Conformationally Locked Research Articles

Enantio- and Diastereomerically Pure Titanocenes by Dynamic Conformational Locking.

The synthesis of enantiomerically pure titanocenes is limited to cases with enantiomerically pure substituents at the cyclopentadienyl ligands and to ansa-titanocenes. For the latter complexes, the use of achiral ligands requires a resolution of enantiomers and frequently also a separation of the diastereoisomers obtained after metalation. Here, we introduce a new synthetic method that relies on the use of enantiomerically pure camphorsulfonate (CSA) ligands as control elements for the absolute and relative configuration of titanocene complexes. Starting from the conformationally flexible (RC5 H4 )2 TiCl2 , the desired conformationally locked and hence enantio- and diastereomerically pure complexes (RC5 H4 )2 Ti(CSA)2 are obtained in just two steps. According to X-ray crystallography the (RC5 H4 )2 Ti fragment is essentially C2 -symmetric and nuclear magnetic resonance displays overall C2 -symmetry. We applied density functional theory methods to unravel the dynamics of the complexes and the mechanisms and selectivities of their formation.

Synthesis and Optical Properties of the Conformationally Locked Diarylmethene Derivative of the GFP Chromophore

Synthesis and Optical Properties of the Conformationally Locked Diarylmethene Derivative of the GFP Chromophore

Conformationally locked cis-1,2-diaminocyclohexane-based chiral ligands for asymmetric catalysis

An efficient synthesis for a new conformationally locked chiral cis-1,2-diaminocyclohexane scaffold has been developed. The conformational lock allows for convenient symmetrical derivatization of the amino groups through the reductive amination strategy. A series of optically pure chiral ligands based on the cis-DACH scaffold has been generated to demonstrate a proof-of-concept for these ligands as chiral catalysts in the asymmetric Henry reaction. Excellent yields with moderate enantioselectivity were demonstrated at room temperature, with an increase in enantioselectivity at lower temperatures, showing the potential of this new type of cis-DACH ligand.

Lability of Stationary and Time-Resolved Optical Properties of the Conformationally Locked CFP Chromophore Derivative

Lability of Stationary and Time-Resolved Optical Properties of the Conformationally Locked CFP Chromophore Derivative

Synthesis and Optical Properties of the Conformationally Locked Indole and Indoline Derivatives of the GFP Chromophore

We report novel conformationally locked GFP chromophore amino-derivatives containing indole and indoline moieties. Optical properties of these compounds were studied. The introduction of the indoline group produces a shift in the absorption and emission maxima to the long-wavelength region and stabilizes the quantum yield of fluorescence. The introduce of the indole group leads to a hypsochromic shift and a noticeable decrease of fluorescence intensity.

Effect of Remote Polyene Bridge Methyl Substituent on Physical Properties of Dipolar Chromophores with Conformationally and Configurationally Locked Polyene Bridge

Effect of Remote Polyene Bridge Methyl Substituent on Physical Properties of Dipolar Chromophores with Conformationally and Configurationally Locked Polyene Bridge

Bicyclo[3.2.0]heptane as a Core Structure for Conformational Locking of 1,3-Bis-Pharmacophores, Exemplified by GABA.

The synthesis and X-ray crystal structures of syn and anti 4-N-Boc-aminobicyclo[3.2.0]heptane-1-carboxylic acids are described. The placement of the N-Boc-amino groups in the two stereoisomers in either pseudo-equatorial or pseudo-axial positions renders the molecules conformationally locked, with N-Boc-protected γ-aminobutyric acid (GABA) embedded within the bicyclic core. Despite the different conformations of the urethane and distinct crystal packing, the bicyclic core units of the two stereoisomers adopt virtually identical structures. They correspond to in silico models of the parent bicyclic core and a systematic array of disubstituted derivatives. The study documents an intrinsic property of the bicyclo[3.2.0]heptane core to favor adoption of a boat-like conformation, which is largely unaffected by various substitution patterns. The structural concepts are useful in the design of molecules with spatial and directional fixation of pharmacophoric groups.

