Β-carbonyl Group Research Articles

Repeatedly Recyclable 3D Printing Catalyst-free Dynamic Thermosetting Photopolymers.

Photo-curing 3D printing technology has promoted the advanced manufacturing in various fields, but has exacerbated the environmental crisis by the demand for the chemically cross-linked thermosetting photopolymers. Here, we report a generic strategy to develop catalyst-free dynamic thermosetting photopolymers, based on photopolymerization and transesterification, that can enable users to realize repeatable 3D printing, providing a practical solution to the environmental challenges. We demonstrate that the β-carbonyl group adjacent to the ester group greatly accelerates the rate of transesterification. The generated resins from the immobilization of the catalyst-free reversible bonds into the photopolymers leads to a dynamic covalently crosslinked network structure upon UV based 3D printing, which exhibit controllable mechanical properties with elastomeric behaviors to thermadapt shape memory polymers. Furthermore, the resulting network can be reverted into an acrylate-functioned photopolymer that is suitable for 3D printing again, presenting an on-demand, repeatedly recyclable thermosetting photopolymer platform for sustainable 3D printing. This article is protected by copyright. All rights reserved.

Asymmetric Alkoxy- and Hydroxy-Carbonylations of Functionalized Alkenes Assisted by β-Carbonyl Groups.

As a fundamental type of carbonylation reaction, the alkoxy- and hydroxy-carbonylation of unsaturated hydrocarbons constitutes one of the most important industrial applications of homogeneous catalysis. However, owing to the difficulties in controlling multi-selectivities for asymmetric hydrocarbonylation of alkenes, this reaction is typically limited to vinylarenes and analogues. In this work, a highly efficient asymmetric alkoxy- and hydroxy-carbonylation of β-carbonyl functionalized alkenes was developed, providing practical and easy access to various densely functionalized chiral molecules with high optical purity from broadly available alkenes, CO, and nucleophiles (>90 examples, 84-99 % ee). This protocol features mild reaction conditions and a broad substrate scope, and the products can be readily transformed into a diverse array of chiral heterocycles. Control experiments revealed the key role of the β-carbonyl group in determining the enantioselectivity and promoting the activity, which facilitates chiral induction by coordination to the transition metal as rationalized by DFT calculations. The strategy of utilizing an innate functional group as the directing group on the alkene substrate might find further applications in catalytic asymmetric hydrocarbonylation reactions.

Asymmetric Total Synthesis of (-)-Guignardones A and B.

The asymmetric total synthesis of (-)-guignardones A (2) and B (1) has been accomplished. The highly oxidized 6-oxabicyclo[3.2.1]octane core was constructed from d-quinic acid via substitution/desulfurization reaction with thiophenol to forge the bridged ring scaffold, and a Pummerer rearrangement and 1,4-addition/elimination sequence was employed to install the β-carbonyl group at the congested C-1 position. A late-stage Knoevenagel condensation-6π-electrocyclization and directed hydrogenation formed (-)-guignardone B (1), which was subjected to dehydration to furnish (-)-guignardone A (2).

Construction of a series of intermediates in the β-oxidation pathway from THA to EPA via DHA in free acid form

β-Oxidation of most fatty acids occurs in the mitochondria. However, β-oxidation for ω-3 polyunsaturated fatty acids (PUFAs) is distinct from abundant fatty acids and occurs in the peroxisomes. Since little is known about peroxisomal β-oxidation, here we report the synthesis of proposed intermediates of ω-3 PUFA β-oxidation steps in free fatty acid form having a conjugated double bond, a β-hydroxyl group, a β-olefin and a β-carbonyl group. These fatty acids can serve as authentic samples for biological experiments.

Ethylenedioxy homologs of N-methyl-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA) and its corresponding cathinone analog methylenedioxymethcathinone: Interactions with transporters for serotonin, dopamine, and norepinephrine

N-Methyl-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA; ‘Ecstasy’; 1) and its β-keto analog methylone (MDMC; 2) are popular drugs of abuse. Little is known about their ring-expanded ethylenedioxy homologs. Here, we prepared N-methyl-(3,4-ethylenedioxyphenyl)-2-aminopropane (EDMA; 3), both of its optical isomers, and β-keto EDMA (i.e., EDMC; 4) to examine their effects at transporters for serotonin (SERT), dopamine (DAT), and norepinephrine (NET). In general, ring-expansion of the methylenedioxy group led to a several-fold reduction in potency at all three transporters. With respect to EDMA (3), S(+)3 was 6-fold, 50-fold, and 8-fold more potent than its R(−) enantiomer at SERT, DAT, and NET, respectively. Overall, in the absence of a β-carbonyl group, the ethylenedioxy (i.e., 1,4-dioxane) substituent seems better accommodated at SERT than at DAT and NET.

