- Copper-Catalyzed Dehydrogenative Diels-Alder Reaction
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A practical and effective copper-catalyzed dehydrogenative Diels-Alder reaction of gem-diesters and ketone with dienes has been established. The active dienophiles were generated in situ via a radical-based dehydrogenation process, which reacted with a wide variety of dienes to afford various polysubstituted cyclohexene derivatives in good to excellent yields.
- Jiang, Bing,Liang, Qiu-Ju,Han, Yu,Zhao, Meng,Xu, Yun-He,Loh, Teck-Peng
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supporting information
p. 3215 - 3219
(2018/06/11)
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- Ravynic acid, an antibiotic polyeneyne tetramic acid from: Penicillium sp. elucidated through synthesis
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A new antibiotic natural product, ravynic acid, has been isolated from a Penicillium sp. of fungus, collected from Ravensbourne National Park. The 3-acylpolyenyne tetramic acid structure was definitively elucidated via synthesis. Highlights of the synthetic method include the heat induced formation of the 3-acylphosphorane tetramic acid and a selective Wittig cross-coupling to efficiently prepare the natural compounds carbon skeleton. The natural compound was shown to inhibit the growth of Staphylococcus aureus down to concentrations of 2.5 g mL-1.
- Myrtle,Beekman,Barrow
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p. 8253 - 8260
(2016/09/09)
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- Synthesis and characterization of novel phosphonocarboxylate inhibitors of RGGT
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Phosphonocarboxylate (PC) analogs of the anti-osteoporotic drugs, bisphosphonates, represent the first class of selective inhibitors of Rab geranylgeranyl transferase (RabGGTase, RGGT), an enzyme implicated in several diseases including ovarian, breast and skin cancer. Here we present the synthesis and biological characterization of an extended set of this class of compounds, including lipophilic derivatives of the known RGGT inhibitors. From this new panel of PCs, we have identified an inhibitor of RGGT that is of similar potency as the most active published phosphonocarboxylate, but of higher selectivity towards prenyl pyrophosphate synthases. New insights into structural requirements are also presented, showing that only PC analogs of the most potent 3rd generation bisphosphonates inhibit RGGT. In addition, the first phosphonocarboxylate-derived GGPPS weak inhibitor is reported.
- Coxon, Fraser,Joachimiak, ?ukasz,Najumudeen, Arafath Kaja,Breen, George,Gmach, Joanna,Oetken-Lindholm, Christina,Way, Rebecca,Dunford, James,Abankwa, Daniel,B?azewska, Katarzyna M.
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supporting information
p. 77 - 89
(2014/07/22)
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- Total synthesis of (±)-merrilactone A
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The total synthesis of racemic merrilactone A (a neurotrophic agent) is described, featuring simultaneous and stereospecific creation of the C4 and C5 Stereocenters via a notable silyloxyfuran Nazarov cyclization. Full details of the successful synthetic strategy are given, as well as several examples of the interesting reactivity of intermediates that were prepared and studied during the execution of the total synthesis. A detailed investigation of the Lewis acid-catalyzed Nazarov cyclization of silyloxyfurans was conducted, including a systematic study of substrate scope and limitations. In addition, experiments were conducted that suggest the participation of Lewis acidic silicon species in the Nazarov cyclization.
- He, Wei,Huang, Jie,Sun, Xiufeng,Frontier, Alison J.
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p. 300 - 308
(2008/09/18)
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- Synthetic studies aimed at the elucidation of the stereostructure of the aggregation pheromone, 2-methyl-6-(4′-methylenebicyclo[3.1.0]hexyl)hept-2-en-1-ol, produced by the male stink bug Erysarcoris lewisi
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The male-produced aggregation pheromone of the stink bug Erysarcoris lewisi Distant was shown to be one of the two diastereomers of (2Z,6R)-2-methyl-6-(4′-methylenebicyclo[3.1.0]hexyl)hept-2-en-1-ol by synthesizing and bioassaying (2E,6R)-, (2E,6S)-, (2Z,6R)-, and (2Z,6S)-isomers. These were synthesized from the enantiomers of citronellal by employing an intramolecular α-ketocarbene addition to a double bond and the E-selective or Z-selective olefination of a formyl group as the key steps. A reliable method was developed for the preparation of ethyl 2-(di-o-tolylphosphono)propanoate, Ando's reagent for Z-selective olefination.
