Conformational Fixation Research Articles

Enhancing the catalytic activity of 4-(dialkylamino)pyridines by conformational fixation.

Six times more active than DMAP (1), the tricyclic DMAP analogue 2 catalyzes the acetylation of a tertiary alcohol with acetic anhydride. The experimental results can be rationalized by quantum chemical calculations.

Mimicking the Biologically Active Part of the Cyclopeptides Segetalin A and B by “Clipping” of a Linear Tripeptide Derivative by Metal Coordination

A new method for the conformational fixation of bioactive loop-type peptide structures is presented. Hereby, ligand moieties are attached to the termini of a linear peptide sequence. Upon metal complexation, a macrocyclic structure with a loop-type conformation of the peptide is formed. As a representative example, the preparation of a WAG-bridged dicatechol derivative is described which mimics the active part of the natural products Segetalin A and Segetalin B.

Regio- and stereoisomeric control of the aggregation of zinc-chlorins possessing inverted interactive hydroxyl and carbonyl groups.

As models for a self-aggregative, naturally occurring magnesium-chlorin bacteriochlorophyll-d possessing 3(1)-secondary alcoholic hydroxyl and 13(1)-oxo groups, zinc-chlorins were synthesized with 3(1)-oxo and 13(1)-secondary (1) or tertiary hydroxyl groups (2). Compared to the monomers in a tetrahydrofuran solution, diastereomers 13(1)R-1R and 13(1)S-1S gave red-shifted absorption maxima (643 --> 674 nm in 1R and 708 nm in 1S) in 1 v/v% CH(2)Cl(2)-hexane solution, indicating their self-aggregation. Therefore, the positioning of the two groups at 3(1)/13(1) or 13(1)/3(1) on the N21-N23 molecular (Q(y)) axis is not necessarily important for the self-aggregation. The (1)H NMR and CD spectroscopic studies showed that the 674 nm absorbing species of 1R was characterized as a face-to-face "closed" dimer, while the 708 nm absorbing species of 1S was a large oligomer constructed with aggregation of head-to-tail "open" dimers. This diastereomeric control over the aggregation of 1R and 1S is more pronounced than that observed in the regioisomerically 3(1)-secondary alcoholic R/S-diastereomers 3R and 3S. The difference is ascribable to the conformational fixation of the 13(1)-hydroxyl group of the exo five-membered ring in 1. In contrast to self-aggregative 3(1)-tertiary alcoholic 4, both 13(1)-epimers of 13(1)-tertiary alcoholic 2 were monomeric even in nonpolar organic media: the additional 13(1)-methyl group (1 --> 2) drastically suppressed the self-aggregation due to the interference of the methyl group in intermolecular pi-pi interaction.

ChemInform Abstract: Synthesis of Artificial Nucleic Acids Functionalized by Fixation of Conformation

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Medium-sized cyclophanes. Part 53.1 Synthesis and conformational studies, and photoinduced cyclization of syn-[n.2]metacyclophanenes

A series of [n.2]metacyclophanenes (3) and (6) were prepared in good yields by a McMurry cyclization of 1,n-bis(3-acetyl-4-methoxyphenyl)alkanes (2) and 1,3-bis(3-formyl-4-methoxyphenyl)propane (5), respectively. Compounds 3b, 3c exist in the syn-conformation due to the steric repulsion between the methyl groups at the ethano bridge and the methoxy groups at the aromatic rings while compound 6 prefers the anti-conformation typical of [3.2]metacyclophanes. The assignment of syn-conformations has been confirmed by 1H NMR analyses and X-ray diffraction studies. Photoinduced transannular cyclization of [n.2]metacyclophanenes (3) and (6) in the presence of iodine as an oxidant afforded phenanthrene-anellated polycyclic aromatic hydrocarbons. Apparently, the rate of the photocyclization of anti-6 was found to be much faster than that of syn-3b and almost completed within 1 h. Thus, the different reactivities for the irradiation of syn- and anti-conformer were observed. The reason for the present preference for the formation of trans-dihydrophenanthrene rather than cis-dihydrophenanthrene as the intermediate might be attributable to the more stable chair form transition state than boat one and the conformational fixation to the chair form in the ground and transition state is possible in the anti-conformer.Key words: cyclophanes, strained molecule, McMurry reaction, C—C coupling, conformation analysis, cyclizations, photolysis, transannular reactions, transition states.

