- Stereospecificity of the dehydratase domain of the erythromycin polyketide synthase
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The dehydratase (DH) domain of module 4 of the 6-deoxyerythronolide B synthase (DEBS) has been shown to catalyze an exclusive syn elimination/syn addition of water. Incubation of recombinant DH4 with chemoenzymatically prepared anti-(2R,3R)-2-methyl-3-hydroxypentanoyl-ACP (2a-ACP) gave the dehydration product 3-ACP. Similarly, incubation of DH4 with synthetic 3-ACP resulted in the reverse enzyme-catalyzed hydration reaction, giving an ~3:1 equilbrium mixture of 2a-ACP and 3-ACP. Incubation of a mixture of propionyl-SNAC (4), methylmalonyl-CoA, and NADPH with the DEBS β-ketoacyl synthase-acyl transferase [KS6][AT6] didomain, DEBS ACP6, and the ketoreductase domain from tylactone synthase module 1 (TYLS KR1) generated in situ anti-2a-ACP that underwent DH4-catalyzed syn dehydration to give 3-ACP. DH4 did not dehydrate syn-(2S,3R)-2b-ACP, syn-(2R,3S)-2c-ACP, or anti-(2S,3S)-2d-ACP generated in situ by DEBS KR1, DEBS KR6, or the rifamycin synthase KR7 (RIFS KR7), respectively. Similarly, incubation of a mixture of (2S,3R)-2-methyl-3- hydroxypentanoyl-N-acetylcysteamine thioester (2b-SNAC), methylmalonyl-CoA, and NADPH with DEBS [KS6][AT6], DEBS ACP6, and TYLS KR1 gave anti-(2R,3R)-6-ACP that underwent syn dehydration catalyzed by DEBS DH4 to give (4R,5R)-(E)-2,4- dimethyl-5-hydroxy-hept-2-enoyl-ACP (7-ACP). The structure and stereochemistry of 7 were established by GC-MS and LC-MS comparison of the derived methyl ester 7-Me to a synthetic sample of 7-Me.
- Valenzano, Chiara R.,You, Young-Ok,Garg, Ashish,Keatinge-Clay, Adrian,Khosla, Chaitan,Cane, David E.
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Read Online
- SYNTHESIS OF RACEMIC DOMINCALURE - THE AGGREGATION PHEROMONE OF THE LESSER GRAIN BORER Rhyzopertha dominica
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The sec-amyl esters of 2-methylpent-2E-enoic and 2,4-dimethylpent-2E-enoic acids, constituting the aggregation pheromone of the lesser grain borer Rhyzopertha dominica, have been synthesized stereospecifically in high yield from the products of the aldol condensation of propionaldehyde and isobutyraldehyde.The 2-methyl- and 2,4-dimethylpent-2E-enals were oxidized to the corresponding acids, which were converted into the chlorides and these into the corresponding sec-amyl esters.The geometric purity of the products was shown by their PMR spectra (250 MHz).
- Cheskis, B. A.,Yarutich, A. P.,Lebedeva, K. V.,Moiseenkov, A. M.
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Read Online
- Synthesis method of trans-2-methyl-2-pentenoic acid
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The invention adopts a Reppe synthesis method to prepare 2-methyl-2-pentenoic acid. The method comprises the following steps: firstly, by taking m-pentadiene, carbon monoxide and water as raw materials, and taking precious metal rhodium salt and an organic phosphine ligand as catalysts, preparing a cis-trans isomeric intermediate of 2-methyl-3-pentenoic acid, and then carrying out isomerization reaction on the obtained intermediate product to generate trans-2-methyl-2-pentenoic acid, namely trans strawberry acid.
