- Ketonization of 2-hydroxy-2,4-pentadienoate by 4-oxalocrotonate tautomerase: Implications for the stereochemical course and the mechanism
-
4-Oxalocrotonate tautomerase (EC 5.3.2-; 4-OT), an enzyme involved in the bacterial degradation of catechol to intermediates in the Krebs cycle, catalyzes the ketonization of 2-hydroxymuconate (1) to the α,β-unsaturated ketone (E)-2-oxo-3-hexenedioate (2). Kinetic studies on 4-OT suggest that the enzyme is an isomerase and catalyzes the transformation of (E)-2-oxo-4-hexenedioate (3) to 2 through the intermediacy of 1. Isomerases can proceed by either a "one-base" or a "two-base" mechanism. The overall stereochemical course of an isomerase reaction can be used to distinguish between these two mechanisms. The stereochemical analysis of the 4-OT reaction presents a challenge because the proposed substrate, 3, cannot be synthesized or isolated. This complication is circumvented by utilizing strategies based on the expected stereospecific partitioning of 1 and related dienols in 2H2O. It was previously determined that 4-OT ketonizes 1 to (5S)-[5-2H]2. Because it was not possible to obtain sufficient quantities of [3-2H]3 for stereochemical analysis, an alternate substrate for 4-OT, 2-hydroxy-2,4-pentadienoate (4), was used in order to determine the stereochemistry of deuterium incorporation at the 3-position. The dienol 4 is ketonized rapidly by 4-OT to the β,γ-unsaturated ketone 2-oxo-4-pentenoate (5) before a much slower conversion to its α,β-isomer, 2-oxo-3-pentenoate (6). This behavior allows for the accumulation of 5 in solution. In order to assign the stereochemistry, the 4-OT-catalyzed ketonization of 4 was performed in 2H2O. The product, [3-2H]5, was trapped with NaBH4, processed to [3-2H]malate by chemical and enzymatic degradative procedures, and analyzed by 1H NMR spectroscopy. It was concluded that 4-OT ketonizes 4 stereoselectively to (3R)-2-oxo-[3-2H]-4-pentenoate. This result and the previous stereochemical finding indicate that the isomerization of 3 to 2 is predominantly a suprafacial process suggesting that 4-OT proceeds by a one-base mechanism.
- Lian, Huiling,Whitman, Christian P.
-
-
Read Online
- One-Shot Intrablock Cross-Linking of Linear Diblock Copolymer to Realize Janus-Shaped Single-Chain Nanoparticles
-
Developing an efficient and versatile process to transform a single linear polymer chain into a shape-defined nanoobject is a major challenge in the fields of chemistry and nanotechnology to replicate sophisticated biological functions of proteins and nucleic acids in a synthetic polymer system. In this study, we performed one-shot intrablock cross-linking of linear block copolymers (BCPs) to realize single-chain nanoparticles (SCNPs) with two chemically compartmentalized domains (Janus-shaped SCNPs). Detailed structural characterizations of the Janus-shaped SCNP composed of polystyrene-block-poly(glycolic acid) revealed its compactly folded conformation and compartmentalized block localization, similar to the self-folded tertiary structures of natural proteins. Versatility of the one-shot intrablock cross-linking was demonstrated using several different BCP precursors. In addition, the Janus-shaped SCNP produce miniscule microphase-separated structures.
- Isono, Takuya,Kaizawa, Noya,Ree, Brian J.,Satoh, Toshifumi,Tajima, Kenji,Watanabe, Kodai,Yamamoto, Takuya
-
-
Read Online
- Generation of a Heteropolycyclic and sp3-Rich Scaffold for Library Synthesis from a Highly Diastereoselective Petasis/Diels–Alder and ROM–RCM Reaction Sequence
-
Efficient access to diverse screening compounds with desirable, lead-like properties can be a bottleneck in early drug discovery and chemical biology. Herein we present an efficient, rapid route to three structurally distinct classes of compounds (A–C) from a single precursor, which in turn is available through a one-pot Petasis 3-component reaction/Diels–Alder cascade reaction. We demonstrate the versatility of the approach through the synthesis of 35 exemplary compounds from the three classes, as well as by the production of 2188 final compounds, which have been included in the Joint European Compound Library of the European Lead Factory.
- Flagstad, Thomas,Azevedo, Carlos M. G.,Troelsen, Nikolaj S.,Min, Geanna K.,Macé, Yohan,Willaume, Anthony,Guilleux, Rachel,Velay, Mélanie,Bonnet, Karine,Morgentin, Remy,Nielsen, Thomas E.,Clausen, Mads H.
