Microbial asymmetric reduction of α-hydroxyketones in the anti-Prelog selectivity

Yamadazyma farinosa IFO 10896 was found to reduce α-hydroxyketones bearing a phenyl ring to give optically active diols with anti-Prelog selectivity. The distance between the carbonyl group and the phenyl ring was shown to have an interesting effect on the reactivity and selectivity of the enzyme system.     

ATP-Independent and Cell-Free Biosynthesis of β-Hydroxy Acids Using Vinyl Esters as Smart Substrates

In vitro biosynthetic pathways that condense and reduce molecules through coenzyme A (CoASH) activation demand energy and redox power in the form of ATP and NAD(P)H, respectively. These coenzymes must be orthogonally recycled by ancillary reactions that consume chemicals, electricity, or light, impacting the atom economy and/or the energy consumption of the biosystem. In this work, we have exploited vinyl esters as dual acyl and electron donor substrates to synthesize β-hydroxy acids through a non-decarboxylating Claisen condensation, reduction and hydrolysis stepwise cascade, including a NADH recycling step, catalyzed by a total of 4 enzymes. Herein, the chemical energy to activate the acyl group with CoASH and the redox power for the reduction are embedded into the vinyl esters. Upon optimization, this self-sustaining cascade reached a titer of (S)-3-hydroxy butyrate of 24 mM without requiring ATP and simultaneously recycling CoASH and NADH. This work illustrates the potential of in vitro biocatalysis to transform simple molecules into multi-functional ones.     

Microbial deracemization of α-substituted carboxylic acids: control of the reaction path

A novel approach to preparing optically active α-substituted carboxylic acids using the whole cells of Nocardia diaphanozonaria JCM 3208 is described. When 2-phenylthiopropanoic acid and 2-methyl-3-phenylpropanoic acid were subjected to the reaction under aerobic conditions, the oxidation reaction proceeded preferentially rather than deracemization of these substrates. Herein, we report the design of reaction conditions to increase the deracemization activity in preference to oxidation reactions. In addition, we have successfully detected a metabolic intermediate in the reaction mixture of 2-methyl-3-phenylpropanoic acid, which indicates that the deracemization is a competitive reaction against the β-oxidation pathway of fatty acid metabolism.     

Effects of Phosphorus Substituents on Reactions of α-Alkoxyphosphonium Salts with Nucleophiles

The effects of phosphorus substituents on the reactivity of α-alkoxyphosphonium salts with nucleophiles has been explored. Reactions of α-alkoxyphosphonium salts, prepared from various acetals and tris(o-tolyl)phosphine, with a variety of nucleophiles proceeded efficiently. These processes represent the first examples of high-yielding nucleophilic substitution reactions of α-alkoxyphosphonium salts. The reactivity of these salts was determined by a balance between steric and electronic factors, respectively, represented by cone angles θ and CO stretching frequencies ν (steric and electronic parameters, respectively). In addition, a novel reaction of α-alkoxyphosphonium salts derived from Ph₃P with Grignard reagents was observed to take place in the presence of O₂ to afford alcohols in good yields. A radical mechanism is proposed for this process that has gained support from isotope-labeling and radical-inhibition experiments.     

Effective α-Tosyloxylation of Ketones Using 1,1,1-Trifluoro-2-iodoethane as Catalyst

With 1,1,1-trifluoro-2-iodoethane as catalyst, a novel and efficient procedure has been developed for preparation of α-tosyloxyketones from ketones. In this protocol, 1,1,1-trifluoro-2-iodoethane is first oxidized by m-chloroperbenzoic acid to a hypervalent iodine intermediate. The in situ–generated active iodine species then reacts with ketones to afford the corresponding α-tosyloxyketones in good yields.     

