Browse
Submit Data
Databases
API
Help

Dataset Information

26 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Synthesis of γ-Hydroxy-α-amino Acid Derivatives by Enzymatic Tandem Aldol Addition-Transamination Reactions.

ABSTRACT: Three enzymatic routes toward γ-hydroxy-α-amino acids by tandem aldol addition-transamination one-pot two-step reactions are reported. The approaches feature an enantioselective aldol addition of pyruvate to various nonaromatic aldehydes catalyzed by trans-o-hydroxybenzylidene pyruvate hydratase-aldolase (HBPA) from Pseudomonas putida. This affords chiral 4-hydroxy-2-oxo acids, which were subsequently enantioselectively aminated using S-selective transaminases. Three transamination processes were investigated involving different amine donors and transaminases: (i) l-Ala as an amine donor with pyruvate recycling, (ii) a benzylamine donor using benzaldehyde lyase from Pseudomonas fluorescens Biovar I (BAL) to transform the benzaldehyde formed into benzoin, minimizing equilibrium limitations, and (iii) l-Glu as an amine donor with a double cascade comprising branched-chain α-amino acid aminotransferase (BCAT) and aspartate amino transferase (AspAT), both from E. coli, using l-Asp as a substrate to regenerate l-Glu. The γ-hydroxy-α-amino acids thus obtained were transformed into chiral α-amino-γ-butyrolactones, structural motifs found in many biologically active compounds and valuable intermediates for the synthesis of pharmaceutical agents.

SUBMITTER: Moreno CJ

PROVIDER: S-EPMC8482765 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Biocatalytic Synthesis of Homochiral 2-Hydroxy-4-butyrolactone Derivatives by Tandem Aldol Addition and Carbonyl Reduction.

Project description:Chiral 2-hydroxy acids and 2-hydroxy-4-butyrolactone derivatives are structural motifs often found in fine and commodity chemicals. Here, we report a tandem biocatalytic stereodivergent route for the preparation of these compounds using three stereoselective aldolases and two stereocomplementary ketoreductases using simple and achiral starting materials. The strategy comprises (i) aldol addition reaction of 2-oxoacids to aldehydes using two aldolases from E. coli, 3-methyl-2-oxobutanoate hydroxymethyltransferase (KPHMT Ecoli ), 2-keto-3-deoxy-l-rhamnonate aldolase (YfaU Ecoli ), and trans-o-hydroxybenzylidene pyruvate hydratase-aldolase from Pseudomonas putida (HBPA Pputida ) and (ii) subsequent 2-oxogroup reduction of the aldol adduct by ketopantoate reductase from E. coli (KPR Ecoli ) and a Δ1-piperidine-2-carboxylate/Δ1-pyrroline-2-carboxylate reductase from Pseudomonas syringae pv. tomato DSM 50315 (DpkA Psyrin ) with uncovered promiscuous ketoreductase activity. A total of 29 structurally diverse compounds were prepared: both enantiomers of 2-hydroxy-4-butyrolactone (>99% ee), 21 2-hydroxy-3-substituted-4-butyrolactones with the (2R,3S), (2S,3S), (2R,3R), or (2S,3R) configuration (from 60:40 to 98:2 dr), and 6 2-hydroxy-4-substituted-4-butyrolactones with the (2S,4R) configuration (from 87:13 to 98:2 dr). Conversions of aldol adducts varied from 32 to 98%, while quantitative conversions were achieved by both ketoreductases, with global isolated yields between 20 and 45% for most of the examples. One-pot one-step cascade reactions were successfully conducted achieving isolated yields from 30 to 57%.

| S-EPMC10127515 | biostudies-literature

Practical asymmetric synthesis of ?-hydroxy ?-amino acids via complimentary aldol reactions.