α,β → β,γ double bond migration in corallopyronin A biosynthesis

In polyketide biosynthesis the reduction of β-carbonyl groups to an alkene usually results in a α,β double bond. However, in a few antibiotics the rare case of such a carbon–carbon double bond in β,γ position is observed. The in vivo active antibiotic corallopyronin A represents such a molecule, whereby a α,β → β,γ double bond migration takes place during the assembly of the molecule. Here we report the in vitro analysis of the enzyme domain responsible for this double bond isomerization. This “shift domain” was heterologously expressed and assayed with its acyl carrier protein bound substrate. To facilitate this analysis the biosynthetic corallopyronin A intermediate was chemically synthesized as a SNAC-derivative. Enzyme activity was analyzed by NMR and high-resolution MS measurements, the latter enabled by performing the assay in deuterated buffer. Mutated enzyme variants gave first experimental evidence for the essential amino acids involved in double bond migration. These results further support the proposed corallopyronin A biosynthesis.

Synthesis and Anti-Cancer Activity of C-Ring-Functionalized Prodigiosin Analogues

Prodigiosin is the parent member of the 4-methoxypyrrolyldipyrromethene family of natural products and is known for its anti-cancer activity. A new series of analogues was synthesized, incorporating pendent functional esters and beta-carbonyl substituents on the C-ring. The beta-carbonyl group allowed for the facile isolation of the prodigiosenes, and the pendent esters allow for further derivatization. The novel prodigiosenes generally retain the anti-cancer activity of prodigiosin in 60 human cell lines derived from nine cancer cell types, with neither the conjugated beta-carbonyl group, as either ketone or ester, nor the pendent ester significantly reducing the anti-cancer activity of the core skeleton.

Nonnucleoside HIV-1 reverse transcriptase inhibitors; part 3. Synthesis and antiviral activity of 5-alkyl-2-[(aryl and alkyloxyl-carbonylmethyl)thio]-6-(1-naphthylmethyl) pyrimidin-4(3 H)-ones

A series of 6-naphthylmethyl substituted S-alkylated dihydroalkoxybenzyloxopyrimidine ( S-DABO) analogues with a β-carbonyl group on the C-2 side chain were synthesized. All of the new compounds were evaluated for their anti-HIV activities in MT-4 cells. The most active compound, 5-isopropyl-2-[(4 ′-methoxyphenylcarbonyl-methyl)thio]-6-(1-naphthylmethyl)pyrimidin- 4(3 H)-one showed activity against HIV-1 and against the double mutated strain of HIV(Y181C and K103N) in the micromolar range. Furthermore, some of the compounds are active against both HIV-1 and HIV-2 in cell culture. In view of the fact that the loss of antiviral activity of these compounds when tested against S0561945 was much less pronounced than the loss of activity of typical NNRTIs, it is concluded that some of the compounds might interfere with another target or act on reverse transcriptase in a different way than the typical NNRTIs.

5-Alkyl-2-[(aryl and alkyloxylcarbonylmethyl)thio]-6-(1-naphthylmethyl) pyrimidin-4(3 H)-ones as an unique HIV reverse transcriptase inhibitors of S-DABO series

The introduction of a β-carbonyl group to the C-2 side chain of S-DABO led to the finding of a series of novel potent anti-HIV agent. Some derivatives proved to be highly effective in inhibiting HIV-1 replication at nanomolar concentrations. Furthermore, the novel S-DABOs differ from the classical NNRTIs in that some compounds are active against both HIV-1 and HIV-2. They might interfere with another target or at least act on RT in a different way as compared to typical NNRTIs.

New insights into the reduction of β,δ-diketo-sulfoxides

New developments in the reduction of β,δ-diketo-sulfoxides, a reaction that affords important key intermediates for total synthesis, are described. We showed without ambiguity using NMR experiments, that the β-carbonyl group is totally enolised. This result is inconsistent with the previous hypothesis, which supposed the other tautomer (enolisation at the δ-position) as the major one. We propose a rationale to explain the side reactions occurring during the reduction of unprotected β,δ-diketo-sulfoxides and showed that judicious protection of the δ-carbonyl group gave all diastereoisomers of β-hydroxy-δ-ketosulfoxides.

4′-{[Benzoyl(4-nitrophenylhydrazono)methyl]sulfonyl}acetanilide

The conformation of the title compound, C22H18N4O6S, is stabilized by a strong resonance-assisted intramolecular hydrogen bond linking the hydrazone moiety and the sulfonyl group. The resulting six-membered ring is practically planar. Short intramolecular contacts link oppositely charged atoms of the sulfonyl and β-carbonyl groups. The crystal packing is influenced by intermolecular hydrogen bonds involving the β-carbonyl O atoms and the N—H bonds of the terminal acet­amide moieties.

