Search

A new family of chiral selectors was synthesized in a single synthetic step with yields up to 84% starting from isomannide and isosorbide. Mono- or disubstituted carbamate derivatives were obtained by reacting the isohexides with electron-donating arylisocyanate (3,5-dimethylphenyl- or 3,5-dimethoxyphenyl-) and electron-withdrawing arylisocyanate (3,5-bis(trifluoromethyl)phenyl-) groups to test opposite electronic effects on enantiodifferentiation. Deeper chiral pockets and derivatives with more acidic protons were obtained by derivatization with 1-naphthylisocyanate and

The experimental execution of chemical reactions is a context-dependent and time-consuming process, often solved using the experience collected over multiple decades of laboratory work or searching similar, already executed, experimental protocols. Although data-driven schemes, such as retrosynthetic models, are becoming established technologies in synthetic organic chemistry, the conversion of proposed synthetic routes to experimental procedures remains a burden on the shoulder of domain experts. In this work, we present data-driven models for predicting the entire sequence of synthesis steps starting from a textual representation of a chemical equation, for application in batch organic chemistry. We generated a data set of 693,517 chemical equations and associated action sequences by extracting and processing experimental procedure text from patents, using state-of-the-art natural language models. We used the attained data set to train three different models: a nearest-neighbor model based on recently-introduced reaction fingerprints, and two deep-learning sequence-to-sequence models based on the Transformer and BART architectures. An analysis by a trained chemist revealed that the predicted action sequences are adequate for execution without human intervention in more than 50% of the cases., In organic chemistry, synthetic routes for new molecules are often specified in terms of reacting molecules only. The current work reports an artificial intelligence model to predict the full sequence of experimental operations for an arbitrary chemical equation.

The synthesis, structure and properties of three hybrid polymers based on zinc arylphosphates are described in this study. Zinc bis(diphenylphosphate) (ZnDPhP) was obtained as needle-like crystals containing hexagonally packed, homochiral 1∞[Zn(DPhP)2/2] helical chains. The XRD and DSC studies revealed that upon heating, ZnDPhP undergoes a reversible thermal transition at ca. 160 °C with expansion mainly perpendicular to its c-axis. Zinc phenylphosphate hydrate (ZnMPhP-H) formed plate-like particles with an average thickness of less than 1 μm and much thinner nanolayers with a basal spacing of 15.5 A. ZnMPhP-H was easily and reversibly dehydrated to its anhydrous form, ZnMPhP-A, which exhibited a somewhat larger basal spacing of 16.5 A and the capacity for amine intercalation. The thermal decomposition of ZnDPhP or ZnMPhP-A began around 250 °C, resulting in the formation of solid mixtures of zinc phosphates and electron-conducting carbonaceous phases. The bulk electrical conductivities of the poly(vinylidene fluoride)-based composites containing the ZnDPhP pyrolyzates reached 0.1–0.2 S cm−1. Upon mixing with silicone oil, all the synthesized hybrid polymers formed fluids that exhibit significant negative electrorheological effects and have potential for application in electroresponsive smart materials. The application of an electric field during the crosslinking of such systems affected the viscoelastic properties of the resultant solid composites, while the cured systems showed rather small electrorheological effects.

This work investigates the potential application of various sterilization methods for microorganism inactivation on the thermoplastic starch blend surface. The influence of the e-beam and UV radiation, ethanol, isopropanol and microwave autoclave on structural and packaging properties were studied. All the applied methods were successful in the inactivation of yeast and molds, however only the e-beam radiation was able to remove the bacterial microflora. The FTIR analysis revealed no significant changes in the polymer structure, nevertheless, a deterioration of the mechanical properties of the blend was observed. The least invasive method was the UV radiation which did not affect the mechanical parameters and additionally improved the barrier properties of the tested material. Moreover, it was proved that during the e-beam radiation the chain scission and cross-linking occurred. The non-irradiated and irradiated samples were subjected to the enzymatic degradation studies performed in the presence of amylase. The results indicated that irradiation accelerated the decomposition of material, which was confirmed by the measurements of weight loss, and mass of glucose and starch released to the solution in the course of biodegradation, as well as the FTIR and thermal analysis. Electronic supplementary material The online version of this article (10.1007/s10924-020-01972-9) contains supplementary material, which is available to authorized users.

