RESUMO
In this contribution, we report chemoenzymatic bromodecarboxylation (Hunsdiecker-type) of α,ß-unsaturated carboxylic acids. The extraordinarily robust chloroperoxidase from Curvularia inaequalis (CiVCPO) generated hypobromite from H2O2 and bromide, which then spontaneously reacted with a broad range of unsaturated carboxylic acids and yielded the corresponding vinyl bromide products. Selectivity issues arising from the (here undesired) addition of water to the intermediate bromonium ion could be solved by reaction medium engineering. The vinyl bromides so obtained could be used as starting materials for a range of cross-coupling and pericyclic reactions.
RESUMO
The synthesis of aldehydes from carboxylic acids has long been a challenge in chemistry. In contrast to the harsh chemically driven reduction, enzymes such as carboxylic acid reductases (CARs) are considered appealing biocatalysts for aldehyde production. Although structures of single- and didomains of microbial CARs have been reported, to date no full-length protein structure has been elucidated. In this study, we aimed to obtain structural and functional information regarding the reductase (R) domain of a CAR from the fungus Neurospora crassa (Nc). The NcCAR R-domain revealed activity for N-acetylcysteamine thioester (S-(2-acetamidoethyl) benzothioate), which mimics the phosphopantetheinylacyl-intermediate and can be anticipated as the minimal substrate for thioester reduction by CARs. The determined crystal structure of the NcCAR R-domain reveals a tunnel that putatively harbors the phosphopantetheinylacyl-intermediate, which is in good agreement with docking experiments performed with the minimal substrate. In vitro studies were performed with this highly purified R-domain and NADPH, demonstrating carbonyl reduction activity. The R-domain was able to accept not only a simple aromatic ketone but also benzaldehyde and octanal, which are typically considered to be the final product of carboxylic acid reduction by CAR. Also, the full-length NcCAR reduced aldehydes to primary alcohols. In conclusion, aldehyde overreduction can no longer be attributed exclusively to the host background.
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Aromatic hydroxylation reactions catalyzed by heme-thiolate enzymes proceed via an epoxide intermediate. These aromatic epoxides could be valuable building blocks for organic synthesis giving access to a range of chiral trans-disubstituted cyclohexadiene synthons. Here, we show that naphthalene epoxides generated by fungal peroxygenases can be subjected to nucleophilic ring opening, yielding non-racemic trans-disubstituted cyclohexadiene derivates, which in turn can be used for further chemical transformations. This approach may represent a promising shortcut for the synthesis of natural products and APIs.
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En route to a bio-based chemical industry, the conversion of fatty acids into building blocks is of particular interest. Enzymatic routes, occurring under mild conditions and excelling by intrinsic selectivity, are particularly attractive. Here we report photoenzymatic cascade reactions to transform unsaturated fatty acids into enantiomerically pure secondary fatty alcohols. In a first step the C=C-double bond is stereoselectively hydrated using oleate hydratases from Lactobacillus reuteri or Stenotrophomonas maltophilia. Also, dihydroxylation mediated by the 5,8-diol synthase from Aspergillus nidulans is demonstrated. The second step comprises decarboxylation of the intermediate hydroxy acids by the photoactivated decarboxylase from Chlorella variabilis NC64A. A broad range of (poly)unsaturated fatty acids can be transformed into enantiomerically pure fatty alcohols in a simple one-pot approach.
Assuntos
Ácidos Graxos Insaturados/química , Ácidos Graxos Insaturados/metabolismo , Álcoois Graxos/química , Álcoois Graxos/metabolismo , Produtos Biológicos/química , Produtos Biológicos/metabolismo , Limosilactobacillus reuteri/metabolismo , Stenotrophomonas maltophilia/metabolismo , Especificidade por SubstratoRESUMO
The scale-up of chemoenzymatic bromolactonization to 100 g scale is presented, together with an identification of current limitations. The preparative-scale reaction also allowed for meaningful mass balances identifying current bottlenecks of the chemoenzymatic reaction.