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Paragraph 0068-0072; 0078-0082
(2021/09/04)
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- Systematic methodology for the development of biocatalytic hydrogen-borrowing cascades: Application to the synthesis of chiral α-substituted carboxylic acids from α-substituted α,β-unsaturated aldehydes
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Ene-reductases (ERs) are flavin dependent enzymes that catalyze the asymmetric reduction of activated carbon-carbon double bonds. In particular, α,β-unsaturated carbonyl compounds (e.g. enals and enones) as well as nitroalkenes are rapidly reduced. Conversely, α,β-unsaturated esters are poorly accepted substrates whereas free carboxylic acids are not converted at all. The only exceptions are α,β-unsaturated diacids, diesters as well as esters bearing an electron-withdrawing group in α- or β-position. Here, we present an alternative approach that has a general applicability for directly obtaining diverse chiral α-substituted carboxylic acids. This approach combines two enzyme classes, namely ERs and aldehyde dehydrogenases (Ald-DHs), in a concurrent reductive-oxidative biocatalytic cascade. This strategy has several advantages as the starting material is an α-substituted α,β-unsaturated aldehyde, a class of compounds extremely reactive for the reduction of the alkene moiety. Furthermore no external hydride source from a sacrificial substrate (e.g. glucose, formate) is required since the hydride for the first reductive step is liberated in the second oxidative step. Such a process is defined as a hydrogen-borrowing cascade. This methodology has wide applicability as it was successfully applied to the synthesis of chiral substituted hydrocinnamic acids, aliphatic acids, heterocycles and even acetylated amino acids with elevated yield, chemo- and stereo-selectivity. A systematic methodology for optimizing the hydrogen-borrowing two-enzyme synthesis of α-chiral substituted carboxylic acids was developed. This systematic methodology has general applicability for the development of diverse hydrogen-borrowing processes that possess the highest atom efficiency and the lowest environmental impact. This journal is
- Knaus, Tanja,Mutti, Francesco G.,Humphreys, Luke D.,Turner, Nicholas J.,Scrutton, Nigel S.
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supporting information
p. 223 - 233
(2015/02/19)
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- The thioesterase domain from the pimaricin and erythromycin biosynthetic pathways can catalyze hydrolysis of simple thioester substrates
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The recombinant polyketide synthase thioesterase domains from the pimaricin and 6-deoxyerythronolide B biosynthetic pathways catalyze hydrolysis of a number of simple N-acetylcysteamine thioester derivatives. This study demonstrates that thioesterases are not highly substrate selective in formation of the acyl-enzyme intermediate, in contrast to non-ribosomal peptide synthase thioesterase domains that show very high specificity for substrate loading. This observation has important implications for the engineering of biosynthetic pathways to produce polyketide products.
- Sharma, Krishna K.,Boddy, Christopher N.
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p. 3034 - 3037
(2008/02/05)
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- Environmentally benign oxidation reaction of aldehydes to their corresponding carboxylic acids using Pd/C with NaBH4 and KOH
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Pd/C catalyst in aqueous methanol with sodium borohydride and potassium hydroxide under the air efficiently oxidized aldehydes to their corresponding carboxylic acids at room temperature. The utilization of room temperature reaction, aqueous methanol solvent, and the open-air conditions make this manipulation very interesting for economic and environmental perspectives.
- Lim, Minkyung,Yoon, Cheol Min,An, Gwangil,Rhee, Hakjune
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p. 3835 - 3839
(2008/02/07)
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- A facile Zn-mediated stereoselective synthesis of (E)- and (Z)-trisubstituted alkenes from Baylis-Hillman adducts in water and its application
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A simple and efficient stereoselective synthesis of (E)- and (Z)-trisubstituted alkenes has been accomplished by treatment of the acetyl derivatives of the Baylis-Hillman adducts with Zn in saturated aq. NH 4C1 solution under reflux. The method has been utilized for the preparation of the two chiral insect pheromones, dominicalure-I and dominicalure-II, of the lesser grain borer Rhyzopertha dominica (F). Copyright
- Das, Biswanath,Chowdhury, Nikhil,Banerjee, Joydeep,Majhi, Anjoy,Mahender, Gurram
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p. 358 - 359
(2007/10/03)
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- A facile one-pot stereoselective synthesis of trisubstituted (E)-2-methylalk-2-enoic acids from unactivated Baylis-Hillman adducts and a simple access to some important insect pheromones
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An efficient one-pot stereoselective synthesis of trisubstituted (E)-2-methylalk-2-enoic acids has been accomplished by treatment of unactivated Baylis-Hillman adducts, 3-hydroxy-2-methylenealkanoates, with Al-NiCl2·6H2O in methanol at room temperature followed by hydrolysis. The method has been applied to the synthesis of three important insect pheromones, (4S,2E)-2,4-dimethyl-2-hexenoic acid, (+)-(S)-manicone and (+)-(S)-normanicone.
- Das, Biswanath,Chowdhury, Nikhil,Banerjee, Joydeep,Majhi, Anjoy
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p. 6615 - 6618
(2007/10/03)
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- Synthetic applications of the Baylis-Hillman reaction: Simple and convenient synthesis of five important insect pheromones
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A simple and convenient synthesis of five important insect pheromones by means of Baylis-Hillman adducts is described, i.e., of (2E,4S)-2,4-dimethylhex- 2-enoic acid (1), a mandibular-gland secretion of the male carpenter ant in the genus Camponotus, of (+)-(S)-manicone (2) and (+)-(S)-normanicone (3), two mandibular-gland constituents of Manica ants, and of (+)-dominicalure-I (6) and (+)-dominicalure-II (7), two aggregation pheromones of the lesser grain borer Rhyzopertha dominion (F). For the first time, the potential of the Baylis-Hillman chemistry for the stereoselective synthesis of trisubstituted olefins was successfully applied to the synthesis of these pheromone compounds.