In the last few years, a very wide range of oligocarbonate diols, oligomers of carbonic acid esters terminated on both sides with hydroxyl groups, have appeared on the chemical market. They are mainly used for the production of flexible segments in precious grades of polyurethanes used in biomedical engineering. Poly(carbonate-urethane) due to high resistance to oxidizing and hydrolytic agents is also an attractive material for the production of adhesives and coatings with increased resistance to weather conditions. This paper presents the current state of knowledge on the methods of synthesis and main producers of oligomerols with carbonate groups, methods of poly(carbonate-urethane) synthesis and examples of its commercial applications.

Gamma-decalactone is an interesting flavuring compound with an intense oily-peachy aroma. It is commonly used in food and cosmetic industry. Biotechnological methods of its synthesis are based on the processes of fatty acid degradation, mainly ricinoleic acid, which is the main component of castor oil. The aim of this study was to compare the productivity of gamma-decalactone in batch cultures of two strains of Yarrowia lipolytica, wild strain W29 and its derived mutant MTLY40-2p, grown in flasks and a bioreactor. We analyzed the concentration of gamma-decalactone in the aqueous and oil phase, the optical density of the medium, the yield of yeast dry matter and the particle size distribution in the particular media. The modified strain had a higher aroma synthesis capacity. This strain grown in flasks produced thrice as much gamma-decalactone (5.5 ± 0.16 g/L) as compared to the wild-type strain (1.8 ± 0.03 g/L). During the 7-day biotransformation, the mutant strain did not have the ability to degrade gamma-decalactone, whereas in the biotransformation using the wild-type strain, reutilization was observed after the third day. Regardless of the type of culture, larger amounts of gamma-decalactone were accumulated in the lipid phase. Cultivation in a bioreactor resulted in a lower biomass yield and a lower concentration of lactone compared to flask culture, regardless of the strain used. The MTLY40-2p strain grew in mycelium form and tended to aggregate cells.

Organic compounds showing circularly polarized luminescence (CPL) are at the forefront of novel applications and technologies. Here we show the synthesis and chiroptical properties of pyrene and perylene derivatives of inexpensive chiral scaffolds: isomannide and isosorbide. Low-intensity ECD spectra were obtained, suggesting the absence of chromophore interaction in the ground state, except in the case of isomannide bis-perylenecarboxylate, whose ECD spectrum showed a positive exciton couplet. All isomannide derivatives, with the only exception of the one containing a pyrenecarboxylate and a perylenecarboxylate, exhibited excimer CPL spectra, whereas isosorbide derivatives did not show any CPL. Isomannide derivatives bearing two pyrenecarboxylate or two pyrenylacetate groups showed positive CPL emission with dissymmetry factors up to 10

We present an extension of our Molecular Transformer model combined with a hyper-graph exploration strategy for automatic retrosynthesis route planning without human intervention. The single-step retrosynthetic model sets a new state of the art for predicting reactants as well as reagents, solvents and catalysts for each retrosynthetic step. We introduce four metrics (coverage, class diversity, round-trip accuracy and Jensen–Shannon divergence) to evaluate the single-step retrosynthetic models, using the forward prediction and a reaction classification model always based on the transformer architecture. The hypergraph is constructed on the fly, and the nodes are filtered and further expanded based on a Bayesian-like probability. We critically assessed the end-to-end framework with several retrosynthesis examples from literature and academic exams. Overall, the frameworks have an excellent performance with few weaknesses related to the training data. The use of the introduced metrics opens up the possibility to optimize entire retrosynthetic frameworks by focusing on the performance of the single-step model only., We present an extension of our Molecular Transformer model combined with a hyper-graph exploration strategy for automatic retrosynthesis route planning without human intervention.