Bioinspired Fluorescent Dyes Based on a Conformationally Locked Chromophore of the Fluorescent Protein Kaede

AbstractA novel class of fluorescent dyes based on the conformationally locked heterocyclic core of the chromophore of the fluorescent protein Kaede was discovered. Introduction of a single conformational lock at the benzylidene fragment of the Kaede chromophore resulted in an increase in the fluorescence quantum yield (FQY) by one order of magnitude and a redshift of ca. 60 nm in the emission spectrum. Imposing the second lock at the ethylene fragment of the Kaede chromophore provided a further increase in the FQY. Locked analogues demonstrated bright and redshifted emission in a broad range of solvents, which makes them good candidates for a wide spectrum of fluorescent‐labeling applications.

Direct thiophenylation accompanying orthoester-cleavage of 1,2,4-O-orthoacetyl-3,6-O-(o-xylylene)glucopyranose

The 3,6-O-(o-xylylene) bridge locks the conformation of glucopyranose to an axial-rich form. Although the conformational lock induces complete β-selectivity in a glycosylation reaction, the leaving group of the glycosyl donor is limited to fluorine. On the other hand, the bridge confers the furanose-preferred property to glucose, which makes synthesis of corresponding pyranosyl derivatives that equip various leaving groups difficult. This problem was solved through direct phenylthio glucosidation of 3,6-O-(o-xylylene)-1,2,4-O-orthoacetylglucose accompanying cleavage of the orthoester moiety. This paper describes the process of establishing direct thiophenylation. This process reduced the synthetic steps for the known glucopyranosyl fluoride and will expand application of conformationally locked glycosyl donors.

ChemInform Abstract: Conformationally Locked Nucleoside Analogues Based on the Bridgehead Substituted 7‐Oxonorbornane and Their Antiviral Properties.

AbstractA series of novel conformationally‐constrained nucleoside analogues with an aromatic ring employed as the locking bridge is designed, synthesized and tested for antiviral properties.

Cover Picture: Crystal Structures of Conformationally Locked Cyclitols: An Analysis of Hydrogen‐Bonded Architectures and their Implications in Crystal Engineering (Eur. J. Org. Chem. 3/2007)

AbstractThe cover picture shows schematically, the manner in which a conformationally locked polycyclitol can be thought of as a LEGO® brick in the supramolecular world. This analogy manifests during the self‐assembling process by involvement of intermolecular H‐bond donors and acceptors engendered in preordained positions through the rigid trans‐decalin framework and intramolecular O–H···O hydrogen bonding between the 1,3‐diaxial OH groups. Details are discussed in the article by G. Mehta et al. on p. 423 ff.

Synthesis of Conformationally Locked Carbocyclic Nucleosides Built on a Thiabicyclo[3.1.0]hexane System as a Pseudosugar Surrogate

AbstractThe synthesis of prototype models of purine and pyrimidine carbanucleosides built on a 6‐thiabicyclo[3.1.0]hexane system as pseudosugar moiety has been investigated. These pyrimidine carbanucleosides proved to be very stable compounds, in contrast to the parent epoxy analogs, which experienced epoxide ring‐opening due to intramolecular enol base attack. In addition, as the synthesis of a thiirane moiety fused to a five‐membered ring is not a trivial synthetic task, validation and optimization of the existing methods for episulfide preparation were required to access the committed synthetic precursor of the title compounds: (±)‐(1RS,2RS,5SR)‐6‐thiabicyclo[3.1.0]hexan‐2‐ol, compound 28. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Cover Picture: A New Glucose: Towards Conformationally Locked Hexoses through Annulation (Eur. J. Org. Chem. 11/2005)

AbstractThe cover picture shows the concept of carbocyclic annulation (trans‐ring fusion) to lock hexoses, such as β‐glucose, in their unnatural axial‐rich conformation, while retaining their natural configuration. The bipolarofacial nature of these novel cyclohexane ring annulated sugar entities is reflected in their channel‐like supramolecular assembly in the solid state, consisting of a hydrophilic interior and a hydrophobic exterior. Details are discussed in the article by G. Mehta and S. S. Ramesh on p. 2225 ff.