- Das, Biswanath,Banerjee, Joydeep,Chowdhury, Nikhil,Majhi, Anjoy,Mahender, Gurram
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p. 876 - 883
(2007/10/03)
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- Stereoselective synthesis of (E)-trisubstituted α,β-unsaturated amides and acids
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Potassium alkoxides of N-acyl-oxazolidin-2-one-syn-aldols undergo stereoselective elimination reactions to afford a range of trisubstituted (E)-αβ-unsaturated amides in >95% de, that may be subsequently converted into their corresponding (E)-αβ-unsaturated acids or (E)-αβ-unsaturated oxazolines in good yield. syn-Aldols derived from αβ-unsaturated aldehydes gave their corresponding trisubstituted (E)-αβ-unsaturated-amides with poorer levels of diastereocontrol, whilst there was a similar loss in (E)-selectivity during elimination of syn-aldols derived from chiral aldehydes. These elimination reactions proceed via rearrangement of the potassium alkoxide of the syn-aldol to a 1,3-oxazinane-2,4-dione enolate intermediate that subsequently eliminates carbon dioxide to afford a trisubstituted (E)-αβ-unsaturated amide. The (E)-selectivity observed during the ElcB-type elimination step has been rationalised using a simple conformational model that employs a chair-like transition state to explain the observed stereocontrol. The Royal Society of Chemistry 2005.
- Feuillet, Fred J. P.,Cheeseman, Matt,Mahon, Mary F.,Bull, Steven D.
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p. 2976 - 2989
(2007/10/03)
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- An (E)-selective synthesis of trisubstituted (E)-α, β-unsaturated acid derivatives
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Potassium alkoxides of N-acyloxazolidin-2-one derived synaldolates undergo a novel tandem intramolecular cyclisation elimination reaction to afford trisubstituted (E)-α,β-unsaturated amides in high d.e., which may be converted into their corresponding acids or oxazolines in good yield.
- Feuillet, Fred J. P.,Robinson, Diane E. J. E.,Bull, Steven D.
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p. 2184 - 2185
(2007/10/03)
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- Alkylation of lithium dienediolates of butenoic acids. Regioselectivity effects of structure and leaving group of the alkylating agent
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Regioselectivity of alkylation of but-2-enoic acids I and 2 by alkyl halides strongly depends on the reactivity of the electrophile. High α selectivity results for saturated alkyl halides, whereas poor α-selectivity is obtained for highly reactive allyl and benzyl halides. For reactive alkylating halides selectivity is partly governed by the ion pairing aggregates of the dienediolates. Lithium bromide and the carboxylate generated in the ongoing reaction cause opposite effects on regioselectivity.
- Aurell, Maria J.,Gil, Salvador,Mestres, Ramon,Parra, Margarita,Parra, Lilian
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p. 4357 - 4366
(2007/10/03)
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- Stereoselective synthesis of dominicalure 1 and 2: Components of aggregation pheromone from male lesser grain borer Rhyzopertha dominica (F.)
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Dominicalure 1 (9a) and dominicalure 2 (9b), were synthesized by esterification of α,β-unsaturated acids 4a and 4b with (5)-(+)-2-pentanol (8). The key step was the asymmetric reduction of 3-penten-2-one (5) to give the chiral intermediate 6, which, upon diimide reduction, DNB derivatization, recrystallization, and hydrolysis, yielded 8 in 63% ee. Acids 4a and 4b were prepared in a simple and efficient three-step synthesis with an overall yield of 54% and 62%, respectively, in stereoisomerically pure form.
- Razkin,Gil,Gonzalez
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p. 673 - 680
(2007/10/03)
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- Structure-activity relationships of unsaturated analogues of valproic acid
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The principal metabolite of valproic acid (VPA), 2-ene VPA, appears to share most of VPA's pharmacological and therapeutic properties while lacking its hepatotoxicity and teratogenicity, thus making it a useful lead compound for the development of safer antiepileptic drugs. Analogues of 2-ene VPA were evaluated for anticonvulsant activity in mice using the subcutaneous pentylenetetrazole test. Cyclooctylideneacetic acid exhibited a potency markedly exceeding that of VPA itself with only modest levels of sedation. Potency, as either ED50 or brain concentration, was highly correlated (r > 0.85) with volume and lipophilicity rather than with one of the shape parameters calculated by molecular modeling techniques, arguing against the existence of a specific receptor site. Instead, a role for the plasma membrane in mediating the anticonvulsant effect is suggested.