Both aryl and alkylzinc halides prepared by direct insertion of zinc into organic halides in the presence of LiCl underwent the conjugate addition reaction to nonenolizable unsaturated ketones in excellent yield, provided that DME was used instead of THF as the solvent. Diffusion NMR measurements highlighted that the species undergo considerable aggregation under the experimental conditions used in the synthetic procedure, but no substantial differences have been found between the two solvents. Density functional theory calculations, prompted by the experimental aggregation study, revealed an unexpected reaction mechanism, where the coordinating capabilities of DME stabilize a transition state involving two organozinc moieties, lowering the activation energy of the reaction with respect to that seen for THF, enough to explain the fast and quantitative reactions observed experimentally and the different behaviors of the two solvents., The reaction mechanism of a new conjugate addition reaction of organozinc halides to enones is disclosed by a combined experimental/computational study.

In the presented paper, two basic strategies that can be used in the processes of chemical recycling of polyester material were described. The first of them involves increasing the molar mass of recycled materials in the solid-state polycondensation (SSP) process and/or joining their chains with various types of substances easily reacting with the end groups of polyesters (so-called extending agents). The essence of the second strategy is the degradation of the material under the influence of various protogenic agents (such as water, alcohols, glycols and amines) to obtain low-molecular products or oligomers that can be used as raw materials in the synthesis of many classes of polymers. The methods that are already used in PET [poly(ethylene terephthalate)] recycling and the possibility of their extension to other types of polyesters are both shown.

Carbohydrates represent a promising option in transitioning from oil-based chemical resources to renewable ones, with the goal of developing chemistries for a sustainable future. Cellulose, hemicellulose, and largely available monosaccharides already provide useful chemical building blocks, so-called platform chemicals, such as levulinic acid and hydroxymethyl furfural, as well as solvents like cyrene or gamma-valerolactone. Therefore, there is great anticipation for novel applications involving materials and chemicals derived from sugars. In the field of ionic liquids (ILs), sugar-based ILs have been overlooked for a long time, mainly on account of their multistep demanding preparation. However, exploring new strategies for accessing sugar-based ILs, their study, and their exploitation, are attracting increasing interest. This is due to the growing concerns about the negative (eco)toxicity profile of most ILs in conjunction with their non-sustainable nature. In the present review, a literature survey concerning the development of sugar-based ILs since 2011 is presented. Their preparation strategies and thermal behavior analyses, sorted by sugar type, make up the first two sections with the intention to provide the reader with a useful guide. A final overview of the potential applications of sugar-based ILs and their future perspectives complement the present analysis.

New bis-quinolinium chiral ionic liquids (CILs) were synthesized in good yields starting from isomannide and isosorbide by a straightforward procedure that maintains the absolute stereostructure of the isohexide scaffolds. Thermal gravimetric analysis and differential scanning calorimetry, aimed at investigating the short thermal stability and the thermal behaviour of the synthesized ionic compounds are presented. The stereochemical features of both ionic derivatives and their neutral precursors were investigated by electronic circular dichroism (ECD) spectroscopy. ECD spectra of neutral compounds 5 and 6 and their N-methylated cations (5-Me+ and 6-Me+) were theoretically investigated by means of molecular modelling and excited-state calculations. A theoretical conformational analysis suggests the possible use of the isohexide derivatives as tweezers-type hosts in recognition processes toward different kinds of guests. Some of the ionic derivatives were successfully used in the NMR enantiorecognition of TFAE, discriminating the enantiomers through a tweezers-like mechanism.

