Regio‐ and stereo‐selectivity in the silylation of 2,6‐diethyl‐3,4,7,8‐tetramethyl‐1,5‐dihydro‐s‐indacene

Disilylation of 2,6‐diethyl‐3,4,7,8‐tetramethyl‐1,5‐dihydro‐s‐indacene is regioselective and stereoselective. The stereoselectivity was modified by changing the experimental conditions, allowing an understanding of the reaction mechanism. The structure of the ‘meso’ diastereoisomer was established by X‐ray diffraction. Copyright © 2006 John Wiley & Sons, Ltd.     

Fate of the Oxygen Atoms in the Diol‐Dehydratase‐Catalyzed Dehydration of meso‐Butane‐2,3‐diol

¹⁸O‐Substituted propane‐1,2‐diols and meso‐butane‐1,2‐diols were synthesized and fed to growing cells of Lactobacillus brevis. Propan‐1‐ol and butan‐2‐ol, prepared from such diols through diol‐dehydratase‐catalyzed dehydration followed by intracellular reduction, were analyzed for their ¹⁸O‐content. For each propane‐1,2‐diol enantiomer, partial retention or complete loss of the isotope appeared to be related to the mode of substrate binding. Specific retention of the O‐atom linked to the (R)‐configured C‐atom of meso‐butane‐1,2‐diol indicates that the diol dehydratase handles this substrate like (R)‐propane‐1,2‐diol.     

A study of the planarity of the pyrrolone fragment in 2‐isopropyl‐2,3‐dihydro‐1H‐isoindol‐1‐one

Orthophthalaldehyde (o‐phthalaldehyde, OPA) is an aromatic dialdehyde bearing two electron‐withdrawing carbonyl groups. The reactions of OPA with primary amines are broadly applied for the synthesis of important heterocyclic compounds with biological relevance. A number of such reactions have been investigated recently and several structures of condensation products have been reported, however, the complex reaction mechanism is still not fully understood and comprises concurrent as well as consecutive reactions. The reaction products depend on the primary amine which reacts with OPA, the reaction environment (solvent) and the proportion of the reactants. The title molecule, C₁₁H₁₃NO, the product of the reaction of OPA with isopropylamine, contains a five‐membered pyrrole C₄N ring with a carbonyl substituent, which forms part of the isoindolinone unit. Though this pyrrole ring contains one C atom in the sp³‐hybridized state, it is fairly planar. The title molecule has been compared with similar structures retrieved from the Cambridge Structural Database in order to study this phenomenon. The planarity of this fragment has been explained by the presence of partially delocalized C—C, C—N and C—O bonds, and by an inner angle in the planar pentagonal ring (∼108°), which is close to the ideal tetrahedral value for the sp³‐hybridized state of the constituent C atom. Due to this propitious angle, this C atom can be present in states intermediate between sp³‐ and sp²‐hybridized in different structures, while still maintaining the planarity of the ring. There are only weak intermolecular C—H…O hydrogen bonds and C—H…π‐electron ring interactions in the structure. In particular, it is the pyrrole ring which is involved in these interactions.     

CrB‐Type Phases in the Tb‐Zr‐Al‐Si System

The crystal structures of Tb(Al_0.15Si_0.85), (Tb_0.70Zr_0.30)(Al_0.17Si_0.83) and Zr(Al_0.22Si_0.78) have been refined from single‐crystal X‐ray diffraction data. The three compounds crystallize with CrB‐type structures (Pearson symbol oS8, space group Cmcm): Tb(Al_0.15Si_0.85): a = 4.2715(5), b = 10.5595(15), c = 3.8393(5) Å; (Tb_0.70Zr_0.30)(Al_0.17Si_0.83): a = 4.163(2), b = 10.423(5), c = 3.8543(18) Å; Zr(Al_0.22Si_0.78): a = 3.7824(6), b = 10.0164(16), c = 3.7795(5) Å. The existence of a significant CrB‐type solid solution in the quaternary system Tb‐Zr‐Al‐Si, based on the ternary compound Tb(Al_0.15Si_0.85) and extending toward the solid solution based on the binary compound ZrSi in the Zr‐Al‐Si system, cannot be excluded.     

