• Title/Summary/Keyword: Allylic Alcohol

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Selective Reduction of Organic Compounds with Al-Trifluoromethanesulfonyldiisobutylalane. Comparison of Its Reactivity with Al-Methanesulfonyldiisobutylalane

  • Cha, Jin-Soon
    • Bulletin of the Korean Chemical Society
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    • v.32 no.1
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    • pp.219-224
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    • 2011
  • The new MPV type reagent, Al-trifluoromethanesulfonyldiisobutylalane ($DIBAO_3SCF_3$), has been prepared and its reducing characteristics in the reduction of selected organic compounds containing representative functional groups have been examined, and compared its reactivity with that of Al-methanesulfonyldiisobutylalane ($DIBAO_3SCH_3$) in order to understand the fluorine-substituent effect on its reactivity. In general, the reactivity of $DIBAO_3SCF_3$ appears to be much higher than that of $DIBAO_3SCH_3$, apparently due to the acidity increase by the electron-withdrawing fluorine-substituent. The reagent reduced aldehydes and ketones readily, but showed a perfect selectivity in the reduction of $\alpha,\beta$-unsaturated aldehydes and ketones to produce the corresponding allylic alcohols in an absolutely 100% purity. In addition, the reagent achieved the regioselective cleavage of phenyl- or/and alkyl-substituted epoxides to the less substituted alcohols in a perfect regioselectivity. Moreover, the reagent also showed an high stereoselectivity in the reduction of substituted cycloalkanones to produce the thermodynamically more stable alcohol epimers exclusively.

Novel Syntheses of Isomers of Damascenone from Ethyl 2,6,6-Trimethyl-4-oxo-2-cyclohexene-1-carboxylate

  • Lee, Woo-Young;Jang, Se-Young;Lee, Jun-Gu;Chae, Woo-Ki
    • Bulletin of the Korean Chemical Society
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    • v.12 no.1
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    • pp.31-35
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    • 1991
  • Three isomers of damascenone, odorous terpenic ketones, have been synthesized conveniently from a same starting material, ethyl 2,6,6-trimethyl-4-oxo-2-cyclohexene-1-carboxylate(1), which was easily available by the acid-catalyzed condensation of mesityl oxide or acetone with ethyl acetoacetate. ${\alpha}$-Damascenone(7) was prepared by converting the enone ester 1 into the corresponding tosylhydrazone(4), followed by treating with 4 molar equiv of allyllithium. ${\beta}$-Damascenone(12) was synthesized by chemoselective reduction of 1 with sodium borohydride/cerium chloride to give corresponding allylic alcohol 8, conversion of 8 into acetate 9, and thermal decomposition of 9 with DBU to afford ethyl ${\beta}$-safranate(10), followed by reaction with an excess amount of allyllithium. ${\gamma}$-Damascenone(15) was obtained by dehydration of 8 with boric acid to furnish ${\gamma}$-safranate(13), followed by treatment with 2 molar equiv of allyllithium.

A Total Synthesis of Nuciferal and Nuciferol

  • Lee, Woo-Young;Lee, Youn-Young;Lim, Kwang-Su;Goo, Yang-Mo;Park, Oee-Sook
    • Bulletin of the Korean Chemical Society
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    • v.9 no.6
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    • pp.379-381
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    • 1988
  • Racemic nuciferal(1) and nuciferol(2), the terpenic natural perfumeries, have been synthesized by a simple procedure. The benzylic halide 6; 1-(1-chloroethyl)-4-methylbenzene, was prepared by converting p-tolualdehyde(4) into 1-(p-tolyl)-1-ethanol(5), followed by convertion of 5 into corresponding chloride. The Grignard reagent of 6 was reacted with the bromoacetal 7, 2-(2-bromoethyl)-1,3-dioxolane, to give a crosscoupling product 8, which was hydrolysed to 4-(p-tolyl)-pentanal (9). The Wittig reaction of isopropylide 10 with 9 yielded arcurcumen(11). The stereospecific allylic oxidation of the gem-dimethyl olefin 11 with selenium dioxide afforded a trans-aldehyde, (${\pm}$)-1, which was reduced to corresponding alcohol, (${\pm}$)-2.