α-Amidoaldehydes as Substrates in Rhodium-Catalyzed Intermolecular Alkyne Hydroacylation: The Synthesis of α-Amidoketones

We show that readily available α-amidoaldehydes are effective substrates for intermolecular Rh-catalyzed alkyne hydroacylation reactions. The catalyst [Rh(dppe)(C₆H₅F)][BAr^F₄] provides good reactivity, and allows a broad range of aldehydes and alkynes to be used as substrates, delivering α-amidoketone products. High yields and high levels of regioselectivity are achieved. The use of α-amidoaldehydes as substrates establishes that 1,4-dicarbonyl motifs can be used as controlling groups in Rh-catalyzed hydroacylation reactions.     

Total Synthesis of Resorcylic Acid Lactone (−)-Neocosmosin A Using Palladium-Catalyzed α-Arylation of Enones as the Key Step

The total synthesis of the 14-membered resorcylic acid lactone neocosmosin A is described. The key step in the synthesis is the palladium-catalyzed α-arylation of TES-enol ethers of enones. The employment of the α-arylation approach to this class of resorcylic acid lactones is a new approach, which has the scope of being generalized into a unified approach for the synthesis of this class of natural products.     

Effects of Phosphorus Substituents on Reactions of α-Alkoxyphosphonium Salts with Nucleophiles

The effects of phosphorus substituents on the reactivity of α-alkoxyphosphonium salts with nucleophiles has been explored. Reactions of α-alkoxyphosphonium salts, prepared from various acetals and tris(o-tolyl)phosphine, with a variety of nucleophiles proceeded efficiently. These processes represent the first examples of high-yielding nucleophilic substitution reactions of α-alkoxyphosphonium salts. The reactivity of these salts was determined by a balance between steric and electronic factors, respectively, represented by cone angles θ and CO stretching frequencies ν (steric and electronic parameters, respectively). In addition, a novel reaction of α-alkoxyphosphonium salts derived from Ph(3) P with Grignard reagents was observed to take place in the presence of O(2) to afford alcohols in good yields. A radical mechanism is proposed for this process that has gained support from isotope-labeling and radical-inhibition experiments.     

Enzymatic Synthesis of Noncanonical α-Amino Acids Containing γ-Tertiary Alcohols

Noncanonical amino acids (ncAAs) containing tertiary alcohols are valuable as precursors of natural products and active pharmaceutical ingredients. However, the assembly of such ncAA scaffolds from simple material by C−C bond formation remains a challenging task due to the presence of multiple stereocenters and large steric hindrance. In this study, we present a novel solution to this problem through highly selective enzymatic decarboxylative aldol addition. This method allows for the streamlined assembly of multifunctionalized ncAAs with γ-tertiary alcohols from readily available materials, such as _L-aspartatic acid and isatins, vicinal diones and keto esters. The modularity of electrophiles furnished four classes of ncAAs with decent efficiency as well as excellent site and stereocontrol. Computational modeling was employed to gain detailed insight into the catalytic mechanism and to provide a rationale for the observed selectivities. The method offers a single-step approach to producing multifunctionalized ncAAs, which can be directly utilized in peptide synthesis and bioactivity assessment.     

Mechanical Properties of Silicone Rubber Using Carbosilane Dendrimers as the Cross-linker

Peroxide-cured high-temperature vulcanized （HTV） silicone rubber was prepared by using allyl-capped carbosilane dendrimers, in which the core molecule is Si（CHaCH=CH2）4, as the cross-linker. It showed that this kind of allyl-capped carbosilane dendrimer improved the mechanical properties of silicone rubber.     

Facile Synthesis of α-Haloketones by Aerobic Oxidation of Olefins Using KX as Nonhazardous Halogen Source

Summary of main observation and conclusion An operationally simple and safe synthesis of a-haloketones using KBr and KCI as nonhazardous halogen sources is reported.It involves an iron-catalysed reaction of alkenes with KBr/KCl using O2 as terminal oxidant under the irradiation of visible-light.This strategy avoids the risks associated with handling halo-contained electrophiles(Cl2,Br2/NCS,NBS).The process is tolerant to several functional groups,and extended to a range of substituted styrenes in up to 89%yield.A radical reaction pathway is proposed based on control experiments and spectroscopy studies.     