Solid‐state conformation of the 1,3,2‐oxazaphospholane ring in 2‐dialkylamino‐3,4‐dimethyl‐5‐phenyl‐1,3,2‐oxazaphospholane sulfides

Dialkylamino‐3,4‐dimethyl‐5‐phenyl‐1,3,2‐oxazaphospholane sulfides (where the alkyl is an isopropyl, ethyl or methyl group) was obtained by sulfurization of the respective phospholanes. The structures of these compounds were determined by X‐ray crystal structure analysis. Five‐membered rings exist in the envelope conformation in the crystalline state. The planar part of the 1,3,2‐oxazaphospholane rings undergoes twisting with the enlargement of a substituent. The environment of the P atom has the geometry of a distorted tetrahedron. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:146–150, 2001     

Probing the Conformational Changes in the Enzymatic Hydrolysis of 2‐Acetamido‐2‐deoxy‐β‐D‐glucopyranosides

The isoquinuclidines 7 and 8 were synthesised and tested as inhibitors of hexosaminidases from jack beans and from bovine kidney. These isoquinuclidines mimick the ^1,4B‐conformer of a N‐acetyl‐glucosamine‐derived β‐d‐ glucopyranoside; they are competitive inhibitors with K_i values from 0.014 to 0.30 μM . The strong inhibition of these enzymes agrees with the hypothesis that the enzymatic hydrolysis of 2‐acetamido‐2‐deoxy‐β‐d‐ glucopyranosides proceeds via a boat‐like conformer with a pseudo‐axial scissile glycosidic bond and a pseudo‐axial acetamido substituent optimally oriented to effect an intramolecular substitution of the aglycon.     

Similarities and differences in the structures of 5‐bromo‐6‐hydroxy‐7,8‐dimethylchroman‐2‐one and 6‐hydroxy‐7,8‐dimethyl‐5‐nitrochroman‐2‐one

The title compounds, C₁₁H₁₁BrO₃, (I), and C₁₁H₁₁NO₅, (II), respectively, are derivatives of 6‐hydroxy‐5,7,8‐trimethylchroman‐2‐one substituted at the 5‐position by a Br atom in (I) and by a nitro group in (II). The pyranone rings in both molecules adopt half‐chair conformations, and intramolecular O—H...Br [in (I)] and O—H...O_nitro [in (II)] hydrogen bonds affect the dispositions of the hydroxy groups. Classical intermolecular O—H...O hydrogen bonds are found in both molecules but play quite dissimilar roles in the crystal structures. In (I), O—H...O hydrogen bonds form zigzag C(9) chains of molecules along the a axis. Because of the tetragonal symmetry, similar chains also form along b. In (II), however, similar contacts involving an O atom of the nitro group form inversion dimers and generate R₂²(12) rings. These also result in a close intermolecular O...O contact of 2.686 (4) Å. For (I), four additional C—H...O hydrogen bonds combine with π–π stacking interactions between the benzene rings to build an extensive three‐dimensional network with molecules stacked along the c axis. The packing in (II) is much simpler and centres on the inversion dimers formed through O—H...O contacts. These dimers are stacked through additional C—H...O hydrogen bonds, and further weak C—H...O interactions generate a three‐dimensional network of dimer stacks.     

The Role of Weak Interactions in the Mechano‐induced Single‐Crystal‐to‐Single‐Crystal Phase Transition of 8‐Hydroxyquinoline‐Based Co‐crystals

Mechano‐induced single‐crystal‐to‐single‐crystal (SCSC) phase transitions in crystalline materials that change their properties have received more and more attention. However, there are still too few examples to study molecular‐level mechanisms in the mechano‐induced SCSC phase transitions, making the systematic and in‐depth understanding very difficult. We report that bis‐(8‐hydroxyquinolinato) palladium(II)‐tetracyanoquinodimethane (PdQ₂‐TCNQ) and bis‐(8‐hydroxyquinolinato) copper(II)‐tetracyanoquinodimethane (CuQ₂‐TCNQ) show very different mechano‐response behaviors during the SCSC phase transition. Phase transition in CuQ₂‐TCNQ can be triggered by pricking on the crystal surface, while in PdQ₂‐TCNQ it can only be induced by applying pressure uniformly over the whole crystal face. The crystallography data and Hirshfeld surface analysis indicate that the weak intra‐layer C?H???O, C?H???N hydrogen bonds and inter‐layer stacking interactions determine the feasibility of the SCSC phase transition by mechanical stimuli. Weaker intra‐layer interactions and looser inter‐layer stacking make the SCSC phase transition occur much more easily in the CuQ₂‐TCNQ.     

