Correlated rotations in benzylfluorene derivatives: structure, conformation, and stereodynamics

Fluorene derivatives, having substituted benzyl groups bonded to position 9, have been investigated by variable temperature NMR spectroscopy. Stereodynamic processes involving restricted rotation about the fluorenyl-CH2 and aryl-CH2 bonds have been observed, leading to conformers and enantiomeric forms, and the corresponding barriers were determined by line shape simulation. These dynamic processes are interpreted as being due to correlated rotation pathways, on the basis of DFT computations that satisfactorily reproduce the experimental barriers. The structures of two such compounds were also determined by single-crystal X-ray diffraction.     

Acyl migration from N to C in aziridine-2-carboxylic esters

Acyl group migration from N to C in aziridine-2-carboxylates takes place in deprotonation reactions and, as a result, aziridine-2,2-dicarboxylates are formed. Mechanistic studies proved that the observed migration is an intramolecular reaction.     

Structural Aspects of the O-glycosylation Linkage in Glycopeptides via MD Simulations and Comparison with NMR Experiments

A powerful conformational searching and enhanced sampling simulation method, and unbiased molecular dynamics simulations have been used along with NMR spectroscopic observables to provide a detailed structural view of O-glycosylation. For four model systems, the force-field parameters can accurately predict experimental NMR observables (J couplings and NOE's). This enables us to derive conclusions based on the generated ensembles, in which O-glycosylation affects the peptide backbone conformation by forcing it towards to an extended conformation. An exception is described for β-GalNAc-Thr where the α content is increased and stabilized via hydrogen bonding between the sugar and the peptide backbone, which was not observed in the rest of the studied systems. These observations might offer an explanation for the evolutionary preference of α-linked GalNAc glycosylation instead of a β link.     

Acceleration of arylzinc formation and its enantioselective addition to aldehydes by microwave irradiation and aziridine-2-methanol catalysts

The formation and 2-amino alcohol catalyzed addition of arylzinc reagents from and with boronic acids, respectively, is drastically accelerated to a few minutes under microwave irradiation without loss of enantioselectivity (up to 98% ee). Of the amino acid derived catalysts tested, the conformationally restricted bulky substituted aziridine-2-methanols derived from serine show the best overall performance in the formation of diarylmethanols.     

Serinolic amino-s-triazines: iterative synthesis and rotational stereochemistry phenomena as N-substituted derivatives of 2-aminopropane-1,3-diols

The iterative synthesis of 2,4,6-triamino-s-triazines (melamines), precursors and dendritic structures, by amination of cyanuric chloride with C-1 versus C-2-substituted 2-aminopropane-1,3-diols (serinols), is comparatively examined. The stereochemistry of the resulting serinolic amino-s-triazines, issued from the restricted rotation about the newly created C(s-triazine)-N bonds, is for the first time discussed in terms of (pro)diastereomerism based on DNMR and DFT calculation data.     

Synthesis of optically active amphiphilic tetrathiafulvalene derivatives

The synthesis and characterization of novel chiral tetrathiafulvalenes bearing two long alkyl chains at one end of the π-electron rich unit and different functional groups—ester, acid or thiolate—at the other extreme is described. The synthetic method requires the preparation of 1,3-dithiol derivatives with two stereogenic centers. Different routes and reaction conditions were explored to form these compounds, whose optimized synthesis involved the nucleophilic substitution of a chiral bromo methylene derivative with tetrabutylammonium bis(2-thioxo-1,3-dithiole-4,5-dithiolate)zincate. The tetrathiafulvalenes were prepared by coupling the 1,3-dithiol derivative with 4,5-bis(methoxycarbonyl)-1,3-dithiol-2-one or 4,5-bis(2-cyanotehylthio)-1,3-dithiol-2-thione. The products were fully characterized, including by circular dichroism spectroscopy, which confirmed their optical activity. They are promising candidates to be used as building blocks in supramolecular materials for molecular electronics, to produce systems with unique electrical, magnetic or optical properties that stem from their chirality.     