A New Glucose: Towards Conformationally Locked Hexoses through Annulation

AbstractA new family of surface‐modified carbohydrates with locked, axial‐rich conformations and bipolarofacial architectures has been developed with the aid of carbocyclic ring annulation. These novel trans‐decalin‐based carbohydrates have been synthesized, from simple aromatic precursors such as tetralin, through the ozonolysis of an appropriately protected allylic alcohol, followed by a cascade of intramolecular acetalizations to generate the sugar pyran moiety. The stereoselective synthesis of (racemic) cyclohexane‐annulated β‐glucopyranoside and α‐glucofuranoside from a common annulated trans‐cyclohexadiene diol (trans‐CHD) precursor underscores the versatility of our approach. The efficacy of the annulation stratagem in generating carbohydrate diversity has been demonstrated through the synthesis of two regioisomeric annulated gulose derivatives, which differ only in the site of ring annulation on the sugar moiety. The mapping of the MLP surface and solid‐state architecture of the new sugar shows that cycloalkane annulation results in surface modification and fine‐tuning of sugar hydrophilicity. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

New Conformationally Locked Bicyclic N,O‐Nucleoside Analogues of Antiviral Drugs.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of a Novel Conformationally Locked Carbocyclic Nucleoside Ring System.

A fast and efficient synthetic route to novel Northern locked carbocyclic nucleosides (as precursors of carbocyclic locked nucleic acids or cLNAs) is described. The target nucleoside with a oxabicyclo[2.2.1]heptane ring system was prepared from a simple starting material, diethyl malonate. Ring closure by intramolecular O-alkylation provided the target ring system as the major isomer over the [3.2.0] oxetane system. The adenine moiety was introduced through a reactive triflate after inversion of the stereochemistry of the corresponding alcohol by oxidation and reduction.

ChemInform Abstract: Conformationally Locked Carbocyclic Nucleosides Built on a Bicyclo(3.1. 0)hexane Template with a Fixed Southern Conformation. Synthesis and Antiviral Activity.

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.

ChemInform Abstract: STEREOELECTRONIC CONTROL OF THE HYDROLYSIS OF A CONFORMATIONALLY LOCKED ACETAL

Chemischer InformationsdienstVolume 15, Issue 7 Preparative Organic Chemistry ChemInform Abstract: STEREOELECTRONIC CONTROL OF THE HYDROLYSIS OF A CONFORMATIONALLY LOCKED ACETAL A. J. KIRBY, A. J. KIRBYSearch for more papers by this authorR. J. MARTIN, R. J. MARTINSearch for more papers by this author A. J. KIRBY, A. J. KIRBYSearch for more papers by this authorR. J. MARTIN, R. J. MARTINSearch for more papers by this author First published: February 14, 1984 https://doi.org/10.1002/chin.198407082Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume15, Issue7February 14, 1984 RelatedInformation

ChemInform Abstract: STEREOELECTRONIC EFFECTS AT OXYGEN. A VERY LARGE EFFECT ON THE HYDROLYSIS OF A CONFORMATIONALLY LOCKED ACETAL: IMPLICATIONS FOR β‐GLYCOSIDASE MECHANISMS

Chemischer InformationsdienstVolume 15, Issue 7 Preparative Organic Chemistry ChemInform Abstract: STEREOELECTRONIC EFFECTS AT OXYGEN. A VERY LARGE EFFECT ON THE HYDROLYSIS OF A CONFORMATIONALLY LOCKED ACETAL: IMPLICATIONS FOR β-GLYCOSIDASE MECHANISMS A. J. BRIGGS, A. J. BRIGGSSearch for more papers by this authorC. M. EVANS, C. M. EVANSSearch for more papers by this authorR. GLENN, R. GLENNSearch for more papers by this authorA. J. KIRBY, A. J. KIRBYSearch for more papers by this author A. J. BRIGGS, A. J. BRIGGSSearch for more papers by this authorC. M. EVANS, C. M. EVANSSearch for more papers by this authorR. GLENN, R. GLENNSearch for more papers by this authorA. J. KIRBY, A. J. KIRBYSearch for more papers by this author First published: February 14, 1984 https://doi.org/10.1002/chin.198407084Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume15, Issue7February 14, 1984 RelatedInformation