Negative Cooperativity in the Molecular Recognition of Excitatory Amino-Acid Derivatives by Synthetic Allosteric 1,1′-Binaphthalene Receptors

The optically active allosteric receptors (−)-(R,R)- 3 and (+)-(R,R)- 4 were synthesized for the molecular recognition of the N-(benzyloxy)carbonyl (N-Cbz)-protected excitatory amino acids aspartic acid (Asp, 1 ) and glutamic acid (Glu, 2 ). These macrocyclic structures consist of two 1,1′-binaphthalene moieties connected by two but-2-yne-1,4-diyl (for (−)-(R,R)- 3 ) or p-xylylene (for (+)-(R,R)- 4 ) bridges between the O-atoms in the minor grooves. Each 1,1′-binaphthalene moiety contains two 2-acetamidopyridin-6-yl (CONH(py)) H-bonding sites in the major groove to bind excitatory amino-acid derivatives via two COOH█bk█⋅⋅⋅█ek█CONH(py) H-bonding arrays and additional secondary electrostatic interactions. The formation of stable complexes with 1 : 2 host-guest stoichiometry was proven by the evaluation of fluorescence binding titrations using a multiple-wavelength nonlinear least-squares curve-fitting procedure, Job plot analysis, and solubilization experiments. Complexation of the first excitatory amino-acid guest at binding site 1 reduces the affinity for the second guest at binding site 2. As measures for the negative cooperativity between the two sites, the ratios of the association constants for the first and second binding events, {K_a(1 : 1)/K_a(1 : 2)}_corr. (corrected for the statistical preference of the 1 : 1 complex formation), were found to adopt values between 1.4 and 2.4, and the Hill coefficients n_H varied between 0.49 and 0.59.     

Functionalized 3,3′,5,5′‐Tetraaryl‐1,1′‐Biphenyls: Novel Platforms for Molecular Receptors

This paper describes the development of novel aromatic platforms for supramolecular construction. By the Suzuki cross‐coupling protocol, a variety of functionalized m‐terphenyl derivatives were prepared (Schemes 1–4). Macrolactamization of bis(ammonium salt) (S,S)‐ 6 with bis(acyl halide) 7 afforded the macrocyclic receptor (S,S)‐ 2 (Scheme 1), which was shown by ¹H‐NMR titration studies to form ‘nesting' complexes of moderate stability (K_a between 130 and 290 M ^?1, 300 K) with octyl glucosides 13 – 15 (Fig. 2) in the noncompetitive solvent CDCl₃. Suzuki cross‐coupling starting from 3,3′,5,5′‐tetrabromo‐1,1′‐biphenyl provided access to a novel series of extended aromatic platforms (Scheme 5) for cleft‐type (Fig. 1) and macrotricyclic receptors such as (S,S,S,S)‐ 1 . Although mass‐spectral evidence for the formation of (S,S,S,S)‐ 1 by macrolactamization between the two functionalized 3,3′,5,5′‐tetraaryl‐1,1′‐biphenyl derivatives (S,S)‐ 33 and 36 was obtained, the ¹H‐ and ¹³C‐NMR spectra of purified material remained rather inconclusive with respect to both purity and constitution. The versatile access to the novel, differentially functionalized 3,3′,5,5′‐tetrabromo‐1,1′‐biphenyl platforms should ensure their wide use in future supramolecular construction.     

基于(R)-1,1’-联萘硫脲的手性荧光受体: 合成与手性识别

Two chiral fluorescent receptors 1 and 2 based on (R)-1,1‘-binaphthylene-2,2‘-bisthiourea were synthesized, and their chiral recognition properties for enantiomeric mandelate anions were studied by fluorescence spectra and molecular modeling. Addition of the L- and D-mandelate anions caused considerable fluorescent increases in the fluorescent intensity of the host solution. The L-enantiomer can enhance the fluorescence intensity of 1 much more than the D-enantiomer can do, and 1 shows a better enantioselective recognition ability than 2.     

Oxydative Aryl-Aryl-Verknüpfung von 6,6′,7,7′-Tetramethoxy-1,1′,2,2′,3,3′,4,4′-octahydro-1,1′-biisochinolin-Derivaten

