六～八元瓜环与三种N-苄基取代笼状客体的相互作用

合成了3种具有对不同瓜环选择性各异的双探针N-苄基取代笼状客体, 它们分别是N-苄基六次甲基四胺盐酸盐(1), N-苄基喹啉环啶盐酸盐(2), N-苄基-1,4-二氮杂双环[2.2.1]辛烷盐酸盐(3), 利用¹H NMR和MS等方法对这些客体进行了表征. ¹H NMR显示, 六元瓜环仅对这些客体的苄基探针部分具有选择性作用, 形成作用比为1∶1的不对称包结配合物; 七元瓜环对客体1和3的苄基探针部分具有选择性作用, 形成作用比为1∶1的不对称包结配合物, 而对客体2的笼状奎宁环啶基部分具有选择性作用, 也形成作用比为1∶1的包结配合物; 八元瓜环也仅对这些客体的苄基探针部分具有选择性作用, 形成作用比为1∶2的对称包结配合物.     

Synthesis and conformational studies of peptides from new C-linked carbo-beta-amino acids (beta-Caas) with anomeric methylamino- and difluorophenyl moieties

New C-linked carbo-beta-amino acids (beta-Caas), Cbz-(S)-beta-Caa-(NHBoc)-OMe (1) and Cbz-(R)-beta-Caa-(NHBoc)-OMe (2), with an additional amine group (methylamino group of NHBoc) at the C-1 position of the lyxofuranoside side chain and Boc-(S)-beta-Caa-(diFP)-OMe (3) and Boc-(R)-beta-Caa-(diFP)-OMe (4), with a C-difluorophenyl (diFP) moiety at the anomeric position of the lyxofuranoside side chain were prepared from D-mannose. Beta-peptides [tetra- and hexapeptides] were synthesized from these beta-Caas, 'epimeric' [at the amine stereocentre (C(beta))], using the concept of 'alternating chirality' to carry out their conformational studies [NMR (CDCl(3)), CD and MD]. In the monomer design, it was envisaged that the presence of an additional amine group in 1 or 2 would help in solubilizing the peptides in water, while, the C-difluorophenyl (diFP) moiety of 3 and 4 is expected to enhance the biological activity. The peptides having 1 and 2, though could not retain their 12-10-mixed helices in water, have shown moderate activity against gram positive and gram negative bacterial strains. The peptides prepared from 3 and 4, much against our expectations, did not display any biological activity.     

A New Oxidative Conversion of Carbohydrate Benzyl Ethers to Benzoyl Esters with RuCl3-NaIO

Abstract

The benzyl group is often used in organic synthesis, especially in carbohydrate chemistry, as one of the most useful of the hydroxyl protecting groups. Benzyl ethers are stable to basic conditions and the benzyl group is removed easily by hydrogenolysis or under Birch reduction conditions. Alternatively, the benzyl ether group is oxidized to benzoyl ester and removed under basic conditions. A few oxidation methods have been reported using more than a stoichiometric amount of chromium reagents such as CrO₃-H₂SO₄ (Jones reagent)¹ or CrO₃-AcOH₂. Here we report a new and mild oxidation of benzyl ether to benzoyl ester with a catalytic amount of RuO₄ derived from RuCl₃ and NaIO₄. This method has proved effective in removing benzyl ether groups chemoselectively in the presence of benzylidene acetal and benzyl glycosidic functions.     

Structure-activity relationships of neuromedin U. IV. Absolute requirement of the arginine residue at position 7 of dog neuromedin U-8 for contractile activity

To examine the role of both Arg residues at positions 5 and 7 of dog neuromedin U-8 (d-NMU-8; pGlu1-Phe-Leu-Phe-Arg5-Pro-Arg7-Asn8-NH2) for smooth muscle contractile activity on isolated chicken crop, d-NMU-8 analogs were synthesized where either Arg residue was systematically replaced by various amino acids [X: Ala, Thr, Glu, Gln, Lys, Orn, His, citrulline (Cit) or homoarginine (Har)]. All [X5]-d-NMU-8, except for [Glu5]- and [Des-Arg5]-d-NMU-8, were full agonists, although their affinities to NMU receptors were decreased. No [X7]-d-NMU-8 showed contractile activity even at concentrations of 10(-5) mol/l, except for [Har7]-d-NMU-8, which retained weak biological activity. These analogs had no antagonistic activity against porcine neuromedin U-8 (p-NMU-8). The results revealed that Arg7 of d-NMU-8 is indispensable for receptor binding and activation to induce smooth muscle contraction, and the guanidino group of the side chain at position 7, but not at position 5, is strictly recognized by NMU receptors in the chicken crop.     