RESUMO
Invited for this month's cover is the group of Prof.â Dr. Frank Hollmann at Delft University of Technology in the Netherlands. The Front Cover shows the vanadium-dependent haloperoxidase from the marine organism Curcuvaria inaequalis, which efficiently activates halides as hypohalites that can then initiate spontaneous halo-lactonization and halo-etherification reactions. The Communication itself is available at 10.1002/cssc.201902240.
RESUMO
A chemoenzymatic method for the halocyclization of unsaturated alcohols and acids by using the robust V-dependent chloroperoxidase from Curvularia inaequalis (CiVCPO) as catalyst has been developed for the in situ generation of hypohalites. A broad range of halolactones and cyclic haloethers are formed with excellent performance of the biocatalyst.
RESUMO
The complex amino acid (l-threo)-3-[3-[4-(trifluoromethyl)benzoylamino]benzyloxy]aspartate (l-TFB-TBOA) and its derivatives are privileged compounds for studying the roles of excitatory amino acid transporters (EAATs) in regulation of glutamatergic neurotransmission, animal behavior, and in the pathogenesis of neurological diseases. The wide-spread use of l-TFB-TBOA stems from its high potency of EAAT inhibition and the lack of off-target binding to glutamate receptors. However, one of the main challenges in the evaluation of l-TFB-TBOA and its derivatives is the laborious synthesis of these compounds in stereoisomerically pure form. Here, we report an efficient and step-economic chemoenzymatic route that gives access to enantio- and diastereopure l-TFB-TBOA and its derivatives at multigram scale.
Assuntos
Sistema X-AG de Transporte de Aminoácidos/antagonistas & inibidores , Aminoácidos/síntese química , Aminoácidos/metabolismo , Ácido Aspártico/análogos & derivados , Enzimas/metabolismo , Aminoácidos/química , Ácido Aspártico/síntese química , Ácido Aspártico/química , Ácido Aspártico/metabolismo , Estrutura Molecular , EstereoisomerismoRESUMO
Pyrazolidine-3,5-diones and their derivatives exhibit a wide range of biological activities. Seeking to explore the effect of combining a hydrocarbyl ring substituent, as present in sulfinpyrazone (used to treat gout), with a chlorinated aryl ring, as present in muzolimine (a diuretic), we explored the reaction between 1-phenylpyrazolidine-3,5-dione and 4-chlorobenzaldehyde under mildly basic conditions in the expectation of producing the simple condensation product 4-(4-chlorobenzylidene)-1-phenylpyrazolidine-3,5-dione. However, the reaction product proved to be meso-(E,E)-1,1'-[1,2-bis(4-chlorophenyl)ethane-1,2-diyl]bis(phenyldiazene), C26H20Cl2N4, and a tentative mechanism is proposed. Crystallization from ethanol produces two concomitant polymorphs, i.e. a triclinic form, (I), in the space group P-1, and a monoclinic form, (II), in the space group C2/c. In both polymorphs, the molecules lie across centres of inversion, but in (II), the molecules are subject to whole-molecule disorder equivalent to configurational disorder with occupancies of 0.6021â (19) and 0.3979â (19). There are no hydrogen bonds in the crystal structure of polymorph (I), but the molecules of polymorph (II) are linked by C-H...π(arene) hydrogen bonds into complex chains, which are further linked into sheets by C-H...N interactions.