- Mori, Kenji
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p. 838 - 846
(2008/02/08)
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- Synthesis of spiro[4.5]decane and bicyclo[4.3.0]nonane ring systems by self-cyclization of (Z)- and (E)-2-(trimethylsilylmethyl)pentadienal derivative
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The two title carbon frameworks were synthesized utilizing a new type of iron-induced cyclization reaction of 2-(trimethylsilylmethyl)pentadienal. 2-Methylspiro[4.5]dec-2-en-1-one was obtained from (Z)- and (E)-4- cyclohexylidene-2-(trimethylsilylmethyl)but-2-enal. It was found that the (Z)-substrate isomerized to (E)-intermediate followed by cyclization to afford the initial product, 2-methylenespiro[4.5]dec-3-en-1-ol, which was isomerized to the above product. The cyclization of 4-(4-alkyl)cyclohexylidene-2- (trimethylsilylmethyl)but-2-enal proceeded stereoselectively. While, (E)-3-(cyclohex-1-en-1-yl)-2-(trimethylsilylmethyl)prop-2-en-1-al cyclized immediately affording 8-methylenebicyclo[4.3.0]non-9-en-7-ol. The corresponding (Z)-isomer gave several cyclization products as a complex mixture.
- Kuroda, Chiaki,Honda, Shigenobu,Nagura, Yuki,Koshio, Hiroyuki,Shibue, Taku,Takeshita, Tokio
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p. 319 - 331
(2007/10/03)
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- Synthesis and biological evaluation of cycloalkylidene carboxylic acids as novel effectors of Ras/Raf interaction
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The protooncogenes Ras and Raf play important roles in signal transduction pathways regulated by mitogen-activated protein kinases. Mutations of Ras that arrest the protein in its active state are frequently implicated in tumor formation. We used Ras and Raf proteins in the yeast two-hybrid system to search for natural or synthesized substances capable of modulating Ras/Raf interaction by specifically binding to one of the interacting partners. We found that cycloalkylidene carboxylic acids enhanced Ras/Raf interaction by acting on the cysteine-rich domain of Raf. Several analogues of the active substance 2-cyclohexylidene propanoic acid were synthesized and the importance of the semicyclic double bond in the stabilization of Ras/Raf interaction was demonstrated. Variation of the size and the substituents of the cyclic system as well as the length of the carboxylic acid resulted in enhanced Ras/Raf interaction.
- Friese, Anke,Hell-Momeni, Katja,Zündorf, Ilse,Winckler, Thomas,Dingermann, Theodor,Dannhardt, Gerd
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p. 1535 - 1542
(2007/10/03)
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- A useful synthesis of diethyl 1-substituted vinylphosphonates
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A variety of diethyl 1-substituted vinylphosphonates 8 has been conveniently synthesized by piperidine catalyzed decarboxylative condensation of 2-diethoxyphosphorylalkanoic acids and 2-diethoxyphosphorylalkenoic acids 7 with formaldehyde.
- Krawczyk,Koszuk,Bodalski
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p. 1123 - 1128
(2007/10/03)
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- Nazarov cyclization of 4-cycloalkylidene-5-(trimethylsilyl)pent-1-en-3-one derivatives. Synthesis of spiro[4.5]decane, Spiro[4.4]nonane, and Their derivatives
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Spiro[4.5]decane and spiro[4.4]nonane ring systems were synthesized by FeCl3-induced Nazarov cyclization of α-(trimethylsilylmethyl)divinyl ketone derivatives. It was found that the double bond position of the product is controlled by the presence/absence of α'-substituent, while trimethylsilyl group is essential to obtain the products in good yields. Spiro[4.4]nonanes having exo-methylene group underwent rearrangement to bicyclo[4.3.0]nonanes. (C) 2000 Elsevier Science Ltd.