Selective Reduction of Carbonyl Compounds with Al-Alkoxydiisobutylalanes

  • 차진순;권오운;김종미;전중현;이영수;이형수;조성동
    • Bulletin of the Korean Chemical Society
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    • v.19 no.2
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    • pp.236-242
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    • 1998
  • Reaction of carbonyl compounds with Al-alkoxydiisobutylalane (DIBAOR, R=H, Et, i-Pr, t-Bu) has been investigated in detail so as to establish their usefulness as selective reducing agents in organic synthesis. The reagents appear to be extremely mild and can reduce only aldehydes and ketones effectively under mild conditions. All the other common organic functional groups are not affected by these reagents. The reagents can also reduce α,β-unsaturated aldehydes and ketones to the corresponding allylic alcohols without any detectable 1,4-reduction. Furthermore, the reagents show a highly chemoselective discrimination between aldehyde and ketone, between aldehydes, and between ketones. Even more remarkable is the stereoselective reduction of cyclic ketones to the thermodynamically more stable alcohol epimers.

Asymmetric Synthesis of 12(S)-HETE

  • Suh, Young-Ger;Kim, Jin-Kwan;Min, Kyung-Hoon;Seo, Seung-Yong;Lee, Bo-Young;Han, Young-Taek
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.364.2-364.2
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    • 2002
  • (S) and (R) 12-HETE. endogenous eicosanoids. have recently been discovered to be implicated in a number of important biological activities. In particular. it has recently been reported by us that both the capsaicin-activated channel of sensory neurons and the cloned capsaicin receptor (VR1) are activated by the eicosanoids including these metabolites. We report herein a novel and efficient asymmetric synthesis of highly enantiomerically enriched 12(S)-HETE via enzymatic kinetic resolution of the key allylic alcohol synthon. (omitted)

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Synthesis of Permethrin using Ester Enolate Claisen Rearrangement (에스테르엔올 음이온의 Claisen 자리옮김 반응에 의한 Permethrin의 합성)

  • In-Kyu Kim;Suk-Ku Kang;Jang-Hoo Hong
    • Journal of the Korean Chemical Society
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    • v.30 no.6
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    • pp.548-552
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    • 1986
  • A stereoselective synthesis of 3-phenoxybenzyl (${\pm}$)-cis and trans-3-(2,2-dichlorovinyl)-2,2-dimethyl-1-cyclopropanecarboxylic acid starting from readily available 2-methyl-3-buten-2-ol($\underline{2}$) is described. Allylic rearrangement of 2-methyl-3-buten-2-ol, in the presence of acetic acid and acetic anhydride gave 3-methyl-2-butenyl acetate($\underline{3}$). The [3,3] sigmatropic rearrangement of the allyl acetate($\underline{3}$), as the silylketene acetal, produced the ${\gamma},\;{\delta}$-unsaturated acid($\underline{4}$). Treatment of 3,3-dimethyl-4-pentenoic acid($\underline{4}$) with SOCl2 followed by esterification with 3-phenoxybenzyl alcohol yielded 3, 3-dimethyl-4-pentenoic acid ester($\underline{5}$). Addition of carbon tetrachloride to the olefin ester($\underline{6}$) furnished 4,6,6,6-tetrachloro-3,3-dimethylhexanoic acid ester ($\underline{7}$). Cyclization with potassium t-butoxide and elimination of hydrogen chloride afforded 3-phenoxybenzyl (${\pm}$) cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethyl-1-cyclopropanecarboxylic acid.

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Polyacetylene Compounds from Panax ginseng C.A. Meyer (인삼의 Polyacetylene 화합물)