Chiral discrimination of methyl phenyl sulfoxide using dirhodium complexes

The potential of various chiral dirhodium complexes to discriminate racemic methyl phenyl sulfoxide is demonstrated by 1H and 13C NMR spectroscopy. Complexation occurs via a HOMO–LUMO interaction. Extraordinarily large signal dispersions (Δν) are observed with Rh2(mandelate)4. This can be rationalized by a conformational fixation of the sulfoxide by intramolecular hydrogen bonding. Copyright © 2000 John Wiley & Sons, Ltd.

Stereocontrolled Photooxygenations–A Valuable Synthetic Tool

The stereochemical course of the singlet-oxygen ene reaction with acyclic olefins may be controlled if in the substrate conformational fixation (1,3-allylic strain) an allyl-ic substituent for interaction with the attacking oxygen enophile aligns. Various substrates were chosen to elucidate the features of the olefin that are necessary to control the sense (threo versus erythro) and the extent of the ii-facial preference of the singlet-oxygen attack. Depending on the electronic properties of the double bond and the nature of the allylic substituent, threo or erythro selectivity may be imposed through hydrogen bonding, electrostatic and steric effects and stereoelectronic alignment. Such directing properties, especially that of the hydroxy group, were also confirmed in the other reaction modes of singlet oxygen, namely the [4+2] cycloaddition to chiral naphthylenic alcohols and the [2+2] cycloaddition to an adamantylidene-substituted allylic alcohol. The syntheses of the natural products Merucathin and Iso-dihydromahubanolide B are two examples in which such stereocontrolled photooxygenations have been used as key steps to build up the required chirality diastereose-lectively.

Inter-Peptide Hydrogen Bonding in Monolayers of Oligoglycine Amphiphiles

Abstract N-Octadecanoyl oligoglycine (monomer to pentamer) ethyl esters were synthesized. The structures of their monolayers and LB films transferred from pure water were investigated by π–A isotherms and FT-IR reflection absorption spectroscopy (FT-IR, RAS). All the glycine residues were involved in intermolecular hydrogen bonding as indicated by shifts of the NH stretching band and other IR features. The strength of the hydrogen bonds was increased with increasing numbers of the glycine residues in a molecule. The FT-IR characteristics of these monolayers are close to those of polyglycine II, despite the fact that these oligopeptides are not long enough for conformational fixation in bulk water.

非キレート配座規制を基盤とする含窒素天然物のキラル合成

In this review our own work on the development of chiral approaches to nitrogenous natural products based on a methodology involving conformational control in the transition states under nonchelation conditions has been presented. On 1, 2-asymmetric induction in the reaction of achiral reagents at the diastereotopic faces of a prochiral C=X (X=C, N, O etc.) group adjacent to an asymmetric carbon atom, the increased π-facial selectivity is brought about by conformational fixation of the single bond between the asymmetric center and the prochiral reaction center. Apart from cyclic chelation control, the useful ways to achieve this is to utilize the conformational restraints imposed by Cram-Felkin-Anh mode of nucleophilic addition, inside alkoxy effect, and allylic 1, 3-strain. Employing these nonchelation methodologies for controlling the stereochemistry of acyclic systems, we have succeeded in the enantiopure preparation of nitrogenous natural products including alkaloids, azasugars, and antibiotics.