- Kuroda,Koshio,Koito,Sumiya,Murase,Hirono
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p. 6441 - 6455
(2007/10/03)
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- Synthesis and SAR of 1-alkyl-2-phenylethylamine derivatives designed from N,N-dipropyl-4-methoxy-3-(2-phenylethoxy)phenylethylamine to discover σ1 ligands
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The synthesis and structure-activity relationships (SAR) of 1-alkyl-2- phenylethylamine derivatives 5-8 designed from N,N-dipropyl-2-[4-methoxy-3- (2-phenylethoxy)phenyl]ethylamine hydrochloride (1, NE-100) are presented. The SAR between compound 1 and 1-alkyl-2-phenylethylamine derivatives suggested that the alkyl group on the 1-position carbon of 2-[4-methoxy-3-(2- phenylethyl)phenyl]ethylamine derivatives played the role of one of the propyl groups on the aminic nitrogen of compound 1. (-)-N-Propyl-1-butyl-2- [4-methoxy-3-(2-phenylethoxy)phenyl]ethylamine hydrochloride ((-)-6d, NE-537) and (-)-N-propyl-1-(3-methybutyl)-2-[4-methoxy-3-(2- phenylethoxy)phenyl]ethylamine hydrochloride ((-)-6i, NE-535), typical compounds in this series, have potent and selective σ1 affinity.
- Nakazato, Atsuro,Kumagai, Toshihito,Ohta, Kohmei,Chaki, Shigeyuki,Okuyama, Shigeru,Tomisawa, Kazuyuki
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p. 3965 - 3970
(2007/10/03)
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- Proto- and iodo-lactonization reaction of substituted α,β: γ,δ- unsaturated carboxylic acid
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Iodolactonization of 4,5-disubstituted 2-(trimethylsilylmethyl)- and 2- methyl-penta-2,4-dienoic acids was studied. The latter afforded the corresponding iodolactone in good yield by treatment with I2 in MeCN. Iodolactone was also obtained by treatment with I2/NaHCO3/CHCl3/H2O in the presence of cerium(IV) salt as an additive. It was found that protolactonization proceeds by the aid of the trimethylsilyl group, while it prevents iodolactonization.
- Kuroda, Chiaki,Tang, Chen Ying,Tanabe, Makoto,Funakoshi, Masabumi
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p. 1583 - 1587
(2007/10/03)
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- Horner-Emmons reaction in the synthesis of esters of unsaturated acids from aclamantane series and related carcass compounds
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In reaction with triethyl phosphonoacetate in the presence of sodium hydride at 100-120°C ketones related to adamantane, 1,3-diazaadamantane, and bicyclo[3.3.1]nonane with a carbonyl group either in the ring or in the side chain, and also aldehydes from adamantane series transform into acryl acid derivatives. The reaction of triethyl iodophosphonoacetate with 1-adamantanecarboxaldehyde yields a derivative of propargylic acid. Phosphonate reagents prepared from 4-azahomoadamantane give the corresponding unsaturated esters already on reacting with acetaldehyde at 30°C.
- Miryan,Isaev,Kovaleva,Petukh,Dvornikova,Kardakova,Yurchenko
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p. 857 - 861
(2007/10/03)
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- Enantioselective hydrogenation of α,β-unsaturated acids. Substrate-modifier interaction over cinchonidine modified Pd/Al2O3
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X-Ray diffraction, IR measurements and catalytic hydrogenation of various substituted acrylic acids in apolar solvents, as well as molecular modelling provide new insight into the nature of the cinchonidine-substrate interaction and a general rule to predict the major enantiomer.
