Systematic, computational discovery of multicomponent and one-pot reactions.

Discovery of new types of reactions is essential to organic chemistry because it expands the scope of accessible molecular scaffolds and can enable more economical syntheses of existing structures. In this context, the so-called multicomponent reactions, MCRs, are of particular interest because they can build complex scaffolds from multiple starting materials in just one step, without purification of intermediates. However, for over a century of active research, MCRs have been discovered rather than designed, and their number remains limited to only several hundred.

Machine Learning Algorithm Guides Catalyst Choices for Magnesium-Catalyzed Asymmetric Reactions.

Organic-chemical literature encompasses large numbers of catalysts and reactions they can effect. Many of these examples are published merely to document the catalysts' scope but do not necessarily guarantee that a given catalyst is "optimal"-in terms of yield or enantiomeric excess-for a particular reaction. This paper describes a Machine Learning model that aims to improve such catalyst-reaction assignments based on the carefully curated literature data.

Computational prediction of complex cationic rearrangement outcomes.

Recent years have seen revived interest in computer-assisted organic synthesis. The use of reaction- and neural-network algorithms that can plan multistep synthetic pathways have revolutionized this field, including examples leading to advanced natural products. Such methods typically operate on full, literature-derived 'substrate(s)-to-product' reaction rules and cannot be easily extended to the analysis of reaction mechanisms.

Modified glucose as a sensor to track the metabolism of individual living endothelial cells - Observation of the 1602 cm band called "Raman spectroscopic signature of life".

A relatively new approach to subcellular research is Raman microscopy with the application of sensors called Raman probes. This paper describes the use of the sensitive and specific Raman probe, 3-O-propargyl-d-glucose (3-OPG), to track metabolic changes in endothelial cells (ECs). ECs play a significant role in a healthy and dysfunctional state, the latter is correlated with a range of lifestyle diseases, particularly with cardiovascular disorders.

Changes in the mitochondrial membrane potential in endothelial cells can be detected by Raman microscopy.

The role of mitochondria goes beyond their capacity to create molecular fuel and includes e.g. the production of reactive oxygen species and the regulation of cell death.

EdU sensing: The Raman way of following endothelial cell proliferation in vitro and ex vivo.

Endothelial cells line the lumen of all vessels in the body and maintain vascular homeostasis. In particular, endothelial cell regeneration in response to insult sustain functional endothelial layer. EdU (5-ethynyl-2'-deoxyuridine) is an alkyne-tagged proliferation probe that incorporates into newly synthesized DNA and is used for fluorescence imaging of cell proliferation with the use of "click chemistry" reaction with a fluorescent azide.

Propargylation of CoQ0 through the Redox Chain Reaction.

An efficient catalytic propargylation of CoQ0 is described by employing the cooperative effect of Sc(OTf) and Hantzsch ester. It is suggested to work through the redox chain reaction, which involves hydroquinone and dimeric propargylic moiety intermediates. A broad range of propargylic alcohols can be converted into the appropriate derivatives of CoQ0 containing triple bonds in good to excellent yields.

Nicotinamide N-methyltransferase in endothelium protects against oxidant stress-induced endothelial injury.

Nicotinamide N-methyltransferase (NNMT, EC 2.1.1.

Multiplex Raman imaging of organelles in endothelial cells.

Raman imaging using molecular reporters is a relatively new approach in subcellular investigations. It enables the visualization of organelles in cells with better selectivity and sensitivity compared to the label-free approach. Essentially Raman reporters possess in their structure an alkyne molecular group that can be selectively identified in the spectral region silent for biomolecules, hence facilitate the localization of individual organelles.

Computational planning of the synthesis of complex natural products.

Training algorithms to computationally plan multistep organic syntheses has been a challenge for more than 50 years. However, the field has progressed greatly since the development of early programs such as LHASA, for which reaction choices at each step were made by human operators. Multiple software platforms are now capable of completely autonomous planning.