We present an extension of our Molecular Transformer architecture combined with a hyper-graph exploration strategy for automatic retrosyn- thesis route planning without human intervention. The single-step ret- rosynthetic model sets a new state of the art for predicting reactants as well as reagents, solvents and catalysts for each retrosynthetic step. We introduce new metrics (coverage, class diversity, round-trip accuracy and Jensen-Shannon divergence) to evaluate the single-step retrosynthetic models, using the forward prediction and a reaction classification model always based on the transformer architecture. The hypergraph is con- structed on the fly, and the nodes are filtered and further expanded based on a Bayesian-like probability. We critically assessed the end-to-end framework with several retrosynthesis examples from literature and aca- demic exams. Overall, the frameworks has a very good performance with few weaknesses due to the bias induced during the training process. The use of the newly introduced metrics opens up the possibility to optimize entire retrosynthetic frameworks through focusing on the performance of the single-step model only.Available on IBM RXN for Chemistry: https://rxn.res.ibm.com.

Tolterodine (1) is a potent muscarinic receptor antagonist used in the treatment of overactive urinary bladder (OAB) syndrome. Tolterodine is chiral and it was patented, and is currently marketed, as the l-tartrate salt of the (R)-enantiomer. However, the existing literature does not offer an ultimate proof of a stereoselective mode of action of 1. A second open stereochemical issue concerns the absolute configuration (AC) of 1. Neither the original patents nor subsequent studies have established the AC of 1 in an unambiguous way, although the AC of the l-tartrate salt of 1 was assigned by X-ray diffractometry. Finally, neither electronic nor vibrational circular dichroism (ECD and VCD) spectra of 1 are reported so far. We performed a thorough ECD/VCD study of 1 in different solvents and at variable temperatures. Solvent and temperature dependence highlighted the existence of moderate flexibility which was confirmed by molecular modelling. ECD calculations with time-dependent density functional theory (TDDFT) accurately reproduced the experimental spectra and allowed us to confirm the AC of 1 in an independent way.

Chiral ionic liquids (CILs) have been obtained in high yield using commercial propylene oxide or natural alcohols (citronellol and nopol) as building blocks. The self-assembly ability at the interface IL/air for some couples of enantiopure and racemic CILs was explored by angle resolved XPS.

Chiral bis-amido phosphites L1 and L2 containing a diaminobiphenyl unit and a chiral alkoxy group derived from either (−)-menthol or 3-acetoxy deoxycholic methyl ester have been synthesised. Both L1 and L2 react with PdCl2(NCPh)2 affording di- or mononuclear derivatives with formula trans-[Pd(μ-Cl)Cl(L)]2 (1a, L = L1; 1b, L = L2) or trans-PdCl2(L)2 (2a, L = L1; 2b, L = L2) depending on the Pd : L molar ratio. The crystal structure of (M,P)-1a confirms the trans arrangement of the ligand L1 and shows an unusual puckering of the Pd2(μ-Cl)2 core (θ 46°). Both the ligands L1 and L2 and their complexes (1 and 2) are fluxional in solution as a consequence of the tropo-inversion of the diaminobiphenyl unit. For L1, L2, 1a and 2a a combined study including variable temperature 31P{1H} NMR spectroscopy and line shape analysis, Eyring plots and DFT calculations have shed light on the mechanism of the tropo-inversion., Financial support from the Ministerio de Economía y Competitividad (MINECO/FEDER) of Spain (Projects CTQ2013-42532-P and CTQ2016-75884-P), Diputación General de Aragón (DGA/FSE E07) and the University of Pisa is gratefully acknowledged. A. P. acknowledges financial support from the ERASMUS+ programme.

Chiral binaphthyl diamidophosphites derived from deoxycholic acid were synthesized and used as ligands for the preparation of mononuclear Pd(II) complexes, which were employed as catalysts in the asymmetric Suzuki-Miyaura cross-coupling of arylboronic acids with aryl bromides. Among the different reaction parameters, the substrate concentration emerged as being crucial for the outcome of the reaction: the reaction was faster in a concentrated reaction mixture, and could be performed at 0 °C, where the reaction promoted by the Pd-complexes was more enantioselective affording cross-coupling products with ee up to 70%., This work was supported by University of Pisa. Financial support from the Ministerio de Economía y Competitividad (MINECO/FEDER) of Spain (Projects CTQ2013-42532-P and CTQ2016-75884-P) and Diputación General de Aragón (DGA/FSE E07) is gratefully acknowledged.