Regioselective Synthesis and Inclusion Properties of distal-Bis[(2-pyridylmethyl) oxy]tetrathiacalix[4]arenes

Regioselective synthesis of bis[(2-pyridylmethyl)oxy]tetrathiacalix[4]arenes was accomplished by a protection–deprotection method using benzyl groups as a protecting group. The conformational studies of distal-bis[(2-pyridylmethyl)oxy]thiacalix[4]arenes in solution and solid state are described. The two-phase solvent extraction data indicated that bis[(2-pyridylmethyl)oxy]tetrathiacalix[4]arenes show strong Ag⁺ (E%, 97%) affinity. In contrast, no significant E% is observed for K⁺. A good Job plots proves 1:1 coordination of 1,3-alternate -3 with Ag⁺ cation. ¹H-NMR Titration of 1,3-alternate- 3 with AgSO₃CF₃ also clearly demonstrates that a 1:1 complex is formed with retention of the original symmetry. The conformational changes of pyridine moiety from the original outward orientation of the ring nitrogen to the inside orientation toward the thiacalixarene cavity were observed in the process of Ag⁺ complexation. The down-field shifts of the benzene protons of the benzyl group were also observed and attributed to the conformational deviation from the original face to face overlapping.     

Benzyl cobaloximes with thiodioximes: Synthesis, structure and reactivity

Five benzyl cobaloximes with different thiodioximes, BnCo[d(SR)gH]₂Py, have been synthesized and four of these complexes have been characterized by X-ray. The reactivity of these complexes towards molecular oxygen has been studied. The puckering of the Co(dioxime)₂ unit, caused by dioxime side chain, the SR group, significantly influences the Co-C bond reactivity. Structural features in one of the oxygen inserted cobaloximes have been studied to confirm if puckering of dioxime is the guiding factor. The reactivity is also affected, to some extent, by the C-H…π interaction between the benzyl and the dioxime moiety.     

Carcinolytic peptides with selective action

Summary Peptides bearing the bis(2-chloroethyl)amino group were obtained by the catalytic hydrogenolysis of the corresponding benzyl esters.For the first communication in this series see [1–4].     

Detection and spectral analysis of trifluoromethyl groups at a surface by sum frequency generation vibrational spectroscopy

Sum frequency generation (SFG) vibrational spectroscopy was used to detect the presence of trifluoromethyl groups on the surface of 4-(trifluoromethyl)benzyl alcohol (TFMBA) in air. Supplementary data from infrared and Raman spectra were correlated to ab initio calculations by use of density functional theory (DFT) for TFMBA and three related compounds to reliably assign vibrational modes to the spectra. It was shown that strongly ordered CF3 groups dominate the surface of the TFMBA, and the vibrational modes of this functional group are strongly coupled to the benzene ring of the benzyl alcohol. This coupling, along with the SFG activity of the CF3 group, is removed with the insertion of an oxygen atom between the CF3 group and the benzene ring.     

Modified polysulfones. VI. Preparation of polymer membrane materials containing benzimine and benzylamine groups as precursors for molecularly imprinted sensor devices

A modified polysulfone containing benzylamine groups was synthesized as a reactive membrane material. Polysulfone was activated at the ortho‐sulfone site by direct lithiation with n‐butyllithium, and the resulting lithiated polysulfone was then reacted with benzonitrile; this yielded a polymer with pendant benzimine groups. The structure was confirmed by NMR and IR spectroscopy and by the transformation of imine to ketone by acid hydrolysis. The polymeric benzimine was also reduced to benzylamine with sodium cyanoborohydride in an acidic medium. The structure and degree of substitution of both benzylamine derivatives were determined by NMR and IR spectroscopy. The modified polysulfone containing benzylamine groups initiated the polymerization of N‐carboxyanhydride of γ‐benzyl‐L ‐glutamate [Glu(OBzl)–NCA]. The side‐chain oligopeptide of Glu(OBzl)–NCA attached to polysulfone was converted into molecular recognition sites. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 1316–1329, 2003     