- Borszeky,Mallat,Baiker
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p. 3745 - 3753
(2007/10/03)
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- Acetic acid derivatives and their production
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Compounds of formula STR1 where n is an integer from 1 to 12, R and R1 are the same or different and are hydrogen or C1 to C6 linear or branched alkyl as well as their physiologically active salts and amides thereof and the enantiomers, mixtures and racemates are disclosed. Intermediates useful in preparing the above compounds are also disclosed as are processes for preparing these compounds.
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- A Chemoenzymatic Synthesis of Enantiomerically Pure (R)- and (S)-2-Methyldecan-1-ol
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(R)- and (S)-methyldecan-1-ol 3a has been prepared in >98percent enantiomeric excess (ee) by transesterification with vinyl acetate in chloroform in the presence of Pseudomonas fluorescens lipase.Oxidation of the alcohol 3a affords nearly optically pure 2-methyldecanoic acid 3b.
- Ferraboschi, Patrizia,Grisenti, Paride,Manzocchi, Ada,Santaniello, Enzo
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p. 1159 - 1162
(2007/10/02)
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- Reaction of Diethyl Phosphorochloridite with Enolates: A General Method for Synthesis of β-Keto Phosphonates and α-Phosphono Esters through C-P Bond Formation
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The reaction of ketone enolates with diethyl phosphorochloridite, followed by air oxidation of the intermediate reaction products, has proven to be a general and convenient method for preparation of β-keto phosphonates.Fourteen β-keto phosphonates have been prepared by this method, in an average yield greater than 60percent.This procedure also appears to be applicable to preparation of both α-phosphono aldehydes and α-phosphono esters.Although special precautions may be necessary to avoid aldol condensation during formation of aldehyde enolates, in two cases it was shown that the resulting enolates react readily with diethyl chlorophosphite.Finally, a set of five ethyl esters was converted to α-phosphono esters by this method.Yields of the α-phosphono esters are influenced by steric hindrance at the enolate carbon, but the average yield for this series was ca. 70percent.Because this synthetic method relies upon an electrophilic phosphorus reagent for formation of the C-P bond, it is complementary to the traditional Arbuzov synthesis.On the basis of the 21 examples presented here, it appears to be more widely applicable.
- Lee, Koo,Wiemer, David F.
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p. 5556 - 5560
(2007/10/02)
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- Synthesis of α-Phosphono Lactones and Esters through a Vinyl Phosphate-Phosphonate Rearrangement
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Upon treatment with base, the diethyl vinyl phosphate derivatives of five-, six-, and seven-membered-ring lactones undergo rearrangement to α-phosphono lactones in very good yields.Because the vinyl phosphates can be prepared in situ, these α-phosphono lactones can be obtained from the parent lactones in a one-flask protocol, making this methodology a convenient alternative to the traditional Arbuzov synthesis.An analogous reaction sequence can be used to prepare some α-phosphono esters, but yields are generally lower and the rearrangement becomes minimal with esters hindered at the β-position.
- Jackson, John A.,Hammond, Gerald B.,Wiemer, David F.