Assuntos
Iminas/síntese química , Fenômenos Biológicos , Cristalização , Cristalografia por Raios X , Ligação de Hidrogênio , Iminas/química , Modelos Moleculares , Estrutura MolecularRESUMO
The wide diversity of applications of thiosemicarbazones and bis(thiosemicarbazones) has seen them used as anticancer and antitubercular agents, and as ligands in metal complexes designed to act as site-specific radiopharmaceuticals. Molecules of 1,1'-({[(ethane-1,2-diyl)dioxy](1,2-phenylene)}bis(methanylylidene))bis(thiosemicarbazide) {alternative name: 2,2'-[ethane-1,2-diylbis(oxy)]dibenzaldehyde bis(thiosemicarbazide)}, C18H20N6O2S2, (I), lie across twofold rotation axes in the space group C2/c, with an O-C-C-O torsion angle of -59.62â (13)° and a trans-planar arrangement of the thiosemicarbazide fragments relative to the adjacent aryl rings. The molecules of (I) are linked by N-H...S hydrogen bonds to form sheets containing R(2)4(38) rings and two types of R(2)2(8) ring. In the N,N-dimethylformamide disolvate, C18H20N6O2S2·2C3H7NO, (II), the independent molecular components all lie in general positions, but one of the solvent molecules is disordered over two sets of atomic sites having occupancies of 0.839â (3) and 0.161â (3). The O-C-C-O torsion angle in the ArOCH2CH2OAr component is -75.91â (14)° and the independent thiosemicarbazide fragments both adopt a cis-planar arrangement relative to the adjacent aryl rings. The ArOCH2CH2OAr components in (II) are linked by N-H...S hydrogen bonds to form deeply puckered sheets containing R(2)2(8), R(2)4(8) and two types of R(2)2(38) rings, and which contain cavities which accommodate all of the solvent molecules in the interior of the sheets. Comparisons are made with some related compounds.
Assuntos
Formamidas/química , Formamidas/farmacologia , Solventes/química , Tiossemicarbazonas/química , Tiossemicarbazonas/farmacologia , Cristalografia por Raios X , Ligantes , Conformação MolecularRESUMO
In the title compound, C20H14N2O2, the hy-droxy-benzene ring is almost perpendicular to the mean plane of the naphthalene ring system, making a dihedral angle of 85.56â (4)°. The 4H-pyran ring fused with the naphthalene ring system has a flattened boat conformation. In the crystal, O-Hâ¯N and N-Hâ¯O hydrogen bonds link the mol-ecules into a supra-molecular layer in the bc plane; N-Hâ¯π inter-actions also contribute to this arrangement. The layers are linked by weak by C-Hâ¯π and π-π [inter-centroid separation = 3.8713â (7)â Å] inter-actions.
RESUMO
In the title compound, C16H12N2O3, the chromene ring system is nearly planar [maximum deviation from the mean plane = 0.057â (1)â Å], and is almost perpendicular to the benzene ring, with a dihedral angle of 85.29â (5)°. In the crystal, mol-ecules are linked by classical N-Hâ¯O, O-Hâ¯O and O-Hâ¯N hydrogen bonds, and weak C-Hâ¯O hydrogen bonds, forming a three-dimensional supra-molecular network. Furthermore, a weak π-π stacking inter-action is observed; the centroid-to-centroid distance is 3.7260â (7)â Å.
RESUMO
In the title compound, C21H16N2O2, the meth-oxy-benzene ring is almost perpendicular to the mean plane of the naphthalene ring system, making a dihedral angle of 83.62â (5)°. The 4H-pyran ring fused with the naphthalene ring system is almost planar [maximum deviation = 0.033â (1)â Å]. In the crystal, mol-ecules are linked into inversion dimers by pairs of N-Hâ¯N hydrogen bonds. N-Hâ¯O hydrogen bonds connect the dimers, forming a helical supra-molecular chain along the a-axis direction. The crystal packing also features C-Hâ¯π inter-actions.
RESUMO
In the title compound, C20H13ClN2O, the chloro-benzene ring is almost perpendicular to the mean plane of the naphthalene ring system, making a dihedral angle of 81.26â (8)°. The 4H-pyran ring fused with the naphthalene ring system has a flattened boat conformation. In the crystal, N-Hâ¯N hydrogen bonds generate chains along the b-axis direction. Further N-Hâ¯N hydrogen bonds link these chains into sheets parallel to (010). The crystal packing also features C-Hâ¯π inter-actions. The crystal studied was an inversion twin with a 0.557â (16):0.443â (16) domain ratio.