Carbohydrate–Arene Interactions Direct Conformational Equilibrium of a Flexible Glycophane in Water

Water, the flexibility of the maltose molecule , and sugar/arene interactions are responsible for the equilibrium between a folded ( I ) and nonfolded ( II ) conformation in a glycophane ( III is an intermediate). Glycophanes are cyclodextrin–cyclophane hybrids, which are of interest as models of receptors.     

Theoretical studies and NMR assay of coumarins and neoflavanones derivatives as potential inhibitors of acetylcholinesterase

Currently Alzheimer's disease (AD) is a devastating neurological disorder that mainly affects the elderly. The treatment of AD has as main objective to increase the levels of ACh in the synaptic cleft by inhibiting the cholinesterase enzymes, which are responsible for the degradation of ACh. Twenty one synthesized coumarins and neoflavanones (4-arylcoumarins) and theoretical studies were used to select the most promising ligands for in vitro experimental studies by Nuclear Magnetic Resonance. The eight compounds selected for the experimental study only 12b (effectiveness 68.54 ± 3.22%) was promising AChE inhibitor. This compound (12b) presents substituents at positions 4, 5, 6, 7 and 8 in a coumarin nucleus, being the most significant characteristic in comparison to the other studied compounds. These results can be used for the design and synthesis of other possible derivatives with inhibitory potential of AChE.     

New Organophosphorus Proligands and Amide Precursors: Crystal and Molecular Structures of Ph2P(X)NH(C6H3Pri 2-2,6) (X = O,S) and (OPPh2)(O2SMe)N(C6H3Pri 2-2,6)

The new organophosphorus proligand (OPPh₂)(O₂SMe)NR (R = C₆H₃Prⁱ ₂–2,6) (3) was prepared as a white crystalline solid by reacting the lithiated compound Li[Ph₂P(O)NR] with MeSO₂Cl in a 1:1 molar ratio. The precursor Ph₂P(O)NHR (1), as well as its thio analogue Ph₂P(S)NHR (2), were obtained in the reaction between the lithiated amine RNHLi and the corresponding organophosphorus chloride. All compounds were characterized by multinuclear (¹H, ¹³C, and ³¹P) NMR spectroscopy. The molecular structures of 1–3 were established by single-crystal X-ray diffraction. A zigzag polymeric chain is formed in the crystals of 1 and 2 by hydrogen N–H···X (X = O, S) bonding, while the crystal of 3 contains discrete monomeric units with a syn–syn conformation of the O?P(C)₂–N–S(C)(?O)₂ skeleton.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Relative stereochemical assignment of C-33 and C-35 in the antibiotic gladiolin

Gladiolin is a macrolide antibiotic isolated from Burkholderia gladioli BCC0238 with promising activity against Mycobacterium tuberculosis, including several multidrug resistant strains. The configuration of all but one of the stereogenic centers of gladiolin has previously been elucidated using a combination of NOESY NMR experiments and predictive sequence analysis of the polyketide synthase responsible for its assembly. However, it was not possible to assign the configuration of the C-35 methyl group using such methods. Here we report the synthesis of C-33/C-35-syn and C-33/C-35-anti mimics of the C-30 to C-38 fragment of gladiolin from (R) and (S)-citronellol, respectively. Comparison of HSQC NMR data for the mimics and the natural product showed that the C-35 methyl is anti to the C-33 hydroxyl group, indicating that gladiolin has the 35S configuration.     

Reactions of aziridine-2-carboxylic acid derivatives with aldehydes and ketones

The reaction of methyl aziridine-2-carboxylate with hydrazine or alkylhydrazines gives the respective hydrazides, which with ketones form 2,2-disubstituted 1,3,4-triazabicyclo-[4.1.0] heptan-5-ones. With aldehydes they form the respective hydrazones. The reaction of the amide and methyl ester of aziridine-2-carboxylic acid with aldehydes gives a series of aziridinocarbinols.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 774–778, June, 1985.     