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p. 4750 - 4754
(2007/10/02)
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- Carbanions phosphonate prepares par voie electrochimique: formation et reactivite vis-a-vis d'un aldehyde
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Reactivity towards p-methoxybenzaldehyde (ArCHO) of electrochemically generated phosphonate carbanions has been investigated.Electrolyses were carried out at a mercury cathode in DMF and two routes to the desired carbanion have been compared: (i) Deprotonation of phosphonates of general formula (EtO)2P(O)CHYW (Y = W = Cl; Y = H, W = Cl; Y = Cl, W = CO2Et; Y = H, W = CO2Et; Y = CH3, W = CO2Et; Y = Cl, W = CH3), by the bases resulting from the electroreduction of azobenzene; addition of the carbanion formed onto the carbonyl group takes place and leads to the adduct (EtO)2P(O)CYW(Ar)O-. (ii) Two-electron reduction of halophosphonates (EtO)2P(O)CXYW (X = Cl, Y and W as above; X = Br, W = CO2Et, Y = Cl, Br, or CH3); when no H atom is present on the carbon bearing the phosphonate group (Y and W no = H), the same evolution leading to the above adduct is observed, on the contrary, when Y = H, the electrogenerated carbanion deprotonates the substrate and the resulting carbanion (EtO)2P(O)CXW reacts with the aldehyde; giving the adduct (EtO)2P(O)CXW(Ar)O-.Evolution of the intermediate adduct depends on the substituents Y (or X) and W: when W = CO2Et, whatever the nature of Y (or X), diethyl phosphate is eliminated with formation of the ethylenic ArCH=CWY (or X) (Wittig-Horner reaction); the same evolution is observed when Y = W = Cl.When W = Cl and Y = H or CH3, the final product is the phosphonate epoxyde resulting from chloride elimination (Darzens reaction).Chemo- and stereoselectivity depend only on the nature of Y and W but are independent of the mode of generation of the carbanion.Yields are limited by side-protonation reactions, which are related to the basicity of the phosphonate carbanions.Analysis of the results permits selection of the optimal electrolysis conditions for purposes of synthesis.Key words: electrosynthesis, electrogenerated bases, phosphonates, Wittig-Horner.
- Le Menn, Jean-Christophe,Sarrazin, Jean,Tallec, Andre
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p. 1332 - 1343
(2007/10/02)
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- PHOTODECONJUGAISON ENANTIOSELECTIVE D'ESTERS ET DE LACTONES CONJUGUEES EN PRESENCE D'EPHEDRINE
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α,β-unsaturated esters and α-alkylidene lactones bearing one γ-hydrogen on the unsaturated chain, were deconjugated by irradiation with UV light (λ=254 nm).When the reaction was carried out in the presence of (+) or (-) ephedrine, an enantioselective C-protonation of the photodienolic intermediate led to the deconjugated ester with an enantiomeric excess up to 30 percent.The scape of the reaction and the configuration of the new asymmetric center are discussed.
- Henin, Francoise,Mortezaei, Reza,Muzart, Jacques,Pete, Jean-Pierre,Piva, Oliverier
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p. 6171 - 6196
(2007/10/02)
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- α-LITHIOALKYLPHOSPHONATES AS FUNCTIONAL GROUP CARRIERS. AN IN SITU ACRYLIC ESTER SYNTHESIS
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Condensation of α-lithioalkylphosphonates with diethylcarbonate in the presence of LDA generates carbethoxyalkylphosphonate anions which upon treatment at room temperature with aldehydes constitutes an in situ acrylic ester synthesis.
- Tay, M. K.,About-Jaudet, E.,Collignon, N.,Teulade, M. P.,Savignac, Ph.
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p. 1349 - 1362
(2007/10/02)
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- SYNTHESIS OF THE PHEROMONES, (E)-3,7-DIMETHYL-2,7-OCTADIENYL PROPIONATE, (E)-3,7-DIMETHYL-2-OCTENE-1,8-DIOL AND FRONTALIN FROM A COMMON INTERMEDIATE
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Ketal ester 9 has been prepared in five steps from methyl levulinate 4 (scheme 1).The propionate 1, diol 2 and (+/-) frontalin 3 were prepared from ester 9 employing the routes shown in scheme 2,3 and 4 respectively.The branched chain alkenes 13 and 20 were prepared conveniently from the primary alcohols 11 and 10 following the procedure of S.Wolff.Triethyl phosphonopropionate 7 has been prepared by methylating triethylphosphonoacetate with methyl iodide in the presence of sodium hydride.
- Dhokte, U. P.,Rao, A. S.