Project description:Orthogonally protected chiral ?-hydroxy-?-amino acids can be accessed in >100 g quantities from readily available starting materials and reagents in 3-4 steps. These chiral synthons contain two adjacent stereocenters along with suitably protected functional groups (O-TBS, N-Boc) for downstream reactivity. Implementation of two existing aldol technologies allows rapid access to all possible stereoisomers of 1. The guiding principles during reaction optimization were reaction scalability and operational efficiency. Conversion of the amino acids to a variety of chiral building blocks in 1-2 steps demonstrates their synthetic utility.

| S-EPMC3150486 | biostudies-literature

Tandem Aldol Condensation - Platinacycle-Catalyzed Addition Reactions of Aldehydes, Methyl Ketones and Arylboronic Acids.

Project description:Tandem aldol condensation of aldehydes with methyl ketones followed by anionic four-electron donor-based (Type I) platinacycle-catalyzed addition reactions of arylboronic acids to form ?-arylated ketones is described. Good to excellent yields of ?-arylated ketones were obtained for the tandem reactions of aromatic/aliphatic aldehydes, methyl ketones and arylboronic acids, and moderate yields were observed for the tandem reaction with ?, ?-unsaturated aldehydes as the aldehyde source.

| S-EPMC3547403 | biostudies-other

Prebiotic access to enantioenriched amino acids via peptide-mediated transamination reactions.

Project description:The kinetic resolution of racemic amino acids mediated by dipeptides and pyridoxal provides a prebiotically plausible route to enantioenriched proteinogenic amino acids. The enzymatic transamination cycles that are key to modern biochemical formation of enantiopure amino acids may have evolved from this half of the reversible reaction couple. Kinetic resolution of racemic precursors emerges as a general route to enantioenrichment under prebiotic conditions.

| S-EPMC10873602 | biostudies-literature

Enantioselective direct aldol reactions catalyzed by L-prolinamide derivatives.

Project description:l-Prolinamides 2, prepared from l-proline and simple aliphatic and aromatic amines, have been found to be active catalysts for the direct aldol reaction of 4-nitrobenzaldehyde with neat acetone at room temperature. They give moderate enantioselectivities of up to 46% enantiomeric excess (ee). The enantioselectivity increases as the amide N-H becomes a better hydrogen bond donor. l-Prolinamides 3, derived from the reaction of l-proline with alpha,beta-hydroxyamines such that there is a terminal hydroxyl group, show more efficient catalysis and higher enantioselectivities. In particular, catalyst 3h, prepared from l-proline and (1S,2S)-diphenyl-2-aminoethanol, exhibits high enantioselectivities of up to 93% ee for aromatic aldehydes and up to >99% ee for aliphatic aldehydes under -25 degrees C. Model reactions of benzaldehyde with three enamines derived from the condensation of prolinamides with acetone have been studied by quantum mechanics calculations. The calculations reveal that the amide N-H and the terminal hydroxyl groups form hydrogen bonds with the benzaldehyde substrate. These hydrogen bonds reduce the activation energy and cause high enantioselectivity. Our results suggest a new strategy in the design of new organic catalysts for direct asymmetric aldol reactions and related transformations.

| S-EPMC395980 | biostudies-literature

Aldol Reactions of Conformationally Stable Axially Chiral Thiohydantoin Derivatives.

Project description:Two novel axially chiral ortho-trifluoromethylphenyl thiohydantoin derivatives have been prepared atroposelectively from the reaction of R and S alanine methyl ester HCl salts with ortho-trifluoromethylphenyl isothiocyanate in the presence of triethyl amine. It was found that after purification of the crude product by simple recrystallization, the R amino acid esters yielded thiohydantoins having solely M axial chirality whereas the S ones returned the P isomers only. This result prompted us to perform sterically controlled aldol reactions on M and P thiohydantoin atropisomers. It was found that during the aldol reaction of 3-o-trifluoromethyl-5-methylthiohydantoins, the o-trifluoromethyl group of the M isomers efficiently shielded the Si face of the intermediate and in this way, enabled the selective formation of only the R configured aldol products at C5 of the heterocyclic ring. The P thiohydantoins, on the other hand, yielded only the S C5 configured aldol products as a result of the Re face shielding of the ortho-trifluoromethyl group of intermediate enolates. A noteworthy face selectivity of the benzaldehyde molecule was not observed (anti/syn only 3/2) during the aldolization of trifluoromethylphenyl derivatives of thiohydantoins. Aldol reactions were also done using the previously synthesized axially chiral thiohydantoins with ortho-Cl, Br, and I phenyl substituents which had predominantly P conformations (P/M ratios > 95%), and the stereochemical outcomes were compared with those of the ortho-trifluoromethyl substituted ones. 80-90% face selectivity of the benzaldehyde molecule was observed for the axially chiral o-halophenyl substituted thiohydantoins. The syntheses done with axially chiral 3-ortho-trifluoromethylphenyl- and 3-ortho-iodophenyl-5-methyl thiohydantoins enabled stereoselective formation of quaternized chiral carbon centers at C5 of the thiohydantoin ring.

