIVERWORT CONOCEPHALUM CONICUM
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Volatiles from the essential oil of the liverwort Conocephalum conicum were analysed.The chirality of the monoterpene hydrocarbons was studied by two-dimensional gas chromatography.All compounds except β-phellandrene showed high optical purity.For the identification of enantiomers, (+)-β-phellandrene and (-)-α-thujene were prepared from (+)-limonene and (+)-sabinene, respectively.Key Word Index: Conocephalum conicum; Hepaticae; liverwort; monoterpene hydrocarbons; (+)-β-phellandrene; (-)-α-thujene; chiral composition
- Valterova, Irena,Unelius, C. Rikard,Vrkoc, Jan,Norin, Torbjoern
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p. 3121 - 3124
(2007/10/02)
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- Thermodynamics of the Isomerisation of the p-Menthadienes and the Additivity of the Properties of Cyclic Hydrocarbons
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We have studied the equilibria and obtained the thermodynamic parameters for the isomerisation of nine p-menthadienes in the range 225-350 deg C.An approach has been proposed and shown to be effective for the additive calculation of the properties of aliphatic hydrocarbons: this is based on the introduction of additional effective characteristics for an atom which take into account its participation in the ring system of the molecule.
- Kabo, G. Ya.,Roganov, G. N.,Filippenko, Z. A.
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p. 1521 - 1522
(2007/10/02)
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- ISOMERIZATION EQUILIBRIUM OF THE p-MENTHADIENES IN THE VAPOR PHASE
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The isomerization equilibrium between nine p-menthadienes has been studied in the vapor phase at 250 deg C and their equilibrium ratios have been determined.A method for the quantitative GLC analysis of mixtures of isomeric p-menthadienes has been developed.
- Filippenko, Z. A.,Baranov, O. M.,Roganov, G. N.,Kabo, G. Ya.
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- Synthesis of Optically Active Triazolinediones and Examination of Their Utility for Inducing Asymmetry in Diels-Alder Cycloaddition Reactions
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(S)-(-)-α-Methylbenzylamine, dehydroabietylamine, and endo-bornylamine have been transformed into the optically pure triazolinediones via the respective isocyanates and urazoles.Their ability to discriminate between diastereomeric Diels-Alder transition states was determined in the case of two dienes, 2,4-p-menthadiene and α-phellandrene, which were prepared in racemic and optically active forms of known enantiomeric purity.Exhaustive cycloaddition to these dienes gave the needed pairs of adduct D reference points against which those obtained in the asymmetric induction studies could be compared.By this technique, simple plots of D vs. diastereomeric purity served to delineate not only the level of enantioselection but also the absolute configuration of the adducts.Due in part to their exceptionally high reactivity, the triazolinediones are not sufficiently selective to permit high levels of enantioselection.Rather, their usefulness lies in their ability to achieve nondestructive resolution of various nonobivously resolvable compounds.
- Paquette, Leo A.,Doehner, Robert F.
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p. 5105 - 5113
(2007/10/02)
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- Terpene hydroxysulfonic acids and corresponding hydroxysulfonate salts
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Optically active terpene hydroxysulfonate salts are made by sulfonating an optically active terpene epoxide of the p-menthane family, with a sulfonating agent selected from a sulfite, a bisulfite, or a thiosulfate.
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