Dissymmetric calix[4]arenes with C4- and C2-symmetry. Synthesis, x-ray structures, conformational fixation, and proton NMR spectroscopic studies

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDissymmetric calix[4]arenes with C4- and C2-symmetry. Synthesis, x-ray structures, conformational fixation, and proton NMR spectroscopic studiesGiovanni D. Andreetti, Volker Boehmer, J. Graham Jordon, Moniralsadat Tabatabai, Franco Ugozzoli, Walter Vogt, and Artur WolffCite this: J. Org. Chem. 1993, 58, 15, 4023–4032Publication Date (Print):July 1, 1993Publication History Published online1 May 2002Published inissue 1 July 1993https://doi.org/10.1021/jo00067a040RIGHTS & PERMISSIONSArticle Views1051Altmetric-Citations57LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (1 MB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts

Chiral helical Lewis acids for asymmetric Diels-Alder catalysts

A new type of chiral helical titanium reagent has been prepared from titanium tetraiopropoxide and a chiral ligand derived from optically pure binaphthol. These reagents have been successfully utilized as an efficient chiral template for the sufficient conformational fixation of α,β-unsaturated aldehydes, thereby allowing efficient enantioface recognition of the substrates for achievement of uniformly high symmetric induction in asymmetric Diels-Alder reaction with dienes, regardless of reaction temperature

Separation of Labile Terpenoids by Low Temperature HPLC

Abstract Semipreparative low temperature HPLC was used to isolate two sesquiterpene hydrocarbons, i. e. anastreptene and β-barbatene, that could not be separated at ambient temperature. A linear relationship was observed between the logarithm of capacity factor and the reciprocal of column temperature. This was consistent with previous reports (4, 5, 8). It could be demonstrated that differences in enthalpy and entropy may cause a temperature-dependent resolution for both compounds. Low temperature H-NMR revealed that separation was not due to a fixation of conformation.

In grosse Ringe eingebundene Cope-Systeme

The unsymmetrically double clamped Cope system 2 ( meso) unexpectedly formed from 12a and ethane dithiol, undergoes rearrangement despite the conformational fixation by the bridges. The constitution of 2 ( meso) is proven by an X-ray analysis. The stereochemistry of the rearrangements of 2 and 3 differs from that of the unbridged Cope systems 9, the Cope rearrangement of which was also studied.

A High-resolution 13C NMR Study of Some Ethylene Oxide Oligomers, Cryptands and Crown Ethers Complexed with a Variety of Metal Ions in the Solid State. Conformational Change of Ligand Molecules as Viewed from the Conformation-dependent Displacements of 13C Chemical Shifts

Abstract We recorded high-resolution solid-state 13C NMR spectra of ethylene oxide oligomers, cryptands, and crown ethers complexed with metal ions, determined by cross polarization-magic angle spinning (CP-MAS) NMR method. It is found that peak-intensities of these complexes are significantly enhanced by the presence of metal ions which act toward conformational fixation of flexible ligand molecules. The 13C chemical shifts of ethylene oxide oligomers complexed with HgCl2 or CdCl2 as open-chain analogues of crown ethers were successfully related with a pair of torsion angles of nearby single bonds. 13C Chemical shifts of cyclic ionophores were displaced (up to 6 ppm) together with conformational changes of ligand molecules. In addition, the 13C chemical shifts of the carbons neighbored with nitrogen atoms of cryptands [2.2.2] and [2.2.1] were well related with a pair of torsion angles of neaby bonds. Further, we found that several kinds of metal complexes with cis-syn-cis and cis-anti-cis isomers of dicyclohexano-18-crown-6 gave rise to substantially different spectral profiles, resulting in the occurrence of significant conformational changes of these ligand molecules as a result of complex formation.

Cross-linking study on skeletal muscle actin: interaction of suberimidate-treated actin with deoxyribonuclease I.

We have recently reported that actin modified with dimethyl suberimidate takes a filamentous form even under depolymerizing conditions, and this phenomenon is accounted for by the conformational fixation caused by the introduction of an intramolecular cross-link (Ohara, O., Takahashi, S., Ooi, T., & Fujiyoshi, Y. (1982) J. Biochem. 91, 1999-2012). The suberimidate-treated actin (SA) is not immediately depolymerized by deoxyribonuclease I (DNase I) but is depolymerized after incubation for one day, i.e., depolymerization is much slower than that for intact F-actin. The results on circular dichroic spectra of a mixture of SA and DNase I suggest that DNase I flips the conformation of SA into a G-actin-like state from the F-actin-like one when a tight SA-DNase I complex is formed. The suberimidate cross-link introduced in an SA molecule does not completely prevent the conformational change from the F-state to the G-state but stabilizes the actin conformation very greatly in the F-state.