| S-EPMC8552363 | biostudies-literature

Solid-Phase Synthesis of ?-Hydroxy Ketones Via DNA-Compatible Organocatalytic Aldol Reactions.

Project description:One-bead one-compound (OBOC) libraries constructed by solid-phase split-and-pool synthesis are a valuable source of protein ligands. Most OBOC libraries are composed of oligoamides, particularly peptides, peptoids, and peptoid-inspired molecules. Further diversification of the chemical space covered by OBOC libraries is desirable. Toward this end, we report here that the proline-catalyzed asymmetric aldol reaction, developed by List and Barbas for solution-phase synthesis, also works well for coupling immobilized aldehydes and soluble ketones. These reaction conditions do not compromise the amplification of DNA by the polymerase chain reaction. Thus, this chemistry should be useful for the construction of novel DNA-encoded OBOC libraries by solid-phase synthesis.

| S-EPMC6826340 | biostudies-literature

Three-component reductive conjugate addition/aldol tandem reaction enabled by nickel/photoredox dual catalysis.

Project description:A three-component reductive cross-coupling of aryl halides, aldehydes, and alkenes by nickel/photoredox dual catalysis is disclosed. The key to success for this tandem transformation is to identify α-silylamine as a unique organic reductant, which releases silylium ions instead of protons to prevent unwanted protonation processes, and meanwhile serves as Lewis acid to activate aldehydes in situ. This dual catalytic protocol completes a traditional conjugate addition/aldol sequence that eliminates the requirement of organometallic reagents and metal-based reductants, thus providing a mild synthetic route to highly valuable β-hydroxyl carbonyl compounds with contiguous 1,2-stereocenters.

| S-EPMC9906790 | biostudies-literature

Desymmetrization of enone-diones via rhodium-catalyzed diastereo- and enantioselective tandem conjugate addition-aldol cyclization.

Project description:Catalytic tandem conjugate addition-enolate trapping represents an effective strategy for the design of catalytic transformations that enable formation of multiple C-C bonds. Recently, using enantioselective rhodium-catalyzed conjugate addition methodology, we developed a catalytic tandem conjugate addition-aldol cyclization of keto-enones. Here, we report related desymmetrizations and parallel kinetic resolutions involving the use of diones as terminal electrophiles. The Rh-enolate generated on enone carbometallation effectively discriminates among four diastereotopic pi-faces of the appendant dione, ultimately providing products that embody four contiguous stereocenters, including two adjacent quaternary centers, with quantitative diastereoselection and high levels of enantiomeric excess. This methodology allows concise entry to optically enriched seco-B ring steroids possessing a 14-hydroxy cis-fused C-D ring junction, as found in naturally occurring cardiotonic steroids derived from digitalis.

| S-EPMC397397 | biostudies-literature

Novel Cinchona alkaloid derived ammonium salts as catalysts for the asymmetric synthesis of beta-hydroxy alpha-amino acids via aldol reactions.

Project description:Using the cinchonidine-derived phase-transfer catalyst de veloped by Park and Jew as a lead structure, we have prepared novel chiral ammonium salts and investigated their efficacy for the preparation of beta-hydroxy alpha-amino acids via asymmetric aldol reactions. The modifications were performed at C3 of the cinchonidine nucleus and include dimers as well as catalysts possessing electron-deficient alkyne and alkene moieties. Some of the new catalysts yielded improvements relative to the Park-Jew catalyst in the aldol reaction.

| S-EPMC1855095 | biostudies-other

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data