Isolation, structural elucidation, and biosynthesis of 15-norlankamycin derivatives produced by a type-II thioesterase disruptant of Streptomyces rochei

Lankamycin, a 14-membered macrolide antibiotic, contains a 3-hydroxy-2-butyl side chain at C-13. To analyze the function of lkmE, which encodes type-II thioesterase in the lankamycin cluster, we carried out a gene disruption experiment. Disruption of lkmE resulted in a 70% decrease of lankamycin production concomitant with an accumulation of novel lankamycin derivatives (LM-NS01A and LM-NS01B), in which the C-13 side chain is replaced by a 1-carboxyethyl group. The biosynthetic origin of 1-carboxyethyl group was confirmed by incorporation of deuterium in [3-²H]3-methyl-2-oxobutyrate into the C-14 position. These results indicate that the biosynthesis of LM-NS01A and LM-NS01B starts from isobutyryl CoA in place of (S)-2-methylbutyryl CoA and LkmE removes the aberrantly loaded starter unit and restores lankamycin production.     

Synthesis and study of mesogenic compounds having a methylene ketone (-CH2-CO-) linking group

Abstract

Recently we have reported isoflavone derivatives as potential mesogens [1]. During the synthesis of isoflavone derivatives, 2,4-dihydroxyphenyl benzyl ketone was synthesized as an intermediate. Nguyen Huu Tinh et al. [2] have reported the effect of the influence of the central linkage, such as ethylene, methylene ketone and ketone on the mesogenic compounds. Vora et al. [3] have also reported a mesogenic homologous series with terminal and lateral phenolic groups. To understand the effect of hydrogen bonding originating between methylene ketone and free lateral hydroxy groups, ortho to the methylene ketone group, on mesogenicity, the present homologous series of 2-hydroxy, 4(4′-n-alkoxybenzoyloxy)phenyl benzyl ketone was synthesized. The synthesized compounds were characterized by elemental analysis and spectroscopic techniques. The first six homologues of the present series are non-mesogenic and mesomorphism appears from the heptyl derivative onwards. The present series shows a monotropic smectic A phase except for the last member (octadecyloxy) which exhibits an enantiotropic smectic A mesophase. The transition temperatures are also identified using DSC. The fluorescent studies of some of the compounds of the present series are under investigation.     

Synthesis, Conformational Studies and Inclusion Properties of Tetrakis[(2-pyridylmethyl)oxy]thiacalix[4]arenes

An attempted O-alkylation of the flexible macrocycle 1with 2-(chloromethyl)pyridine in the presence of Cs₂CO₃ under THF reflux afforded a mixture of twoconformers of tetra-O-alkylated product 4a in a ratio of 91:9 (cone-4a:1,2-alternate-4a)in 70% yield, while other possible isomers were not observed. In the case of Na₂CO₃, there was no reaction product,only the starting compound 1, whereasonly monoalkylated compound 3 was obtained when usingK₂CO₃ as the base. The distribution of cone conformer decreased in the case of O-alkylation of tetraol 1with 4-(chloromethyl)pyridine or benzyl bromide in the presence of Cs₂CO₃ in comparison with that ofO-alkylation with 2-(chloromethyl)pyridine, while the 1,2-alternate conformer increased in the same sequence. The larger Cs⁺might increase the contribution of the metal template effect, which can hold the 2-pyridylmethyl group(s) and theoxide group(s) on the same side of the tetrathiacalix[4]arene 1 through the cation-O^- and -N-interaction in the caseof O-alkylation of tetraol 1 with 2-(chloromethyl)pyridine.Only when the template metal can hold the 2-pyridyl group(s) andthe oxide group(s) on the same side of the tetrathiacalix[4]arene is the conformation immobilized to thecone. The template effect of the cesium cation plays an important role in this alkylation reaction. The structuralcharacterization of these products is also discussed.The two-phase solvent extraction data indicated thattetrakis[(2-pyridylmethyl)oxy]thiacalix[4]arenes 4a show strong Ag⁺ affinity and a high Ag⁺ selectivity wasobserved for cone-4a. A good Job plot proves 1:1 coordination of cone-4a with Ag⁺ cation.¹H-NMR titration of cone-4a with AgSO₃CF₃ also clearly demonstrates that a 1:1complex is formed with retention of the original symmetry. In contrast, the 1,2-alternate-4a can form a 2:1 metal/thiacalix[4]arene complex and the two metal-binding sites display positive allostericity. The conformational changes ofpyridine moiety from the original outward orientation of the ring nitrogen to the inside orientation toward thethiacalixarene cavity were observed in the processof Ag⁺ complexation.     