UV photoelectron and ab initio study of intramolecular interactions in α-diethoxyphosphoryl carbonyl derivatives

Information on the geometric and electronic structures of α-diethoxyphosphoryl carbonyl derivatives, (RO) 2P(O)CH 2C(O)X, ( 1– 5, X=CH 3 1, CH 3CH 2O 2, CH 3CH 2S 3, C 6H 5 4, (CH 3CH 2) 2N 5), is obtained by UV photoelectron spectroscopy and ab initio calculations. At the HF level, the CH 2–P bond is gauche to the carbonyl group except in 5. However, at the DFT and MP2 levels, the gauche conformation prevails for all the derivatives, in agreement with the spectroscopic data. This conformation is dictated by the interplay of the electronic interactions between the XC(O) and (RO) 2P(O) groups with two short contacts between pairs of oppositely charged atoms. The negatively charged carbonyl oxygen and one of the oxygen atoms bonded to phosphorus lie at distances shorter than (or close to) the sum of the corresponding van der Waals radii from the positively charged phosphorus and carbonyl carbon atom, respectively. The presence of through-space interactions in the ground and ionised states is confirmed by eigenvector analysis and by the shifts in the MO energies with respect to those of reference compounds. In the ground state the non-bonded interactions are weaker than the corresponding interactions in β-carbonyl sulphones, RSO 2CH 2C(O)X, because of the less suitable geometry of the PO 3 group, with respect to the SO 2R group, for interaction with the β-carbonyl group. In the ionised state, however, the negative charge on the oxygens of the phosphoryl group has a greater capacity to relax toward the ionised XC(O) group thus reducing the ionisation energy values.

The fungicidal activity of β-keto sulfones. Molecular conformation of α-phenylhydrazono-β-ketosulfones as determined by an X-ray analysis

The solid-state conformations of eight (1-phenylhydrazono-2-oxo-2-phenylethyl)-phenyl sulfones and four (1-phenyl-1-phenylhydrazono-2-oxo-2 phenylethyl)-phenyl sulfones have been analyzed. All compounds adopt conformations which maximize the gauche or cis type of interaction between the sulfur-oxygen double bonds and large polar substituents situated in α positions with respect to the sulfonyl groups. The charge distribution strongly favours stereoelectronic effects. The conformation of (1-phenylhydrazono-2-oxo-2-phenylethyl)-phenyl sulfones is mostly stabilized by strong, intramolecular, resonance-assisted hydrogen bonds supplemented by charge transfer from β-carbonyl groups towards the sulfonyl groups. In the second group of sulfones, the donation of electron density from N(2) atoms of the hydrazone moiety to the sulfur atoms is the main stereoelectronic interaction.

Highly Potent Bisphosphonate Ligands for Phosphoglycerate Kinase and Protein Binding Studies

Several novel α,ω-bisphosphonate analogs (1) of 1,3-bisphospho-D-glyceric acid, 1,3-BPG (2) have been made and their binding to phosphoglycerate kinase, PGK (EC 2.7.2.3) evaluated. Non-scissile methanephosphonic acids replace the two phosphate monoesters of 1,3-BPG. Fluorine substitution in the α-methylene groups of the phosphonic acid analogs (1) markedly improves their binding to PGK as determined by NMR analysis. The best ligands bind some 50-100 times more strongly than does 3-phospho-D-glyceric acid and show a requirement for pK a3 to be below 6.0 while the presence of a β-carbonyl group (1, Y = CO) seems to be of secondary importance. One analog, 1,1,5,5-tetrafluoropentanebisphosphonic acid, has been linked to adenosine 5′-phosphate and 5′-diphosphate to generate bisubstrate analogs (3) whose affinity for PGK and an X-ray crystal structure of a binary complex with PGK will be discussed.

Highly Potent Bisphosphonate Ligands for Phosphoglycerate Kinase and Protein Binding Studies

Several novel α,ω-bisphosphonate analogs (1) of 1,3-bisphospho-D-glyceric acid, 1,3-BPG (2) have been made and their binding to phosphoglycerate kinase, PGK (EC 2.7.2.3) evaluated. Non-scissile methanephosphonic acids replace the two phosphate monoesters of 1,3-BPG. Fluorine substitution in the α-methylene groups of the phosphonic acid analogs (1) markedly improves their binding to PGK as determined by NMR analysis. The best ligands bind some 50-100 times more strongly than does 3-phospho-D-glyceric acid and show a requirement for pK a3 to be below 6.0 while the presence of a β-carbonyl group (1, Y = CO) seems to be of secondary importance. One analog, 1,1,5,5-tetrafluoropentanebisphosphonic acid, has been linked to adenosine 5′-phosphate and 5′-diphosphate to generate bisubstrate analogs (3) whose affinity for PGK and an X-ray crystal structure of a binary complex with PGK will be discussed.