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p. 811 - 822
(2007/10/02)
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- Biohydrogenation of Unsaturated Compounds by Saccharomyces cerevisiae. Part 1. Stereochemical Aspects of the Reaction and Preparation of Useful Bifunctional Chiral Synthons
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Ethyl 4,4-dimethoxy-3-methylbut-2-enoate (1; R=CO2Et) has been prepared as a mixture of (E)- and (Z)-isomers, the (E)/(Z) ratio depending on the base used.Each isomeric mixture of (1a) and (1b) has been used as substrate for biohydrogenation with fermenting Saccharomyces cerevisiae (baker's yeast) and the (Z)-isomer seems to be the preferred substrate. (E)-Unsaturated alcohols such as (3a) and (5d) are not reduced to the corresponding saturated hydroxy derivatives by baker's yeast.The (E)-aldehyde (3c) and its acetal (3d) are mainly reduced to the corresponding (E)-alcohol (3a), the saturated hydroxy ester (2a) being formed to a minor extent, especially with (3d).In contrast, biohydrogenation is also successful with the (E)-isomers of compounds (3e), (3f), and (3b) (R2=alkyl or alkenyl).If the allylic oxygenated group to be reduced is not α-methyl substituted, reduction to the corresponding saturated alcohols readily occurs with the (E)-isomers as in the case of (5f).For this last biohydrogenation, the stereochemistry of the methyl-bearing carbon has been established by chemical correlations.The α,β-disubstituted allylic acetal (6a) is not biohydrogenated by the yeast, but a mixture of unsaturated hydroxy ester (6b) and γ-hydroxy lactone (8) is recovered from the incubation.
- Ferraboschi, Patrizia,Grisenti, Paride,Casati, Rosangela,Fiecchi, Alberto,Santaniello, Enzo
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p. 1743 - 1748
(2007/10/02)
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- PREPARATION QUASI QUANTITATIVE DE PHOSPHONATES β-CARBONYLES PAR L'EMPLOI D'UNE BASE RELAIS, LE DIPAL
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Preparation of oxo-2 alkylphosphonates by anionic route is a process of limited scope.The low yields often encountered in the initial phosphonylation step are certainly due to regeneration of the departure phosphonate through acid-base exchanges.This drawback can be overcome by proper choice of the metalating agent.The use of LDA makes the procedure efficient and most stoechiometric, and it lends itself to the preparation of a wide range of β-ketophosphonates free of by-products.
- Aboujaoude, Elie Elia,Collignon, Noel,Teulade, Marie-Paule,Savignac, Philippe
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- Mechanism of Formation of α,β-Unsaturated Esters in the Reaction of Ethyl Mercaptoacetate Dianion with Carbonyl Compounds
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Dianion derived fron ethyl mercaptoacetate undergoes aldol type reaction with a carbonyl compounds to give an adduct, which exhibited low diastereoselectivity.However, the adducts obtained by the reaction with a variety of aldehydes were subsequently treated with ethyl chloroformate in the presence of trivalent phosphorus compound to give (E)-isomers of α,β-unsaturated esters in high yields with greater than 85percent stereoselectivity regardless of the stereochemistry of the diastereomers of the adducts.The stereochemical mechanism and application of this reaction were studied in detail.
- Matsui, Syuichi
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p. 426 - 434
(2007/10/02)
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- SYNTHESE DE PHOSPHONATES β-CARBONYLES I. PAR VOIE CARBANIONIQUE
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Condensation of a lithiated phosphonate carbanion not bearing a stabilizing group with a carbonyl precursor (amide or ester) gives an intermediate oxyanion which decomposes on hydrolysis to yield a β-carbonyl phosphonate.This type of reaction gives access to a large group of phosphonates: β-ketophosphonates, phosphonic aldehydes, phosphonopyruvates etc.The reaction conditions are discussed.
- Aboujaoude, Elie Elia,Collignon, Noel,Savignac, Philippe
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- PHOSPHONOACYL PROLINES AND RELATED COMPOUNDS
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New phosphonoacyl prolines and related compounds have the general formula STR1 wherein R 1 and R 2 each is hydrogen, lower alkyl, lower alkenyl, unsustituted or substituted phenyl-lower alkyl, or a metal ion;R 3 is hydrogen or lower alkyl; R 4 is hydrogen, lower alkyl, phenyl-lower alkyl or a metal ion; andN IS 0 OR 1. These compounds are useful as hypotensive agents.
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