Correction to: Comparative Assessment of the New PDE7 Inhibitor - GRMS-55 and Lisofylline in Animal Models of Immune-Related Disorders: A PK/PD Modeling Approach.

There was a mistake in the unit of clearance (Cl) in Table II. In addition, the descriptions of V and V were imprecise and the reference number in the footnote below this table should be (9). The corrected Table appears below.

Comparative Assessment of the New PDE7 Inhibitor - GRMS-55 and Lisofylline in Animal Models of Immune-Related Disorders: A PK/PD Modeling Approach.

Purpose: This study aimed to assess the activity of two phosphodiesterase (PDE) inhibitors, namely GRMS-55 and racemic lisofylline ((±)-LSF)) in vitro and in animal models of immune-mediated disorders.

Methods: Inhibition of human recombinant (hr)PDEs and TNF-alpha release from LPS-stimulated whole rat blood by the studied compounds were assessed in vitro. LPS-induced endotoxemia, concanavalin A (ConA)-induced hepatitis, and collagen-induced arthritis (CIA) animal models were used for in vivo evaluation.

Chiral Amplification in Nature: Studying Cell-Extracted Chiral Carotenoid Microcrystals via the Resonance Raman Optical Activity of Model Systems.

Carotenoid microcrystals, extracted from cells of carrot roots and consisting of 95 % of achiral β-carotene, exhibit a very intense chiroptical (ECD and ROA) signal. The preferential chirality of crystalline aggregates that consist mostly of achiral building blocks is a newly observed phenomenon in nature, and may be related to asymmetric information transfer from the chiral seeds (small amount of α-carotene or lutein) present in carrot cells. To confirm this hypothesis, we synthesized several model aggregates from various achiral and chiral carotenoids.

Asymmetric total synthesis of (+)-asenapine.

Asymmetric total synthesis of (+)-asenapine, an atypical antipsychotic drug, used for treating schizophrenia and acute mania associated with bipolar disorder, is reported. The key steps are the organocatalytic Michael addition of aldehydes to trans-nitroalkenes and subsequent reductive cyclization.

Influence of inflammatory disorders on pharmacokinetics of lisofylline in rats: implications for studies in humans.

1. Despite the number of favourable properties of lisofylline (LSF), clinical trials on this compound have not yielded the expected results yet. 2.

Intramolecular Tandem Seleno-Michael/Aldol Reaction: A Simple Route to Hydroxy Cyclo-1-ene-1-carboxylate Esters.

Intramolecular tandem seleno-Michael/aldol reaction followed by an oxidation-elimination process can be an efficient tool for the construction of hydroxy cyclo-1-ene-1-carboxylate esters from oxo-α,β-unsaturated esters. Generation of lithium selenolate from elemental selenium and n-BuLi provides a simple and efficient one-pot access to cyclic endo-Morita-Baylis-Hillman adducts.

Stereocontrolled synthesis of oleanolic saponin ladyginoside A isolated from Ladyginia bucharica.

Efficient stereocontrolled synthesis of ladyginoside A isolated from Ladyginia bucharica is described. The presented methodology bases on the β-selective glycosylation to construct oleanate-3-O-β-glycoside from selectively protected d-cellobiose comprising desired β-linkage in carbohydrate unit. By using this procedure, dimethyl ester of ladyginoside A (1) (methyl oleanate 3-O-(β-d-glucopyranosyl)-(1 → 4)-β-d-glucuronide methyl ester) was obtained in 16% overall yield.

Total synthesis of pipecolic acid and 1-C-alkyl 1,5-iminopentitol derivatives by way of stereoselective aldol reactions from (S)-isoserinal.

A short synthesis of iminosugars and pipecolic acid derivatives has been realized through aldol addition of a pyruvate, a range of ketones and (S)-isoserinal, followed by catalytic reductive intramolecular amination. The stereoselective aldol reaction was achieved successfully by using tertiary amines or di-zinc aldol catalysts, thus constituting two parallel routes to optically pure products with good yields and high diastereoselectivities. These carbohydrate analogues may be the inhibitors of potent glycosidases and glycosyltransferases.