  • Shim Sang Chul;Chang Suk-Ku
    • Proceedings of the Ginseng society Conference
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    • 1988.08a
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    • pp.122-128
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    • 1988
  • Several major polyacetylene compounds were isolated from the petroleum-ether fraction of fresh Korean ginseng roots through solvent fractionation. partition and silica gel column chromatography. Further separation of acetylenic compounds was accomplished by bonded normal phase HPLC utilizing a moderately nonpolar microparticulate column. The preparative separation for the various spectral measurements was carried out by low pressure preparative liquid chromatography. The chemical structure of these polyacetylenes separated was determined by UV. IR/FTIR. $^{1}H$ NMR. mass spectral and elemental analysis. These are identified to be heptadeca-1-en-4.6-diyn-3.9.l0.-triol [1] heptadeca-1.9-dien-4.6-diyn-3-ol. heptadeca-1.8-dien-4.6-diyn-3.10-diol and the 4th was denatured polyacetylene. heptadeca-1.4-dien-6.8-diyn-3.10-diol. Two different p-substituted benzoates of panaxynol were synthesized for the determination of exciton chirality. The circular dichroism spectra in the UV region show that panaxynol p-bromobenzoate and p-dimethyl-aminobenzoate constitute negative exciton chirality [2]. Isolated major polyacetylene compounds were irradiated in aerated solution with 300 nm UV light to obtain the oxidized product at the allylic alcohol center to corresponding carbonyl compounds such as heptadeca-1-en-4.6-diyn-9.10-diol-3-one and heptadeca-1.9-dien-4.6-diyn-3-one. These photooxidation compounds have en-on-diyne chromophore and undergo nucleophilic addition reaction with methanol to yield ${\beta}-methoxy$ carbonyl compounds such as heptadeca-9-en-4.6-diyn-1-methoxy-3-one and heptadeca-4.6-diyn-1-methoxy-9.10-diol-3-one.

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Sesquiterpenoids Bioconversion Analysis by Wood Rot Fungi