Effect of the Side‐Chain‐Distribution Density on the Single‐Conjugated‐Polymer‐Chain Conformation

The spatial arrangement of the side chains of conjugated polymer backbones has critical effects on the morphology and electronic and photophysical properties of the corresponding bulk films. The effect of the side‐chain‐distribution density on the conformation at the isolated single‐polymer‐chain level was investigated with regiorandom (rra‐) poly(3‐hexylthiophene) (P3HT) and poly(3‐hexyl‐2,5‐thienylene vinylene) (P3HTV). Although pure P3HTV films are known to have low fluorescence quantum efficiencies, we observed a considerable increase in fluorescence intensity by dispersing P3HTV in poly(methyl methacrylate) (PMMA), which enabled a single‐molecule spectroscopy investigation. With single‐molecule fluorescence excitation polarization spectroscopy, we found that rra‐P3HTV single molecules form highly ordered conformations. In contrast, rra‐P3HT single molecules, display a wide variety of different conformations from isotropic to highly ordered, were observed. The experimental results are supported by extensive molecular dynamics simulations, which reveal that the reduced side‐chain‐distribution density, that is, the spaced‐out side‐chain substitution pattern, in rra‐P3HTV favors more ordered conformations compared to rra‐P3HT. Our results demonstrate that the distribution of side chains strongly affects the polymer‐chain conformation, even at the single‐molecule level, an aspect that has important implications when interpreting the macroscopic interchain packing structure exhibited by bulk polymer films.     

Novel Delta‐Opioid‐Receptor‐Selective Ligands in the 14‐Alkoxy‐Substituted Indolo‐ and Benzofuromorphinan Series

Several new indolo‐ and benzofuromorphinans substituted at the positions 5 and 14 were prepared and tested in vitro by means of opioid‐receptor binding and functional ([³⁵S]GTPγS binding) assays. All compounds 1 – 11 displayed high affinity for δ opioid‐binding sites (Table 1). Compound 4 proved to be an agonist, and all other compounds were antagonists. The presence of a Me group at position 5 induced no change in δ affinity (see 1 vs. 3 ), but decreased the μ and κ affinities. An EtO group at position 14 conferred a very high affinity and also high selectivity to δ opioid receptors (see 2 and 10 ). Chain elongation of the 14‐alkoxy group resulted in compounds with reduced δ affinity and selectivity (see 4 and 11 and also 5 – 9 ). The results of the present study indicate that the 5‐ and 14‐positions of indolo‐ and benzofuromorphinans represent critical sites that could be a trigger to develop new compounds with increased δ affinity and/or selectivity.     

A new direction in the alkylation of 5‐acetyl‐2‐amino‐6‐methyl‐4‐phenyl‐4H‐pyran‐3‐carbonitrile with active methylene reagents

In this paper, we report a new synthesis route to 4H‐pyran derivatives and a plausible reaction mechanism. The interaction of 5‐acetyl‐2‐amino‐6‐methyl‐4‐phenyl‐4H‐pyran‐3‐carbonitrile with different active methylene reagents gives rise to the cleavage and subsequent recyclization of the pyran ring to afford the corresponding 4H‐pyran derivatives.     

Hydrogen bonding in meso‐4,5‐diphenyl‐3,6‐diaza­octane‐1,8‐diol: the formation of one‐dimensional linear chains of edge‐fused rings

The molecule of the title compound, C₁₈H₂₄N₂O₂, resides on a crystallographic inversion centre. The mol­ecule adopts a transoid conformation with respect to the central C—C single bond and is in the meso form. A polarimetric study of the compound did not show any optical activity, indicating that the compound is a racemic mixture entirely consistent with the centrosymmetric space group. In the mol­ecule, there is one intra­molecular N—H⋯O inter­action, resulting in the formation of a five‐membered ring. In the crystal structure, inter­molecular O—H⋯N and C—H⋯O inter­actions are also observed. These inter­actions form an R₂²(9) ring and one‐dimensional linear chains of edge‐fused rings running parallel to the [010] direction, which stabilize the crystal packing.     