Conformational and receptor-binding properties of the insect neuropeptide proctolin and its analogues

Summary Proctolin (Arg-Tyr-Leu-Pro-Thr) was the first insect neuropeptide to be chemically characterised. It plays an essential role in insect neurophysiology and is involved in muscular contraction and neuromodulation. Elements of secondary structure in solution have been studied by comparing data obtained from NMR and molecular dynamics simulations. Different secondary structural requirements are associated with agonist and antagonist activities. A favoured conformation of proctolin has an inverse -turn, comprising an intramolecular hydrogen bond near the C-terminal end between Thr NH and Leu CO. Antagonists have a more compact structure resembling a paperclip loop, containing an intramolecular hydrogen bond between Tyr NH and Pro CO, possibly stabilised by a salt bridge between the N- and C-terminal groups. A cyclic analogue retains antagonist activity and resembles a -bulge loop, also comprising intramolecular hydrogen bonds between Tyr NH and Pro CO and Thr CO. These models may offer feasible starting points for designing novel compounds with proctolinergic activity.     

Asymmetric synthesis of alpha-methylphosphophenylalanine derivatives using sulfinimine-derived enantiopure aziridine-2-phosphonates

[formula: see text] 2-Methylaziridine-2-phosphonates were prepared from enantiopure sulfinimines and were demonstrated to be versatile synthetic intermediates for the synthesis of novel alpha-disubstituted and alpha,beta-trisubstituted alpha-aminophosphonate derivatives. The first asymmetric synthesis of both enantiomers of alpha-methylphosphophenylalanine is described.     

Non-biaryl atropisomers derived from carbohydrates. Part 4: Absolute stereochemistry of carbohydrate-based imidazolidine-2-ones and 2-thiones with axial and central chirality

NMR spectroscopy has proven to be an enabling methodology in elucidating the axial chirality of a series of non-biaryl atropisomers attached to a carbohydrate moiety, based on deshielding effects caused by the aromatic ring.     

Quantum control of a chiral molecular motor driven by femtosecond laser pulses: Mechanisms of regular and reverse rotations

Rotational mechanisms of a chiral molecular motor driven by femtosecond laser pulses were investigated on the basis of results of a quantum control simulation. A chiral molecule, (R)-2-methyl-cyclopenta-2,4-dienecarboaldehyde, was treated as a molecular motor within a one-dimensional model. It was assumed that the motor is fixed on a surface and driven in the low temperature limit. Electric fields of femtosecond laser pulses driving both regular rotation of the molecular motor with a plus angular momentum and reverse rotation with a minus one were designed by using a global control method. The mechanism of the regular rotation is similar to that obtained by a conventional pump–dump pulse method: the direction of rotation is the same as that of the initial wave packet propagation on the potential surface of the first singlet (nπ^*) excited state S₁. A new control mechanism has been proposed for the reverse rotation that cannot be driven by a simple pump–dump pulse method. In this mechanism, a coherent Stokes pulse creates a wave packet localized on the ground state potential surface in the right hand side. The wave packet has a negative angular momentum to drive reverse rotation at an early time.     

Absolute configuration of diastereomeric derivatives of N-substituted aziridine-2-carboxylic acids

Individual diastereomers of a number of anilides of N-substituted aziridine-2-carboxylic acids have been obtained. Conclusions regarding the spatial structure of the compounds indicated have been drawn on the basis of the ¹H NMR, ¹⁵N NMR, and CD spectra.Report 37 of the series entitled Asymmetric nonbridging nitrogen. For report 36 see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1343–1348, October, 1984.     