A Sensitive Method for the Determination of Methadone in Biological Samples Using Nano-Structured α-Carboxy Polypyrrol as a Sorbent of SPME

Nano-structured α-carboxy polypyrrol (PPy- α-COOH) was used as a coating of solid-phase microextraction (SPME) fiber to increase the extraction efficiency of headspace solid phase microextraction (HS-SPME) of methadone (MDN) in biological samples. The carboxy-endcapped polypyrrole film was prepared via electrochemical deposition on a platinum wire. A nano-fibrous structure of PPy-α-COOH with a diameter of 120 nm was obtained. The porous surface structure of the film, revealed by scanning electron microscopy, provided high surface areas and allowed for high extraction efficiency of methadone. Then the analysis of the extracts was carried out by a gas chromatography-flame ionization detector. In order to achieve maximum extraction efficiency, different parameters affecting the extraction conditions were optimized. Under the optimized conditions, the limit of detections and the limit of quantifications of the method in the range of 0.02–0.035 and 0.06–0.10 μg L⁻¹ were obtained for different matrices. The relative recoveries in different samples were in the range of 95–97%. Finally, the feasibility of the proposed method was successfully confirmed by extraction and determination of MDN in human urine and plasma samples in the range of microgram per liter, and suitable results were obtained (RSDs <5.3%).

     

Studies on the Microbial Synthesis and Characterization of Polyhydroxyalkanoates Containing 4-Hydroxyvalerate Using γ-Valerolactone

In this study, the ability of Cupriavidus sp. USMAA2-4 to synthesize polyhydroxyalkanoates (PHA) containing 4-hydroxyvalerate monomer (4HV) was studied through one-stage cultivation using γ-valerolactone as the carbon precursor. The presence of 4HV monomer unit in the polymer was detected through gas chromatography analysis, proving the capability of this wild strain bacterium to produce poly(3-hydrxybutyrate-co-3-hydroxyvalerate-co-4-hydroxyvalerate) [P(3HB-co-3HV-co-4HV)] terpolymer. Existence of a 4HV monomer unit in the PHA produced was further confirmed through ¹³C and ¹H NMR analysis. P(3HB-co-88 % 3HV-co-1 % 4HV) terpolymer with the highest PHA content of 63 wt% was obtained through combination of 0.14 wt% C of γ-valerolactone with 0.42 wt% C of oleic acid. Various compositions of P(3HB-co-3HV-co-4HV) terpolymer with 3HV and 4HV compositions ranging from 11 to 94 mol% and from 1 to 4 mol%, respectively, were acquired by manipulating γ-valerolactone and oleic acid concentrations. The molecular weight and the thermal and mechanical properties of four different compositions of terpolymers—P(3HB-co-91 % 3HV-co-1 % 4HV), P(3HB-co-55 % 3HV-co-2 % 4HV), P(3HB-co-27 % 3HV-co-2 % 4HV), and P(3HB-co-9 % 3HV-co-1 % 4HV)—were characterized. Among these terpolymers, P(3HB-co-27 % 3HV-co-2 % 4HV) terpolymer with a molecular weight of 5.7 (10⁵ Da) exhibited the highest elongation to break (264 %). The monomer unit compositional distributions of these terpolymers were investigated through acetone–water fractionation analysis. The results suggested that these produced terpolymers had broad 3HV compositional distribution and narrow 4HV compositional distribution.     