The Synthesis of the 2′′- and 2′′′-Monodeoxygenated Analogues of β-Maltosyl-(1→4)-Trehalose

Abstract

Two derivatives of β-maltosyl-(1→4)-trehalose monodeoxygenated at C-2′′ or C-2′′′ have been synthesized in [2+2] block syntheses. O-(2,3,4,6-Tetra-O-benzyl-α-D-glucopyranosyl)-(1→4)-3,6-di-O-benzyl-1,2-di-O-acetyl-β-D-glucopyranose (6), prepared from the respective orthoester, was coupled to the glycosyl acceptor 2,3-di-O-benzyl-4,6-O-benzylidene-α-D-glucopyranosyl 2,3,6-tri-O-benzyl-α-D-glucopyranoside. In the resulting tetrasaccharide 8, the only ester group was removed and replaced by a xanthate which was reduced in a Barton-McCombie reaction to afford the 2′′-deoxygenated tetrasaccharide 12. For the synthesis of a 2′′′-deoxygenated derivative, a maltose building block was assembled from two monosaccharides. The key building block was ethyl 2,3,6-tri-O-benzyl-1-thio-β-D-glucopyranoside (14) which was used i) as a glycosyl acceptor in a phenylselenyl chloride mediated coupling reaction with tri-O-benzyl-glucal and ii) after the first coupling as a glycosyl donor to react with glycosyl acceptor 7 to give tetrasaccharide 18. The phenylselenyl group was reduced with tributyltin hydride on the disaccharide level. Deprotection of 18 furnished the 2′′′-deoxy-maltosyl-(1→4)-trehalose 20.     

The Synthesis of the 2- and 2′-Monodeoxygenated Analogues of β-Maltosyl-(1→4)-Trehalose 1

Abstract

Two derivatives of β-maltosyl-(1→4)-trehalose monodeoxygenated at C-2 or C-2′ have been synthesized in [2+2] block syntheses. N-Iodosuccinimide-mediated coupling of tetra-O-benzyl-glucose to tri-O-acetyl-D-glucal followed by O-acetylation furnished 3,4,6-tri-O-acetyl-2-deoxy-2-iodo-α-D-mannopyranosyl 2,3,4,6-tetra-O-benzyl-α-D-glucopyranoside (7), which was used as a starting material for both tetrasaccharides. For the preparation of the 2′-monodeoxygenated saccharide the deoxyiodo pyranose moiety of 7 was further elaborated by de-O-acetylation, O-benzylidenation, O-benzylation, and selective reductive opening of the benzylidene acetal to give glycosyl acceptor 10. Glycosylation with hepta-O-acetylmaltosyl bromide and deprotection including removal of the iodo substituent afforded the 2′-deoxymaltosyl-(1→4)-trehalose 14. On the other hand, the non-iodinated pyranose moiety of 7 was transformed to a glycosyl acceptor. The removal of the benzyl groups of 7 necessitated also the reduction of the iodo group at this early stage. The resulting 3,4,6-tri-O-acetyl-2-deoxy-α-D-arabino-hexopyranosyl α-D-glucopyranoside was subjected to a similar reaction sequence as above to finally result in the 2-deoxymaltosyl-(1→4)-trehalose 22.

     

Synthesis of 1-Aminoalkanephosphonic and Phosphonous Acids Bearing Furan Moiety

Abstract

Synthesis of a series of 1 -aminoalkanephosphonic acids bearing hran moiety was performed, starting from the preparation[I] of various N-substituted aminophosphonic esters. We were encouraged by previous Boduszek's study [2].     