Application of the EF and GH Fragments to the Synthesis of Idraparinux.

A novel total synthesis of fully protected idraparinux has been achieved. A short and efficient protocol for the synthesis of the EF fragment of idraparinux and its C5'-epi analogue (GH unit) has been developed. The same cellobiose unit was transformed in 14 steps into the fully protected EF and GH disaccharide fragments.

Iron-Catalyzed Asymmetric Nitro-Mannich Reaction.

The first enantioselective addition of nitroalkanes to imines (nitro-Mannich reaction), mediated by an iron(II) catalyst assembled by a hindered hydroxyethyl-pybox ligand, is described. This valuable carbon-carbon bond-forming reaction proceeds smoothly at room temperature to afford enantioenriched β-nitro amines in good yields and high enantioselectivity, up to 98% with unprecedentedly low iron catalyst loading (5 mol %).

PK/PD studies on non-selective PDE inhibitors in rats using cAMP as a marker of pharmacological response.

In recent years, phosphodiesterase (PDE) inhibitors have been frequently tested for the treatment of experimental inflammatory and immune disorders. It is suggested that anti-inflammatory properties of PDE inhibitors are related to their ability to increase cAMP levels. The aim of this study was to verify the hypothesis that cAMP may be a useful marker of pharmacological response following administration of non-selective PDE inhibitors (pentoxifylline and (±)-lisofylline) to endotoxemic rats.

Self-Enhancement of Rotating Magnetocaloric Effect in Anisotropic Two-Dimensional (2D) Cyanido-Bridged Mn-Nb Molecular Ferrimagnet.

The rotating magnetocaloric effect (RMCE) is a new issue in the field of magnetic refrigeration. We have explored this subject on the two-dimensional (2D) enantiopure {[Mn(R-mpm)][Nb(CN)]}·4HO (where mpm = α-methyl-2-pyridinemethanol) coordination ferrimagnet. In this study, the magnetic and magnetocaloric properties of single crystals were investigated along the bc//H easy plane and the a*//H hard axis.

Synthesis of l-Pyranosides by Hydroboration of Hex-5-enopyranosides Revisited.

Extensive study of the diastereoselective synthesis of l-pyranosides utilizing hydroboration of substituted exo-glucals (5-enopyranosides) obtained from d-sugars is presented. On the basis of this study we present the empirical rules describing the reaction stereoselectivity and the correlation between the yield of the l-ido product and the size of protecting groups used. Application of these guidelines revealed that the hydroboration of methyl 2,3-O-methyl-6-deoxy-α-d-xylo-hex-5-enopyranoside resulted in exclusive formation of l-ido product with high yield.

Synthesis of 2-Keto-d- and l-gluconic Acid via Stereoselective Direct Aldol Reactions.

Stereoselective direct aldol reaction between optically pure d- or l-glyceraldehyde and hydroxyacetylfuran is demonstrated as an efficient and straightforward methodology for the synthesis of six-carbon atom d- and l-arabino-hex-2-ulosonic acids. syn-Selective aldol reactions realized by using either tertiary amines or a dizinc aldol catalyst constitute two parallel routes to the de novo synthesis of orthogonally protected biologically relevant 2-keto-d- and l-gluconic acids.

Organocatalytic Synthesis of Higher-Carbon Sugars: Efficient Protocol for the Synthesis of Natural Sedoheptulose and d-Glycero-l-galacto-oct-2-ulose.

Herein we report a short and efficient protocol for the synthesis of naturally occurring higher-carbon sugars-sedoheptulose (d-altro-hept-2-ulose) and d-glycero-l-galacto-oct-2-ulose-from readily available sugar aldehydes and dihydroxyacetone (DHA). The key step includes a diastereoselective organocatalytic syn-selective aldol reaction of DHA with d-erythrose and d-xylose, respectively. The methodology presented can be expanded to the synthesis of various higher sugars by means of syn-selective carbon-carbon-bond-forming aldol reactions promoted by primary-based organocatalysts.