Oxidative Aryl-Aryl-Coupling of 6,6′,7,7′-Tetramethoxy-1,1′,2,2′,3,3′,4,4′-octahydro-1,1′-biisoquinoline Derivatives We describe the synthesis of 2 by intramolecular oxidative coupling of 1, 1′-biisoquinoline derivatives 1 (Scheme 1). This heterocyclic system can be considered as a union of two apomorphine molecules and may thus exhibit dopaminergic activity. - The readily available tetrahydrobiisoquinoline 6 was methylated to 11 (Scheme 4) and reduced (with NaBH₃CN) to rac- 7 and (catalytically) to meso- 7 (Scheme 3). Reduction of 11 with NaBH₄ and of the biurethane rac- 9 with LiAlH₄/AlCl₃ afforded meso- and rac- 10 , respectively (Scheme 4). Demethylation of 6 , meso- 10 , meso- and rac- 7 led to 12 , meso- 14 , meso- and rac- 13 , respectively (Scheme 5). The latter two phenols were converted with chloroformic ester to the hexaethoxycarbonyl derivatives meso- and rac- 15 and subsequently saponified to the biurethanes meso- and rac- 16 , respectively (Scheme 5). - In order to assure proximity of the two aromatic rings, the ethano-bridged derivatives meso- and rac- 18 were prepared by condensing meso- and rac- 7 with oxalic ester and reducing the oxalyl derivatives meso- and rac- 17 with LiAlH₄/AlCl₃, respectively (Scheme 6). The ¹H-NMR, spectra at different temperatures showed that rac- 18 populated two conformers but rac- 17 only one, all with C₂-symmetry, and that meso- 17 as well as meso- 18 populated two enantiomeric conformers with C₁-symmetry. Whereas both oxalyl derivatives 17 were fairly rigid due to the two amide groupings, the ethano derivatives 18 exhibited coalescence temperatures of -20 and 30°. - The intramolecular coupling of the two aromatic rings was successful under ‘non-phenolic oxidative’ conditions with the tetramethoxy derivatives 7, 10 and 18 , the rac-isomers leading to the desired dibenzophenanthrolines, the meso-isomers, however, mostly to dienones (Scheme 9): With VOF₃ and FSO₃H in CF₃COOH/CH₂Cl₂ rac- 7 was converted to rac- 19 , rac- 18 to rac- 21 and rac- 10 to a mixture of rac- 20 and the dienone 23b of the morphinane type. Under the same conditions meso- 10 was transformed to the dienone 23a of the morphinane type, whereas meso- 18 yielded the dienone 24 of the neospirine type, both in lower yields. The analysis of the spectral data of the six coupling products offers evidence for their structures. With the demethylation of rac- 20 and rac- 21 to rac- 25 and rac- 26 , respectively, the synthetic goal of the work was reached, but only in the rac-series (Scheme 10). - In the course of this work two cleavages of octahydro-1,1′-biisoquinolines at the C(1), C(1′)-bond were observed: (1) The biurethanes 9 and 16 in both the meso- and rac-series reacted with oxygen in CF₃COOH solution to give the 3,4-dihydroisoquinolinium salts 27 and 28 ; the latter was deprotonated to the quinomethide 30 (Scheme 11). (2) Under the Clarke-Eschweiler reductive-methylation conditions meso- and rac- 7 were cleaved to the tetrahydroisoquinoline derivative 32 .     

Deracemization of a Macrocyclic 1,1′‐Biisoquinoline

The macrocyclic biisoquinoline 14 was synthesized in just four preparative steps starting from the simple biscarboxaldehyde 8 . The interaction with camphorsulfonic acid induces an acid‐catalyzed partial deracemization.     

1,1′‐Nitramino‐5,5′‐bitetrazoles

1,1′‐Dinitramino‐5,5′‐bitetrazole and 1,1′‐dinitramino‐5,5′‐azobitetrazole were synthesized for the first time. The neutral compounds are extremely sensitive and powerful explosives. Selected nitrogen‐rich salts were prepared to adjust sensitivity and performance values. The compounds were characterized by low‐temperature X‐ray diffraction, IR and Raman spectroscopy, multinuclear NMR spectroscopy, elemental analysis, and DTA/DSC. Calculated energetic performances using the EXPLO5 code based on calculated (CBS‐4M) heats of formation and X‐ray densities support the high performances of the 1,1′‐dinitramino‐5,5′‐bitetrazoles as energetic materials. The sensitivities toward impact, friction, and electrostatic discharge were also explored. Most of the compounds show sensitivities in the range of primary explosives and should only be handled with great care!     