Three different 2,2′-binaphthylphosphites were synthesized, starting from suitable derivatives of cholic or deoxycholic acids and 1,1′-dihydroxy-2,2′-binaphthyl, and their stereochemical features were analyzed by CD and NMR spectroscopy. The spectroscopic data clearly demonstrate the capability of the cholestanic backbone to induce a M prevalent screw sense to the flexible binaphthyl moiety, giving rise to tropos ligands. The extent of the prevalence of the M sense of twist depends on the position at which the binaphthylphosphite moiety is linked on the bile acid skeleton. The three phosphites were mixed with [Rh(COD)2][BF4] and the resulting complexes were analyzed by variable temperature 31P NMR spectroscopy, thereby obtaining information on their stereochemical characteristics, which reflect the different asymmetric induction capability of the ligands.

A tropos deoxcholic acid derived diamidophosphite was synthesised starting from deoxycholic acid and N,N′-dimethyl-2,2′-diamino-1,1′biphenyl and its stereodinamic characteristics were assessed by VT-NMR spectroscopy. The capability of the diamidophosphite to act as Rh-ligand was investigated in the formation of ionic as well as covalent Rh-complexes. The stereodinamic properties of these complexes were studied by VT-NMR spectroscopy.

The use of cholic acid derivative 1 , bearing a d -prolinamide moiety linked at the 12-position of cholic acid methylester, as an organocatalyst in the asymmetric aldol reaction of cyclic ketones and aromatic aldehydes, gave the corresponding aldol products in good yield and ee up to 98%. This organocatalyst has proven to be efficient both in water and in organic solvent, where it has been used with a 1% loading.

Three new deoxycholic acid-based 5,5′-substituted biphenylphosphites, 2 – 4 , were synthesized and their stereochemical features were examined by CD and NMR spectroscopy, which allowed us to determine the sense of twist of the substituted biphenyl moiety as well as the extent of its prevalence in different solvents. Phosphites 1 – 4 were used as chiral ligands in the copper catalyzed conjugate addition of diethylzinc to acyclic enones, affording the alkylation products with ees up to 65%. The results obtained allowed a correlation between asymmetric induction and the sense of twist of the biphenylphosphite moiety of the chiral inducers.

Two diastereoisomeric chiral stationary phases (CSPs), devised for enantioselective HPLC, showing unexplained differences in their chromatographic performances, have been characterized, together with their soluble models, by means of 13C-cross polarization/magic angle spinning (CP/MAS), 1H-MAS and 1H-free induction decay (FID) analysis. The NMR investigation of the soluble models has not highlighted significant structural/conformational differences between the two diastereoisomers, but has constituted a useful support for the analysis of the more complex NMR data of the CSPs. The organic chiral selectors of the stationary phases show a poor internal mobility and no conformational differences between the two diastereoisomers have been observed. On the contrary, interesting differences between the two CSPs have been found involving the silanols on the silica surface and the dynamics of the linking chains between the organic selectors and the silica surface itself. An explanation of the chromatographic behaviour has been proposed in terms of different proximity of the organic moieties with respect to the inorganic surface in the two CSPs.

A s-triazine scaffold bearing a free and a protected amino group was used for connecting two different chiral auxiliaries, whose enantiodiscriminating capabilities in enantioselective chromatography are well documented. A biselector system was synthesized and, after linkage to silica gel, used for the chromatographic resolution of different racemic analytes, chosen among the compounds resolved by the two different isolated chiral auxiliaries. The obtained chromatographic results were compared with literature data related to the use of the two chiral stationary phases (CSPs) whose chiral moieties constitute the biselector CSP, allowing us to gain useful information about potentialities and limitations of this approach for obtaining independent CSPs having broader applicability with respect to the classical independent monoselector CSPs. Copyright © 2005 John Wiley & Sons, Ltd.