-
p. 1061 - 1076
(2019/01/04)
-
- Diastereoselective synthesis of novel heterocyclic scaffolds through tandem Petasis 3-component/intramolecular Diels-Alder and ROM-RCM reactions
-
A high-yielding, stereoselective and extraordinarily complexity-generating Petasis 3-component/intramolecular Diels-Alder reaction has been developed. In combination with ROM-RCM, rapid access to complex sp3-rich heterocyclic scaffolds amenable
- Ishoey, Mette,Petersen, Rico G.,Petersen, Michael ?.,Wu, Peng,Clausen, Mads H.,Nielsen, Thomas E.
-
supporting information
p. 9410 - 9413
(2017/08/29)
-
- MICROORGANISMS FOR PRODUCING 4C-5C COMPOUNDS WITH UNSATURATION AND METHODS RELATED THERETO
-
The invention provides a non-naturally occurring microbial organism having a butadiene, crotyl alcohol, 2,4-pentadienoate, 3-buten-2-ol, or 3-buten-1-ol, pathway. The microbial organism contains at least one exogenous nucleic acid encoding an enzyme in a pathway. The invention additionally provides a method for producing butadiene, crotyl alcohol, 2,4-pentadienoate, 3-buten-2-ol, or 3-buten-1-ol,. The method can include culturing a butadiene, crotyl alcohol, 2,4-pentadienoate, 3-buten-2-ol, or 3-buten-1-ol-producing microbial organism, where the microbial organism expresses at least one exogenous nucleic acid encoding a pathway enzyme in a sufficient amount, and under conditions and for a sufficient period of time to produce butadiene, crotyl alcohol, 2,4-pentadienoate, 3-buten-2-ol, or 3-buten-1-ol.
- -
-
-
- Electrochemical allylation of carbonyl compounds in aqueous electrolyte catalyzed by zinc
-
A highly efficient electroallylation of carbonyl compounds in aqueous electrolyte in a divided cell with a catalytic amount of zinc consumption is reported.
- Huang, Jing-Mei,Ren, Hai-Rui
-
supporting information; experimental part
p. 2286 - 2288
(2010/07/08)
-
- Zn-mediated electrochemical allylation of aldehydes in aqueous ammonia
-
An efficient electrosynthesis of homoallylic alcohols from allylic bromides and aldehydes in aqueous ammonia is achieved in an undivided cell fitted with a pair of zinc electrodes.
- Huang, Jing-Mei,Dong, Yi
-
supporting information; experimental part
p. 3943 - 3945
(2009/12/25)
-
- Efficient allylation of aldehydes promoted by carboxylic acids
-
A variety of carboxylic acids have been screened for mediating the allylation of aldehydes with allytributyltin in different solvents. A novel, general, and practical method of allylation of aldehydes promoted by carboxylic acids under mild reaction condi
- Li, Gui-Long,Zhao, Gang
-
p. 4272 - 4278
(2007/10/03)
-
- Highly enantioselective sequential Claisen-Ireland/metathesis: Synthesis of cycloalkenes bearing two contiguous highly functionalized asymmetric centres
-
A sequence of two reactions, consisting of a highly stereoselective silylated ketene acetal Claisen-Ireland rearrangement followed by a ring closing metathesis, gave a stereocontrolled access to various carbocycles.
- Francais, Antoine,Bedel, Olivier,Picoul, Willy,Meddour, Abdelkrim,Courtieu, Jacques,Haudrechy, Arnaud
-
p. 1141 - 1155
(2007/10/03)
-
- Regio- and stereochemical aspects in synthesis of 2-allyl derivatives of glycolic, mandelic and lactic acids and their iodocyclisations to 3-hydroxy-3,4-dihydrofuran-2(5H)-ones
-
Glyoxalic, phenylglyoxalic and pyruvic acids 1a-c undergo regio- and diastereoselective indium mediated allylations with allyl and cinnamyl bromides and ethyl 4-bromocrotonate to provide respective 2-allyl-, 2-(1-phenylallyl)- and 2-[(1-ethoxycarbonyl)all
- Kaur, Pervinder,Singh, Palwinder,Kumar, Subodh
-
p. 8231 - 8240
(2007/10/03)
-
- Direct synthesis of unprotected α-amino acids via allylation of hydroxyglycine
-
Hydroxyglycine, the ammonia adduct of glyoxylic acid, was found to react with various allylboronates in the presence of triethylamine in methanol to give unprotected α-amino acids directly with high stereoselectivity. For instance, the reactions with (E)- and (Z)-crotylboronates afforded the corresponding anti- and syn-crotylated products (isoleucine and alloisoleucine after hydrogenation) with high diastereoselectivity, respectively. Interestingly, it was found that isomerization of the products (γ-adducts to α-adducts) occurred under the reaction conditions in some cases. Control experiments have suggested that the isomerization took place via 2-aza (or azonia) Cope rearrangement of imines derived from γ-adducts and glyoxylic acid.