Fixation of skeletal muscle actin in F-state by chemical cross-linking with bis-imidoesters

Actin monomer in rabbit skeletal muscle F-actin was intramolecularly cross-linked with bis-imidoesters. The modified protein possesses the properties of actin in a fibrous form even in the media of low salt concentrations which are favorable for the depolymerized form, G-actin. The result is interpreted as the fixation of the actin conformation in F-state.

N‐Terminal Cyclization of Peptides withN,N′‐Carbonyldiimidazole orN,N′‐Thiocarbonyldiimidazole

Partial conformational fixation of peptides by extremely mild N-terminal cyclization facilitates studies of structure-activity relations in peptide hormones and identification of the first two amino acids in a sequence.

A study of stepwise conformational changes in poly(beta-benzyl-L-aspartate) with the helix-coil transition by means of proton and carbon-13 NMR.

AbstractThe helix–coil transition for poly(β‐benzyl‐L‐aspartate) [poly(Asp[OBzl])] in solvent mixtures of trifluoroacetic acid/deuterated chloroform (F3AcOH/CDCl3) was studied by means of proton and carbon‐13 nmr. Conformational fixation of the side chain occurs before the coil–helix transition of the backbone, when neighboring phenyl rings face each other. Another type of conformational fixation occurs in the side chain after the coil–helix transition of the backbone. These conformational changes of the side chain are due to the changes of the strength of the interaction between the side‐chain ester group and the F3AcOH molecule. In the absence of F3AcOH (coil‐forming solvent), the polymer has a rather rigid structure in which the side chain may wrap around the backbone. These conformational changes of the polymer are closely related to the changes of the interaction between the polymer and F3AcOH molecules.

Etudes cinétiques et conformationnelles par résonance magnétique nucléaire—XV : Fixation conformationnelle et rigidité de systèmes bicycliques du type [2.2.n

The method of “ conformational fixation” 2,5 using the geometrical and energetical properties inherent to the diurethane fragment N(COOMe)N(COOMe) to lock conformations and to slow down conformational equilibria, has been applied to the study of bicyclic systems of type [2.2.n] (n = 1–4). The introduction of the diurethane fragment into these systems permits the observation of a twisted conformation of the bicyclic molecules and of an equilibrium B ⇌ C between such conformations. Approximate values of the barriers hindering the interconversion B ⇌ C have been measured; they may be considered as an indirect estimate of the flexibility of the different bicyclic systems. A “ flexibility index” may be defined. Attributing a value of 1 to an acyclic reference molecule (V), leads to the following indices: ⩽0·6; 0·75 (0·85); 0·85; 0·95 respectively for systems of the type bicyclo[2.2.1]heptane, bicyclo[2.2.2]octane, bicyclo[3.2.2]nonane, bicyclo[4.2.2]decane. Some nitrogen inversion barriers have also been measured for the corresponding N.N′-dimethyl-diaza-bicyclic systems. The potential usefulness of the “ conformational fixation” method is briefly discussed and the general concept involved is delineated.

NMR Studies of the rate processes and conformations—X: Conformational rate processes in di-, tetra- and hexa-hydropyridazine systems

The NMR spectra of various pyridazine derivatives containing the N(COOR)N(COOR) fragment have been studied. These spectra are temperature dependent. Free enthalpies of activation have been calculated from the observed spectral changes. These changes have been related to conformational changes in the molecules studied. Hindered rotation about the NCOOR bonds is present in all compounds studied. A ring inversion process is observed in the compounds of the tetra- and hexa-hydro-pyridazine types. A “ ring twisting” process is found in a dihydropyridazine derivative. The origin of the potential barriers for these processes is discussed. The geometrical and energetical analogies observed for a number of rate processes arise from the presence of the N(COOR)N(COOR) fragment in the systems studied. It is suggested that this fragment introduces a “conformational fixation” and may serve as a useful probe into molecular dissymetry and conformational changes.