  • Lee, Su-Yeon;Ryu, Sun-Hwa;Choi, In-Gyu;Kim, Myungkil
    • 한국균학회소식:학술대회논문집
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    • 2016.05a
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    • pp.19-20
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    • 2016
  • Sesquiterpenoids are defined as $C_{15}$ compounds derived from farnesyl pyrophosphate (FPP), and their complex structures are found in the tissue of many diverse plants (Degenhardt et al. 2009). FPP's long chain length and additional double bond enables its conversion to a huge range of mono-, di-, and tri-cyclic structures. A number of cyclic sesquiterpenes with alcohol, aldehyde, and ketone derivatives have key biological and medicinal properties (Fraga 1999). Fungi, such as the wood-rotting Polyporus brumalis, are excellent sources of pharmaceutically interesting natural products such as sesquiterpenoids. In this study, we investigated the biosynthesis of P. brumalis sesquiterpenoids on modified medium. Fungal suspensions of 11 white rot species were inoculated in modified medium containing $C_6H_{12}O_6$, $C_4H_{12}N_2O_6$, $KH_2PO_4$, $MgSO_4$, and $CaCl_2$ for 20 days. Cultivation was stopped by solvent extraction via separation of the mycelium. The metabolites were identified as follows: propionic acid (1), mevalonic acid lactone (2), ${\beta}$-eudesmane (3), and ${\beta}$-eudesmol (4), respectively (Figure 1). The main peaks of ${\beta}$-eudesmane and ${\beta}$-eudesmol, which were indicative of sesquiterpene structures, were consistently detected for 5, 7, 12, and 15 days These results demonstrated the existence of terpene metabolism in the mycelium of P. brumalis. Polyporus spp. are known to generate flavor components such as methyl 2,4-dihydroxy-3,6-dimethyl benzoate; 2-hydroxy-4-methoxy-6-methyl benzoic acid; 3-hydroxy-5-methyl phenol; and 3-methoxy-2,5-dimethyl phenol in submerged cultures (Hoffmann and Esser 1978). Drimanes of sesquiterpenes were reported as metabolites from P. arcularius and shown to exhibit antimicrobial activity against Gram-positive bacteria such as Staphylococcus aureus (Fleck et al. 1996). The main metabolites of P. brumalis, ${\beta}$-Eudesmol and ${\beta}$-eudesmane, were categorized as eudesmane-type sesquiterpene structures. The eudesmane skeleton could be biosynthesized from FPP-derived IPP, and approximately 1,000 structures have been identified in plants as essential oils. The biosynthesis of eudesmol from P. brumalis may thus be an important tool for the production of useful natural compounds as presumed from its identified potent bioactivity in plants. Essential oils comprising eudesmane-type sesquiterpenoids have been previously and extensively researched (Wu et al. 2006). ${\beta}$-Eudesmol is a well-known and important eudesmane alcohol with an anticholinergic effect in the vascular endothelium (Tsuneki et al. 2005). Additionally, recent studies demonstrated that ${\beta}$-eudesmol acts as a channel blocker for nicotinic acetylcholine receptors at the neuromuscular junction, and it can inhibit angiogenesis in vitro and in vivo by blocking the mitogen-activated protein kinase (MAPK) signaling pathway (Seo et al. 2011). Variation of nutrients was conducted to determine an optimum condition for the biosynthesis of sesquiterpenes by P. brumalis. Genes encoding terpene synthases, which are crucial to the terpene synthesis pathway, generally respond to environmental factors such as pH, temperature, and available nutrients (Hoffmeister and Keller 2007, Yu and Keller 2005). Calvo et al. described the effect of major nutrients, carbon and nitrogen, on the synthesis of secondary metabolites (Calvo et al. 2002). P. brumalis did not prefer to synthesize sesquiterpenes under all growth conditions. Results of differences in metabolites observed in P. brumalis grown in PDB and modified medium highlighted the potential effect inorganic sources such as $C_4H_{12}N_2O_6$, $KH_2PO_4$, $MgSO_4$, and $CaCl_2$ on sesquiterpene synthesis. ${\beta}$-eudesmol was apparent during cultivation except for when P. brumalis was grown on $MgSO_4$-free medium. These results demonstrated that $MgSO_4$ can specifically control the biosynthesis of ${\beta}$-eudesmol. Magnesium has been reported as a cofactor that binds to sesquiterpene synthase (Agger et al. 2008). Specifically, the $Mg^{2+}$ ions bind to two conserved metal-binding motifs. These metal ions complex to the substrate pyrophosphate, thereby promoting the ionization of the leaving groups of FPP and resulting in the generation of a highly reactive allylic cation. Effect of magnesium source on the sesquiterpene biosynthesis was also identified via analysis of the concentration of total carbohydrates. Our current study offered further insight that fungal sesquiterpene biosynthesis can be controlled by nutrients. To profile the metabolites of P. brumalis, the cultures were extracted based on the growth curve. Despite metabolites produced during mycelia growth, there was difficulty in detecting significant changes in metabolite production, especially those at low concentrations. These compounds may be of interest in understanding their synthetic mechanisms in P. brumalis. The synthesis of terpene compounds began during the growth phase at day 9. Sesquiterpene synthesis occurred after growth was complete. At day 9, drimenol, farnesol, and mevalonic lactone (or mevalonic acid lactone) were identified. Mevalonic acid lactone is the precursor of the mevalonic pathway, and particularly, it is a precursor for a number of biologically important lipids, including cholesterol hormones (Buckley et al. 2002). Farnesol is the precursor of sesquiterpenoids. Drimenol compounds, bi-cyclic-sesquiterpene alcohols, can be synthesized from trans-trans farnesol via cyclization and rearrangement (Polovinka et al. 1994). They have also been identified in the basidiomycota Lentinus lepideus as secondary metabolites. After 12 days in the growth phase, ${\beta}$-elemene caryophyllene, ${\delta}$-cadiene, and eudesmane were detected with ${\beta}$-eudesmol. The data showed the synthesis of sesquiterpene hydrocarbons with bi-cyclic structures. These compounds can be synthesized from FPP by cyclization. Cyclic terpenoids are synthesized through the formation of a carbon skeleton from linear precursors by terpene cyclase, which is followed by chemical modification by oxidation, reduction, methylation, etc. Sesquiterpene cyclase is a key branch-point enzyme that catalyzes the complex intermolecular cyclization of the linear prenyl diphosphate into cyclic hydrocarbons (Toyomasu et al. 2007). After 20 days in stationary phase, the oxygenated structures eudesmol, elemol, and caryophyllene oxide were detected. Thus, after growth, sesquiterpenes were identified. Per these results, we showed that terpene metabolism in wood-rotting fungi occurs in the stationary phase. We also showed that such metabolism can be controlled by magnesium supplementation in the growth medium. In conclusion, we identified P. brumalis as a wood-rotting fungus that can produce sesquiterpenes. To mechanistically understand eudesmane-type sesquiterpene biosynthesis in P. brumalis, further research into the genes regulating the dynamics of such biosynthesis is warranted.

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