- Sugiura, Masaharu,Mori, Chieko,Hirano, Keiichi,Kobayashi, Shu
-
p. 937 - 942
(2007/10/03)
-
- InCl3-Promoted Allylation of Aldehydes in Ionic Liquid: Scope and Enantioselectivity Studies
-
Indium trichloride was successfully applied to allylation reaction of aldehydes using allytributyltin in ionic liquids. This accelerated catalytic system afforded the allylated products of various aldehydes in moderate to high yields. Preliminary studies
- Lu, Jun,Ji, Shun-Jun,Qian, Rong,Chen, Jian-Ping,Liu, Yu,Loh, Teck-Peng
-
p. 534 - 536
(2007/10/03)
-
- A tin hydride designed to facilitate removal of tin species from products of stannane-mediated radical reactions
-
The stannane 1, which is simple to prepare, behaves like the conventional reagents Bu3SnH and Ph3SnH in standard free radical reactions, but with the special characteristic that the tin-containing byproducts are easily and very largely removed by mild hydrolysis (LiOH-water-THF or TsOH-water-THF), which converts them into base-soluble (aqueous NaHCO3) materials. The performance of stannane 1 was evaluated for a range of radical reactions involving halides, selenides, Barton-McCombie deoxygenation, and enyne cyclization. In several cases the effectiveness of the workup procedure in removing tin species was monitored by 1H NMR.
- Clive, Derrick L. J.,Wang, Jian
-
p. 1192 - 1198
(2007/10/03)
-
- The efficient allylations of 2-oxocarboxylic acids. Synthesis of 2-allyl derivatives of 2-hydroxycarboxylic acids
-
2-Oxocarboxylic acids or their sodium salts undergo indium-mediated allylation with allyl bromide cinnamyl bromide and ethyl 4- bromocrotonate to provide the corresponding 2-allyl derivatives of glycolic lactic mandelic and malic acids. In the case of rea
- Kumar, Subodh,Kaur, Pervinder,Chimni, Swapandeep Singh
-
p. 573 - 574
(2007/10/03)
-
- Trifluoromethane sulphonic acid: A Bronsted acid catalyst for the addition of allyltributylstannanes to carbonyl compounds in water
-
Trifluoromethane sulphonic acid catalyses the addition of allyltributylstannane to carbonyl compounds in water to give the corresponding homoallylic alcohols in high yields.
- Loh, Teck-Peng,Xu, Jia
-
p. 2431 - 2434
(2007/10/03)
-
- Fructose 1,6-bisphosphate aldolase from Staphylococcus carnosus: Overexpression, structure prediction, stereoselectivity, and application in the synthesis of bicyclic sugars
-
The gene for the fructose 1,6-bisphosphate aldolase from Staphylococcus carnosus (FruA(sca)) was subcloned for overexpression in Escherichia coli using the expression vector pKK223-3. An efficient, single-step purification by DEAE ion-exchange chromatography furnished the recombinant enzyme ready for synthetic applications. Sequence analysis indicated that FruA(sca) shares the overall α/β-barrel structure and most of the active site residues with the structurally well-defined FruA catalyst from rabbit muscle which signaled its functional equivalence for synthetic applications. A preparative study with generic aliphatic and hydroxylated aldehydes indeed confirmed a high level of stereoselectivity for both newly created asymmetric centers, and suggested a kinetic enantioselectivity for anionically charged 3- hydroxyaldehydes. In fact, the monomeric FruA(sca) was found to tolerate even the presence of highly reactive glutardialdehyde derivatives, which otherwise rapidly denature the rabbit muscle enzyme, and to allow their stereoselective conversion to bicyclic sugars.
- Zannetti, Maria Teresa,Walter, Christiane,Knorst, Marion,Fessner, Wolf-Dieter
-
p. 1882 - 1890
(2007/10/03)
-
- A Grignard-Type Addition of Allyl Unit to Carbonyl Compounds Containing a Carboxyl Group by Using BiCl3-Zn(0)-Allyl Bromide
-
In the presence of BiCl3-Zn(0), nearly equimolar amounts of allyl bromide reacted with carbonyl compounds containing a carboxyl group to afford the corresponding homoallylic alcohols having a carboxyl group or the intramolecular dehydrated lact
- Wada, Makoto,Honna, Munckazu,Kuramoto, Yoshihiro,Miyoshi, Norikazu
-
p. 2265 - 2267
(2007/10/03)
-
- ASYMMETRIC WITTIG SIGMATROPIC REARRANGEMENT INVOLVING A CHIRAL AZAENOLATE AS THE MIGRATING TERMINUS. A SIMPLE SYNTHESIS OF (+)-VERRUCARINOLACTONE
-
The diastereo- and/or enantioselection are described in the title rearrangement of the chiral 2-(2-alkenyloxy)methyl 2-oxazolines which eventually provides optically active α-hydroxy γ,δ-unsaturated esters and (+)-verrucarinolactone.
- Mikami, Koichi,Fujimoto, Katsuhiko,Kasuga, Takashi,Nakai, Takeshi
-
p. 6011 - 6014
(2007/10/02)
-