Four phosphites, obtained by linking enantiomerically pure binaphthylchlorophosphite to the two different hydroxy substituted positions of deoxycholic acid, were used as chiral ligands in the enantioselective copper catalysed 1,4-addition of diethylzinc to 2-cyclohexenone and dimethylzinc to 2-cyclopentadecenone. Various reaction parameters were changed in order to select the experimental conditions that would maximise yield and ee. The four ligands were screened for activity and enantioselectivity under the optimised reaction conditions for comparative purposes, in order to establish the influence of the absolute configuration of the binaphthyl moiety as well as the position on the cholestanic backbone of the phosphite moiety. The ligand possessing a ( R )-binaphthylphosphite moiety at position 12 of the cholestanic backbone proved to be the most enantioselective affording (−)-( R )-muscone in 63% ee.

The use of chiral stationary phases (CSPs) obtained from cholic and deoxycholic acid derivatives in the HPLC resolution of racemic compounds is presented. The CSPs containing arylcarbamoyl derivatives of bile acids show enantiodiscriminating capabilities depending on the electronic character of the aryl substituents: the CSPs obtained starting from heteroderivatized selectors, i.e. bile acid derivatives containing both π-acidic and π-basic arylcarbamoyl moieties, show enantiodiscriminating capabilities strongly dependent on the arrangement of the electronically different arylcarbamates on the cholestanic backbone. The CSPs obtained starting from deoxycholic acid derivatives possessing both arylamido and arycarbamoyl substituents show enantiodiscriminating capabilities restricted to the resolution of benzodiazepine derivatives. Again, the enantioresolution properties depend not only on the electronic nature of the aromatic substituents but also on their arrangement on the cholestanic backbone. The comparison among the different families of bile acid based CSPs allows us to find likeness and differences in the enantiorecognition mechanism exhibited by the different chiral selectors.

An s-triazine scaffold bearing a free and a protected amino group was synthesised and used for connecting two different and differently derivatised aminoacids. Two diastereoisomeric chiral systems were obtained and, once linked to silica gel, they were used in the chromatographic resolution of structurally and electronically different racemic analytes, chosen among the racemates resolved by the isolated aminoacid derivatives. The collected results demonstrate the biselector behaviour of the CSPs in terms of enantiodiscriminating capability towards the class of racemic compounds resolved by both the isolated selectors as well as in terms of the independent action of the two chiral moieties of the system.

A number of chiral 1,10-phenanthrolines (phens) have been assessed in asymmetric Cu(I)-catalyzed allylic oxidation of cyclohexene. Very effective copper-phen catalysts are obtained only when these ligands bear at least a substituent close to the reactive site of the catalyst. Enantioselectivity up to 36% was obtained.

Optically active 1-(1-naphthyl)ethylamine, N -3,5-dinitrobenzoylphenylglycine and N -3,5-dinitrobenzoylleucine were used as chiral building blocks to prepare three new enantiomerically pure bifunctional chiral auxiliaries for enantioselective HPLC, belonging to a family of biselector systems, the first example of which ( CSP1 ) has been described previously. These compounds were covalently linked to silica gel to produce three chiral stationary phases ( CSPs 2 – 4 ), whose enantiodiscriminating capability towards the HPLC resolution of selected racemic compounds was assessed. The obtained results allowed us to establish the influence of the stereochemistry and/or the chemical structure of each chiral moiety of the biselector system on their enantiorecognition properties.

Four new chiral selectors, obtained by derivatising the hydroxy groups of cholic acid with 2-naphthylisocyanate and 3,5-dinitrophenylisocyanate have been prepared and linked to silica gel to obtain new chiral stationary phases (CSPs) for the HPLC separation of enantiomers. The CSP containing only 2-naphthylcarbamate groups is able to separate the enantiomers of π-acidic substrates, whereas the CSPs containing one 3,5-dinitrophenylcarbamate group and two 2-naphthyl carbamate moieties resolve π-acidic racemic compounds as well as π-basic substrates, with the observed enantiodiscriminating capabilities depending on the arrangement of the different carbamoyl units on the cholestanic backbone.