Asymmetric cyclopolymerization of N‐tert‐butyl‐N‐allylacrylamide in the presence of β‐cyclodextrin

The radical polymerization of N‐tert‐butyl‐N‐allylacrylamide (t‐BAA) was carried out in a dimethyl sulfoxide/H₂O mixture in the presence of β‐cyclodextrin (β‐CD). The polymerization proceeded with the complete cyclization of the t‐BAA unit and yielded optically active poly(t‐BAA). The IR spectrum of the obtained polymer showed that the cyclic structure in the polymer was a five‐membered ring. The optical activity of poly(t‐BAA) increased with an increasing molar ratio of β‐CD to the t‐BAA monomer. The interaction of β‐CD with t‐BAA was confirmed by ¹H NMR and ¹³C NMR analyses of the polymerization system. It is suggested that interaction of the t‐BAA monomer with the hydrophobic cavity of β‐CD plays an important role in the asymmetric cyclopolymerization of t‐BAA. The radical copolymerization of t‐BAA with styrene (St), methyl methacrylate, ethyl methacrylate, or benzyl methacrylate (BMA) also produced optically active copolymers with a cyclic structure from the t‐BAA unit. St and BMA carrying a phenyl group were predicted to compete with t‐BAA for interaction with β‐CD in the copolymerization system. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 2098–2105, 2000     

The 2‐Cyano‐2,2‐dimethylethanimine‐N‐oxymethyl Group for the 2′‐Hydroxyl Protection of Ribonucleosides in the Solid‐Phase Synthesis of RNA Sequences

The reaction of 2‐cyano‐2‐methyl propanal with 2′‐O‐aminooxymethylribonucleosides leads to stable and yet reversible 2′‐O‐(2‐cyano‐2,2‐dimethylethanimine‐N‐oxymethyl)ribonucleosides. Following N‐protection of the nucleobases, 5′‐dimethoxytritylation and 3′‐phosphitylation, the resulting 2′‐protected ribonucleoside phosphoramidite monomers are employed in the solid‐phase synthesis of three chimeric RNA sequences, each differing in their ratios of purine/pyrimidine. When the activation of phosphoramidite monomers is performed in the presence of 5‐benzylthio‐1H‐tetrazole, coupling efficiencies averaging 99 % are obtained within 180 s. Upon completion of the RNA‐chain assemblies, removal of the nucleobase and phosphate protecting groups and release of the sequences from the solid support are carried out under standard basic conditions, whereas the cleavage of 2′‐O‐(2‐cyano‐2,2‐dimethylethanimine‐N‐oxymethyl) protective groups is effected (without releasing RNA alkylating side‐products) by treatment with tetra‐n‐butylammonium fluoride (0.5 m) in dry DMSO over a period of 24–48 h at 55 °C. Characterization of the fully deprotected RNA sequences by polyacrylamide gel electrophoresis (PAGE), enzymatic hydrolysis, and matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry confirmed the identity and quality of these sequences. Thus, the use of 2′‐O‐aminooxymethylribonucleosides in the design of new 2′‐hydroxyl protecting groups is a powerful approach to the development of a straightforward, efficient, and cost‐effective method for the chemical synthesis of high‐quality RNA sequences in the framework of RNA interference applications.     

Application of the acetate of baylis‐hillman adducts in the synthesis of 3‐carbomethoxy‐2H‐thiochromenes

A new route to 2H‐thiochromenes using the tandem S_N2′ and S_NAr reaction of several Baylis‐Hillman acetates having an ortho‐substituent, such as a halogen or nitro group, with sodium sulfide in aqueous dimethyl sulfoxide has been described.     