Rate-determining carbonyl hydration in the intramolecular hydrolysis of phenacyl phosphonate esters: isotopic probes and activation parameters

4-Nitrophenyl 4-substituted-phenacyl methylphosphonate esters (CH 3 , H, CH 2 O, NO 2 , and Cl) decompose in aqueous buffers 1-4 orders of magnitude faster than analogs with alkoxy substituents not containing a β-carbonyl group. This is consistent with an intramolecular displacement of 4-nitrophenol by the anion of the carbonyl hydrate. 18 O incorporation into the hydrolysis product of the 4-CH 3 derivative from H 2 18 O in alkaline solution is 5 indicates a rapid protonic equilibrium between the carbonyl hydrate and the medium but slower equilibration of the carbonyl O with the medium than cyclization

Synthesis of tricarbonyliron(0) complexes of itaconic acid derivatives

The products derived from [Fe2(CO)9] and alkenes bearing β-carbonyl groups linked to the alkene via nitrogen, oxygen and carbon atoms are reported; in particular, derivatives of itaconic acid produce air-stable crystalline tricarbonyliron(O) complexes one of which [Feo(CO)3{MeO2CCH2C(CO2But)CH2}]21 was examined by X-ray crystal structure analysis.

Cobalt(II), nickel(II), copper(II) and zinc(II) complexes of conjugated 3-(benzylidene/salicylidene)-β-diketones (having no enolisable γ-carbon proton) and their reactions

The synthesis and structural characterization of new metal(II) chelates (M = CoII, NiII, CuII and ZnII) of neutral conjugated bidentate β-diketone ligands, having no enolisable γ-carbon proton, and their reactions are reported. The ligand systems chosen are Knoevenagal condensates of aromatic aldehydes with β-diketones, such as 3-(benzylidene/salicylidene) acetylacetone/benzoylacetone. The general composition of the chelates is [M(AA)B2C2] for 6-coordinate complexes and [M(AA)B2] for 4-coordinate complexes. (AA) is a neutral bidentate aldehyde-β-diketone condensate ligand; B is a mono-dentate anion and C is monodentate neutral ligand (H2O/Py). Bromination at α-methyl groups by NBS and PyHBr3, Schiff base condensation at β-carbonyl groups by amine bases and 1,2-addition reaction at the γ-carbon double bond are reported.

Intramolecular and intermolecular hydrogen bonds with participation of the enol proton of the 2-acetylcyclopentane-1,3-dione molecule

A study has been made of the IR spectra of 2-acetylcyclopentane-1,3-dione (ACPD) in various solvents. This is a compound with an exocyclic enol group bonded to one of the β-carbonyl groups by an intramolecular hydrogen bond (IAHB). The IAHB remains in the ACPD when it is dissolved in a nonpolar solvents such as CCl4 or cyclohexane, or when a weak proton acceptor such as CH3CN or dioxane is present; in polar basic-type solvents (pyridine, isoquinoline, triethylamine), the enol proton dissociates, forming an ion pair. In the presence of a strong proton acceptor such as hexametapol (HMP) or tetrabutylammonium bromide (TBAB), an equilibrium exists between the ACPD and its open form with an opened chelate ring in which the OH group is connected by an intermolecular hydrogen bond (IEHB) to the acceptor. According to13C NMR spectroscopic data, dissolution of ACPD in CD3COOD also gives the open form of ACPD, which is stabilized primarily by an IEHB between the COOD groups of the solvent and the C=O groups of the ACPD. By the method of competing equilibria in the IR spectroscopic version, the energies of the H-bonds involving the ACPD have been determined (values in kcal/ mole): ΔHIEHB with HMP=−11.7 ± 0.3; ΔHIEHB with TBAB=−10.9 ± 0.3; ΔHIAHB in ACPD=−6.6 ± 0.4.

ChemInform Abstract: Reduction of Unsaturated β‐Oxo Esters: Synthesis of Unsaturated β‐Hydroxy Esters and of Unsaturated 1,3‐Diols.

AbstractDie ungesättigten β‐Oxoester (I) werden mit NaBH4 selektiv zu den β‐Hydroxyderivaten (II) reduziert.