Asymmetric aminocarbonylation of iodoalkenes in the presence of α-phenylethylamine as an N-nucleophile

Iodoalkenes, such as 2-iodo-bornene, 17-iodoandrost-16-ene, 3-methoxy-17-iodoestra-1,3,5(10),16-ene, 3β-hydroxy-20-iodopregna-5,20-diene and 3β-hydroxy-12-iodo-5α,25R-spirost-11-ene were aminocarbonylated with enantiomerically pure and racemic α-phenylethylamine as the N-nucleophile in the presence of palladium(0) catalysts. Monodentate and bidentate (chiral and achiral) phosphines were used as ligands in the catalytic system. All diastereoisomers of the corresponding carboxamides were characterised as pure stereoisomers using both α-phenylethylamine and iodoalkene in enantiomerically pure form. The diastereoisomers were obtained in moderate to high yields in a chemoselective reaction, i.e., carboxamides due to single carbon monoxide insertion were formed exclusively, with no double CO insertion leading to 2-ketocarboxamides. Diastereoselectivities of the aminocarbonylation were investigated using the N-nucleophile in racemic form by the systematic variation of the catalyst.     

Aminopyridines as amino components in the catalytic synthesis of α-aminophosphonates

6h-Aminophosphonates containing alicyclic, aromatic, and heterocyclic fragments were obtained in high yields by the Kabachnick—Fields reaction of the corresponding carbonyl compounds with 2-, 3- and 4-aminopyridines and diethyl phosphite using tetra- tert-butyl- phthalocyanine aluminum chloride as the catalyst. 2-, 3-, 4-Aminopyridines were found to vary in their reactivity with ketones and diethyl phosphite in the catalytic three-component one-pot process.     

Aza-Michael Addition of Amines to α,β-Unsaturated Compounds Using Molecular Iodine as Catalyst

Aza-Michael adducts are obtained in very good yields by the conjugate addition of aliphatic amines to α,β-unsaturated compounds using molecular iodine as catalyst in dichloromethane at room temperature. Aromatic amines were found to be reactive under reflux in toluene.     

Diphenylparabanic acid as a synthon for the synthesis of α-diketones and α-ketocarboxylic acids

Diphenylparabanic acid was found to react with >2 equiv of organolithiums at -78 °C to effectively give the corresponding symmetrical α-diketones. However, upon treatment with 1 equiv of organolithium, the parabanic acid gave mainly 5-substituted 5-hydroxyimidazolidine-2,4-diones. On the other hand, Grignard reagents were less reactive toward the parabanic acid at low temperature, and selectively gave the corresponding 5-hydroxyimidazolidine-2,4-diones even if more than 1 equiv of the reagents was used. A tandem process in which the parabanic acid was first reacted with a Grignard reagent and then reacted in one-pot with an organolithium effectively gave the unsymmetrical α-diketone. 5-Substituted 5-hydroxyimidazolidine-2,4-diones were useful as versatile precursors for preparing α-ketocarboxylic acids as well as unsymmetrical α-diketones.     

Scope and Limitations in the Use of α-Silyl and α-Stannyl Sulfones as Latent α-Sulfonyl Anions

Three methods for the regeneration of α-sulfonyl anions from α-silyl sulfones and α-stannyl sulfones are investigated. These methods include: (1) treatment of α-silyl sulfones with electrophiles (aldehydes and acid halides) in the presence of fluoride ion; (2) reaction of α-silyl sulfones with n-butyllithium which produces an α-silyl anion via a migration of the -SiMe₃ group from the α-position to the ortho-position of the phenyl sulfones; and (3) direct transmetalation of α-stannyl sulfone by treatment with n-butyllithium. The addition of cerium [III] chloride is shown to substantially decrease enolization problems associated with addition of α-sulfonyl anions to carbonyl compounds bearing enolizable protons.     

Formation of Heterocyclic α-Oxo Thioketones Using N-Chlorosulfenylsuccinimide

N-Chlorosulfenylsuccinimide is a suitable reagent for the generation of heterocyclic -oxo thioketones. The latter readily undergo [4 + 2] cycloaddition with 1,3-dienes to give heterocyclic compounds containing spirocyclic thiine substituents.     

Using Diaminomethanal as an Entrainer for the Separation of Isopropanol + Water Mixture

Journal of Solution Chemistry - Diaminomethanal (an organic compound), was examined as entrainer for dehydration of isopropanol?water system by extractive distillation. Isobaric...