Conformations of the Nine‐Membered Ring in the B‐Nor‐5,10‐secosteroids. X‐Ray and NMR Analysis

The conformations of (Z)‐ and (E)‐5‐oxo‐B‐nor‐5,10‐secocholest‐1(10)‐en‐3β‐yl acetates ( 2 and 3 , resp.) were examined by a combination of X‐ray crystallographic analysis and NMR spectroscopy, with emphasis on the geometry of the cyclononenone moiety. The ¹H‐ and ¹³C‐NMR spectra showed that the unsaturated nine‐membered ring of (E)‐isomer 3 in C₆D₆ and (D₆)acetone solution exists in a sole conformation of type B ₁ , which is similar to its solid‐state conformation. The (Z)‐isomer 2 in C₆D₆, CDCl₃, and (D₆)acetone solution, however, exists in two conformational forms of different families, with different orientation of the carbonyl group, the predominant form (85%) corresponding to the conformation of type A ₁ and the minor (15%) to the conformation A ₂ present also in the crystalline state. In this solid‐state conformations of the nine‐membered ring of both compounds, the 19‐Me and 5‐oxo groups are ‘β’‐oriented. The NMR analysis suggests that the nine‐membered ring of 4 has a conformation of type C ₁ in CDCl₃ solution.     

Solvent‐Enhanced Diastereo‐ and Regioselectivity in the PdII‐Catalyzed Synthesis of Six‐ and Eight‐Membered Heterocycles via cis‐Aminopalladation

The Pd^II‐catalyzed intramolecular oxidative cyclization of tosyl‐protected cis‐ and trans‐N‐allyl‐2‐aminocyclohexanecarboxamides was examined, and efficient syntheses of cyclohexane‐fused pyrimidin‐4‐ones and 1,5‐diazocin‐6‐ones were developed. In the course of the research, a marked solvent effect was observed on both the regio‐ and diastereoselectivity. Additionally, a novel Pd^II‐mediated domino oxidation, oxidative amination reaction was discovered. Our experimental and theoretical findings suggest that the reactions proceed via a cis‐aminopalladation mechanism.     

Temperature‐induced aggregation of the copolymers of N‐isopropylacrylamide and sodium 2‐acrylamido‐2‐methyl‐1‐propanesulphonate in aqueous solutions

A series of random copolymers of N‐isopropylacrylamide (NIPAM) and sodium 2‐acrylamido‐2‐methyl‐1‐propanesulphonate (AMPS) was synthesized by free‐radical copolymerization. The content of AMPS in the copolymers ranged from 1.1 to 9.6 mol %. The lower critical‐solution temperature (LCST) of copolymers in water increased strongly with an increasing content of AMPS. The influence of polymer concentration on the LCST of the copolymers was studied. For the copolymers with a higher AMPS content, the LCST decreased faster with an increasing concentration than for copolymers with a low content of AMPS. For a copolymer containing 1.1 mol % of AMPS the LCST dropped by about 3 °C when the concentration increased from 1 to 10 g/L, whereas for a copolymer containing 9.6 mol % of AMPS the LCST dropped by about 10 °C in the concentration range from 2 to 10 g/L. It was observed that the ionic strength of the aqueous polymer solution very strongly influences the LCST. This effect was most visible for the copolymer with the highest content of AMPS (9.6 mol %) for which an increase in the ionic strength from 0.2 to 2.0 resulted in a decrease in the LCST by about 27 °C (from 55 to 28 °C), whereas for the copolymer containing 1.1 mol % of AMPS the LCST decreased only by about 6 °C (from 37 to 31 °C) when the ionic strength increased from 0.005 to 0.3. The reactivity ratios for the AMPS and NIPAM monomer pairs were determined using different methods. The values of r_AMPS and r_NIPAM obtained were 11.0–11.6 and 2.1–2.4, respectively. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 2784–2792, 2001     

ECEC and ECE‐Type Mechanisms in Electrochemical Oxidation of 4‐Substituted Catechols in the Presence of 4‐Hydroxy‐6‐methyl‐2‐pyrone

Electrochemical oxidation of 3,4‐dihydroxybenzoic acid ( 1 ) and 4‐tert‐butylcatechol ( 5 ) in the presence of 4‐hydroxy‐6‐methyl‐2‐pyrone ( 2 ) as nucleophile in aqueous solution has been studied using cyclic voltammetry and controlled‐potential coulometry. The results indicate that 1 via Michael reaction under electro‐decarboxylation reaction converts to heterocyclic compound 4 , and the quinone derived from 4‐tert‐butylcatechol ( 5 ) participates in Michael reaction with 2 and through an ECE mechanism converts to the corresponding o‐quinone ( 6a ). The electrochemical synthesis of 4 and 6a has been successfully performed in an undivided cell.