Synthesis and biological evaluation of tamandarin B analogues

[structure: see text]. The synthesis of two tamandarin B analogues in which the N,O-Me2Tyr5 unit was replaced by N-Me-phenylalanine (N-MePhe5) and (S)-2-(methylamino)-3-(naphthalen-2-yl)propanoic acid (N-MeNaphth5) is described. The choice of the macrocyclization site was crucial to achieve satisfactory macrolactamization. Coupling between norstatine (Nst1) and threonine (Thr6) afforded only a 15% yield, while lactamization between proline (Pro4) and the aromatic moiety could be achieved in 65% yield.     

Synthesis and aldose reductase inhibitory activities of benzyl 2-oxazolecarbamate analogues.

Various analogues of benzyl 5-phenyl-2-oxazolecarbamate (1a) were synthesized, and the structure-activity relationship of these analogues as aldose reductase inhibitor was studied. The carbamate group was necessary for the inhibitory activity. The introduction of an alkyl group at the C-4 position of 1a enhanced the inhibitory activity, however, the N-carboxymethyl group on the carbamate moiety counteracted to a hydrophobic interaction between the alkyl group at the C-4 position and the enzyme molecule.     

Liquid-Crystalline Polyurethanes. 5. Polyurethanes Containing the Cholesterol Moiety in the Side Chain

In the preceding papers of this series, we reported the synthesis of liquid-crystalline polyurethanes containing mesomorphic moieties in the main chain and in side chains [1–4]. Liquid crystalline polymers with side groups containing the cholesterol moiety have also been studied [5, 6]. The main focus of attention has centered around the study of phase transitions of acrylic and methacrylic derivatives of cholesterol. This paper describes the synthesis of a new type of liquid-crystalline polyurethane containing the cholesterol moiety in side chains.     

Synthesis and spectral studies on Ni(II) complexes involving N-furfuryl-N-substituted benzyldithiocarbamates and PPh3: Anagostic and C–H…π(chelate) interactions in (N-furfuryl-N-(4-fluorobenzyl)dithiocarbamato-S,S′)(thiocyanato-N)(triphenylphosphine)nickel(II)

Twelve new nickel(II) complexes of functionalized dithiocarabamates [Ni(S₂CNRR')₂](1-6) and [Ni(S₂CNRR')(NCS)(PPh₃)](7-12) [where R=furfuryl; R'=2-hydroxy benzyl (1,7), 3-hydroxy benzyl (2,8), 4-hydroxy benzyl (3,9), 4-methoxy benzyl (4,10), 4-fluoro benzyl (5,11), 4-chloro benzyl (6,12)] have been prepared and characterized by elemental analysis, IR, UV-Vis and NMR (¹H and ¹³C) spectroscopy. IR spectra of the complexes support the bidentate coordination of dithiocarbamate ligands. Electronic spectral studies on complexes 1-12 indicate square planar geometry around the nickel(II) central atom. In the ¹³C NMR spectra, the upfield shift of NCS₂ carbon signal for heteroleptic complex (7-12) compared to homoleptic complexes (1-6) is due to the effect of PPh₃ on the mesomeric drift of electron density toward nickel through thioureide C-N bond. Single crystal X-ray structural analysis of complex 11 confirms that the coordination geometry about the Ni(II) is distorted square planar. A rare intramolecular anagostic interaction C–H^…Ni [Ni???H=2.804 Å] is observed. The packing of complex 11 is stabilized by non-conventional C–H^…S, C–H?F and C–H?π(chelate, NiS₂C) bonding interactions.     

Synthesis and properties ofN-substituted azacalix[n]arenes

Side arm modifications of hexahomotriazacalix[3]arene (1) were achieved by simple synthetic methods. Compound5 has picolyl side arms and liquid-liquid extraction experiments showed that the alkali cation affinity of5 is much stronger than that of1. A chiral group was also introduced into the azacalixarene structure. Calix[4]arene was converted into dihomoazacalix[4]arene (2) in 8% yield. Clathrate formation of2 with various solvents is described. MM3 calculations were carried out onp-substituted analogs of2. The self-filled structure, in which the benzyl side arm is placed in its cavity, is the most stable structure when thep-positions of the aromatic rings carry small substituents. Strong hydrogen bonds between nitrogen and phenolic hydroxyl groups in dihomoazacalix[4]arene (2) were observed at low temperatures. The¹H-NMR signals of phenolic hydroxyl groups appeared as six singlets in the range of 9.817.1 ppm at –70°C.This paper is dedicated to the commemorative issue on the 50th anniversary of calixarenes.