Colchicine models: Synthesis and Antitubulin Activity of 2′-Monosubstituted and 2′, 5-Disubstituted 2,3,4,4′-Tetramethoxy-1,1′-biphenyls. Synthesis of 4,4′, 5′, 6′-tetramethoxy-1,1′-biphenyl-2,3′-dicarboxylic acid

Reductive amination of 2,3,4,4′-tetramethoxtybiphenyl-2-carbaldehyde ( 4 ) with MeNH₂ afforded methylamine 5 (Scheme 1), Hydroxymethylation of amine 8 , prepared similarly from 4 by reductive amination with benzylamine followed by N-methylation, afforded alcohol 12 which was converted the 5-methyl-substituted methylamine 14 by conventional chemical reactions (Scheme 2), Methylamine 14 was also obtained from ester 16 after hydroxymethylation to alcohol 17 and conventional manipulation of alcohol and ester functions (Scheme 2). Both amines 5 and 14 as well as the 2′, 5-dimethyl-substituted biphenyl 26 prepared from the dialdehyde 25 by a Wolff-Kishner reduction, did not show noteworthy activity in the tubulin binding assay or as inhibitors of tubulin polymerization (Table). However, the 2′ethyl-substituted biphebyl 11 prepared from 4 by reaction with MeLi followed by dehyderation and catalytic reduction of styrene 10 (Scheme 1) showed appreciable activity in both assays, coming close to that of known phenyltropolone models. The X-ray analysis of 14 ·HCl and 11 showed significant difference in the orientation of the rings with respect to one another (Fig.).     

Magnetic susceptibility of 1,1′,2,2′-tetramethylcobaltocene and 1,1′-diethylcobaltocene: Evidence for the dynamic Jahn-Teller effect

The magnetic susceptibility of 1,1′,2,2′-tetramethylcobaltocene, Co[C₅H₃(CH₃)₂]₂, and 1,1′-diethylcobaltocene, Co(C₅H₄C₂H₅)₂, has been studied between 0.99 and 296 K. The data are well reproduced by a calculation of the dynamic Jahn-Teller effect for the ²E_1g(a_1g²e_2g⁴e_1g) ground state of D_5d symmetry. A suitable set of parameter values is given by ζ = 100 cm⁻¹, δ = 150 cm⁻¹, k_JT = 0.40, κ = 0.70. The magnetism of cobaltocene, Co(C₅H₅)₂, may be described by parameter values of comparable magnitude. The results imply a significantly larger reduction of the spin-orbit coupling parameter ζ due to covalency than of the orbital reduction factor κ.     

Synthesis,Structure and Photochemical Properties of 4, 4′, 7, 7′-Tetra-substituted 1,1′, 3,3′-Tetraethylbenzimidazolotriazatrimethine Cyanines

The synthesis of sterically hindered 1,1′, 3,3′-tetraethylbenzimidazolotriazatrimethine cyanine dyes, their electron absorption spectra and that of their photo-products (inverse photochromism) is described. Kinetic data of the thermally reversed reaction of the photo-bleached compounds are given. The differences of the electron absorption spectra in this series in this series of dyes are explained by the different degree of distortion of the π-systems which is confirmed by an X-ray investigation.     

Stereoselective Synthesis of 1,1′‐Disaccharides by Organoboron Catalysis

The highly stereoselective synthesis of 1,1′‐disaccharides was achieved by using 1,2‐dihydroxyglycosyl acceptors and glycosyl donors in the presence of a tricyclic borinic acid catalyst. In this reaction, the complexation of the diols and the catalyst is crucial for the activation of glycosyl donors, as well as for the 1,2‐cis‐configuration of the products. The anomeric stereochemistry of the glycosyl donor depends on the employed glycosyl donor. Applications of the produced 1,1′‐disaccharides are also described.     

Synthesis and property of soluble poly(1,1′-dialkyl-3,3′-ferrocenylenevinylene)s via titanium-induced dicarbonyl-coupling reaction of 1,1′-dialkylferrocene-3,3′-dicarbaldehydes

1,1′-Dialkylferrocene-3,3′-dicarbaldehydes ( 1a–c ) with long alkyl chains such as ethyl, hexyl, and dodecyl groups were prepared in 13–25% yield via three-step reactions. The titanium-induced dicarbonyl-coupling reaction of 1a–c gave poly(1,1′-dialkyl-3,3′-ferrocenylenevi-nylene)s ( 2a–c ) in quantitative yields, which were the molecular weights of 3000–10,000 and highly soluble in chloroform, benzene, and hexane. The electrical conductivity and the third-order nonlinear optical susceptibility for poly(1,1′-dihexyl-3,3′-ferrocenylenevinylene) ( 2b ) were estimated to be 1 × 10^?2 S/cm on doping with iodine and 1–4 × 10^?12 esu at a wavelength of 1–2.4 μm, respectively. © 1995 John Wiley & Sons, Inc.     

3,3′-Oxybispyridine and the polarographic reduction of 1,1′-dimethyl-3,3′-oxybispyridinediium diiodide

3,3′-Oxybispyridine is prepared by reaction of 3-hydroxypyridine with 3-bromopyridine and converted to the 1,1′-dimethyl diquaternary salt with methyl iodide. The salt is reduced polarographically by a one electron transfer not involving hydrogen to an unstable radical cation at a potential (E_o) of ?0.81 V in the pH range 6.3-12.0.