The Role of Conformations in the Interplay of Structure and Dynamics in Macromolecular and Supramolecular Systems

Summary: Following Paul J. Flory, the role of local chain conformation in determining the structure and dynamics of macromolecules is elucidated, employing advanced solid state NMR spectroscopy supported by X-ray scattering and dielectric spectroscopy. Topics covered include the local conformation in amorphous polymers, conformational memory, chain organization and dynamics in semicrystalline polymers, polypeptides, and rod-coil copolymers.     

New receptors for anions in water: Synthesis, characterization, X-ray structures of new derivatives of 5,11,17,23-tetraamino-25,26,27,28-tetrapropyloxycalix[4]arene

Syntheses and characterization of ten new compounds from the calixarene family, cone - 5,11,17,23- tetrakis(2-pyridylmethylamino)-25,26,27,28-tetrapropyloxycalix[4]arene 4a; cone - 5,11,17,23-tetrakis(3-pyridylmethylamino)-25,26,27,28-tetrapropyloxycalix[4]arene 4b; cone - 5,11,17,23-tetrakis(4-pyridylmethylamino)-25,26,27,28-tetrapropyloxycalix[4]arene 4c; cone - 5,11,17,23-tetrakis(ferrocenylmethylamino)-25,26,27,28-tetrapropyloxycalix[4]arene 4d; cone - 5,11,17,23-tetrakis(2-pyridylmethimino)-25,26,27,28-tetrapropyloxycalix[4]arene 3a; cone - 5,11,17,23-tetrakis(3-pyridylmethimino)-25,26,27,28-tetrapropyloxycalix[4]arene 3b; cone - 5,11,17,23-tetrakis(4-pyridylmethimino)-25,26,27,28-tetrapropyloxycalix[4]arene 3c; cone - 5,11,17,23-tetrakis(ferrocenylmethimino)-25,26,27,28-tetrapropyloxycalix[4]arene 3d; cone - 5,11,17,23-tetrakis(2-thienylmethimino)-25,26,27,28-tetrapropyloxycalix[4]arene 3e and cone - 5,11,17,23-tetrakis(2-pyrrolylmethimino)-25,26,27,28-tetrapropyloxycalix[4]arene 3f are reported. The target compounds 4a-4d were designed to form complexes with anions based on hydrogen bonds and electrostatic interactions in acidic aqueous solutions and the interaction constant 1770 mol⁻¹ dm³ of a 1:1 complex was obtained for the interaction of 4c with sulfate anion in 5 × 10⁻³ M aqueous HCl. The solid state structures of the compounds 3b, 3e and 3f were determined, their stereochemistry and the stereochemistry of the calix[4]arene frame is generally discussed. Raman, infrared and UV-vis spectra of the target compounds and some intermediates are reported, too.     

Studies on molecular mechanism between SHP2 and pyridine derivatives by 3D-QSAR,molecular docking and MD simulations

BackgroundSrc homology 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2) as a major phosphatase would affect the development of tumors by regulating several cellular processes, and is a significant potential target for cancer treatment.MethodsIn the present work, a series of pyridine derivatives possessing a wide range of inhibitory activity was employed to investigate the structural requirements by developing three dimensional quantitative structure–activity relationship (3D-QSAR) models using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods. The results show that CoMFA (R²_cv = 0.646, R²_pred = 0.5587) and CoMSIA (R²_cv = 0.777, R²_pred = 0.7131) have excellent stability and predictability. The relationship between the inhibitory activity and structure of the inhibitors was analyzed by the derived contour maps. Furthermore, the QSAR models were validated by molecular docking and molecular dynamics simulations, which were also applied to reveal the potential molecular mechanism of these inhibitors.FindingsIt was found that Arg110, Asn216, Thr218, Thr252 and Pro490 play a crucial role in stabilizing the inhibitors. Additionally, MM/PBSA calculations provided the binding free energy were also conducted to explain the discrepancy of binding activities. Overall, the outcomes of this work could provide useful information and theoretical guidance for the development of novel and potent SHP2 inhibitors.