RESUMO
In the title compound, C20H14N2O, the plane of the phenyl ring is almost normal to that of the naphthalene ring system, forming a dihedral angle of 83.15â (8)°. The 4H-pyran ring fused with the naphthalene ring system has a flattened boat conformation. In the crystal, mol-ecules are linked by pairs of N-Hâ¯N hydrogen bonds, forming inversion dimers with an R 2 (2)(12) ring motif. The dimers are connected by C-Hâ¯π inter-actions, forming supra-molecular chains along [010].
RESUMO
In the title compound, C18H17NO4, the dihedral angle between the phenyl ring and the fused six-membered ring is 77.65â (4)°. The conformation of the mol-ecule is determined in part by an intra-molecular N-Hâ¯O hydrogen bond between the amino H atom and the carbonyl O atom, forming an S(6) motif. In the crystal, mol-ecules are linked into N-Hâ¯O hydrogen-bonded inversion dimers which are then connected into chains along [001], forming a two-dimensional network parallel to (100) via O-Hâ¯O hydrogen bonds. C-Hâ¯O interactions further contribute to the crystal stability. The ethyl group is disordered over two sets of sites in a 0.801â (5):0.199â (5) ratio.
RESUMO
The title mol-ecule, C19H22N6O2S2, has crystallographically imposed C 2 symmetry, with the central C atom lying on the rotation axis. The O-C-C-C torsion angle for the central chain is -59.22â (16)° and the dihedral angle between the planes of the benzene rings is 75.20â (7)°. In the crystal, N-Hâ¯O and N-Hâ¯S inter-actions link the mol-ecules, forming a three-dimensional network encompassing channels running parallel to the c axis, which account for about 20% of the unit-cell volume. The contribution to the scattering from the highly disordered solvent mol-ecules in these channels was removed with the SQUEEZE routine [Spek (2015). Acta Cryst. C71, 9-18] in PLATON. The stated crystal data for M r, µ etc. do not take these into account.
RESUMO
In the title compound, C16H12N2O3, the 2H-chromene moiety is essentially planar, with an r.m.s. deviation of the nine constituent atoms from the mean plane of 0.0093â Å, and makes a dihedral angle of 76.84â (3)° with the pendant phenyl ring. An intra-molecular N-Hâ¯O hydrogen bond helps to determine the conformation of the side chain. In the crystal, N-Hâ¯O and N-Hâ¯N hydrogen bonds link the mol-ecules, forming [100] chains.
RESUMO
In the title compound, C21H16N2O2, the naphthalene fragment is twisted slightly, as indicated by the dihedral angle of 3.2â (2)° between the two six-membered rings. The pendant 4-meth-oxy-phenyl ring makes a dihedral angle of 86.08â (6)° with the central six-membered ring of the 4H-benzo[g]chromene ring system. In the crystal, mol-ecules are linked by pairs of N-Hâ¯N hydrogen bonds, forming inversion dimers which are linked into chains propagating in the b-axis direction by N-Hâ¯O hydrogen bonds.
RESUMO
In the title compound, C10H6BrNO3S, the dihedral angle between the thia-zolidine ring (r.m.s. deviation = 0.014â Å) and the benzene ring is 5.78â (14)°. The S atom of the heterocyclic ring is syn to the OH group attached to the benzene ring. In the crystal, inversion dimers linked by pairs of N-Hâ¯O hydrogen bonds generate R 2 (2)(8) loops. The dimers are linked into [001] ribbons by pairwise O-Hâ¯O hydrogen bonds with R 2 (2)(18) motifs. There are no short contacts involving the Br atom.