- Palaty,Abbott
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p. 3398 - 3406
(2007/10/02)
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- Synthetic application of alkyl (E)-2-tributylstannyl-2-alkenoates: Selective synthesis of (S)-1-methylbutyl (E)-2-methyl-2-pentenoate, an aggregation pheromone component of Rhyzopertha dominica and Prostephanus truncatus
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Stereoisomerically pure (S)-1-methylbutyl (E)-2-methyl-2-pentenoate (dominicalure-1), (S)(E)-11, an aggregation pheromone component for the lesser and the greater grain borers, has been efficiently synthesized from the main product of the palladium-catalyzed reaction between ethyl 2-pentynoate, 1a, and Bu3SnH, i.e. ethyl (E)-2-tributylstannyl-2-pentenoate, (E)-2a.
- Rossi,Carpita,Cossi
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p. 143 - 152
(2007/10/02)
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- Synthesis of α-Methylene β-Lactones, Novel Heterocycles
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Triphenylphosphin deoxygenation of β-alkyl-, β,β-dialkyl-, and β,β-spirocycloalkyl-substituted α-methylene-β-peroxy lactones 3a-k, which are readily available by photooxygenation of the corresponding α,β-unsaturated carboxylic acids 1, and cyclization of the resulting α-methylene-β-hydroperoxy acids 2 constitute a convenient method for the preparation of a variety of α-methylene β-lactones 5.Alternatively, the α-methylene-β-hydroxycarboxylic acids 4 can be directly cyclized by benzenesulfonyl chloride in pyridine into these novel four membered ring heterocycles 5.
- Adam, Waldemar,Albert, Rainer,Grau, Nuria Dachs,Hasemann, Ludwig,Nestler, Bernd,et al.
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p. 5778 - 5781
(2007/10/02)
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- Alkyl esters of 1-alkanoyl cycloalkanols and organoleptic uses thereof
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Described is a process for preparing several substituted or unsubstituted cycloalkyl acyl alkanoates defined according to the generic structure: STR1 wherein R1 and R2 taken together complete a cycloalkyl moiety or methyl, dimethyl or trimethyl substituted cycloalkyl moiety containing five or six carbon atoms in the ring and wherein R3 is C1 -C3 lower alkyl and R4 is methyl or hydrogen by reacting a compound having the generic structure: STR2 in an aqueous silver-ion containing solution having a weakly acidic pH at elevated temperatures. The compounds so produced are useful for their organoleptic properties in consumable materials, such as foodstuffs, foodstuff flavorants, chewing gums, chewing gum flavorants, toothpastes, toothpaste flavorants, medicinal products, medicinal product flavorants, chewing tobaccos, chewing tobacco flavorants, smoking tobaccos, smoking tobacco flavorants, perfume compositions, perfumed articles, such as cationic, anionic, nonionic and zwitterionic detergents, fabric softener compositions, drier-added fabric softener articles, textile sizing agents and optical brighteners for textiles as well as colognes.
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- Acid-Catalyzed Rearrangements of Vinylketene/Cyclopentadiene Adducts
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Vier Alkyl-vinylketene (7b-e), in situ durch 1,4-Eliminierung von HCl aus den entsprechenden α,β-ungesaettigten Acylchloriden hergestellt, wurden mit Cyclopentadien umgesetzt.Durch -Cycloaddition entstanden 7-alkyl-7-vinylsubstituierte Bicyclohept-2-en-6-one 8/9.Das Stereoisomerenverhaeltnis 8:9 haengt von der relativen Groesse der Ketensubstituenten ab.Die Vinylketen/Cyclopentadien-Addukte 8/9 enthalten ein α-Vinylcyclobutanon-, ein Cope- und (bei 8f) ein Allylchlorid-System.Unter dem Einfluss von Saeuren (meistens BF3-Aetherat) wurden bei 8/9 vier verschiedene Typen von Umlagerungsreaktionen beobachtet, naemlich, je nach dem Substitutionsmuster: -Alkyl-Wanderung zu Bicyclononadienonen 12, -Acyl-Wanderung zu Bicyclooctenonen 13, -Cope-Umlagerung zu Bicyclononadienonen 14 oder -Halogen-Wanderung zu 7-Alkylidenbicycloheptenonen 15.Die -Alkyl- und -Acyl-Wanderungen konkurrieren mit der Cope-Umlagerung, wobei auch die Konfiguration an C(7) der Vinylketen/Cyclopentadien-Addukte (8 bzw.9) und das Loesungsmittel eine Rolle spielen koennen.
- Huston, Rima,Rey, Max,Dreiding, Andre S.
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p. 1563 - 1575
(2007/10/02)
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