Templating Irreversible Covalent Macrocyclization by Using Anions

Inorganic anions were used as templates in the reaction between a diamine and an activated diacid to form macrocyclic amides. The reaction conditions were found to perform the macrocyclization sufficiently slow to observe a template effect. A number of analytical methods were used to clarify the reaction mechanisms and to show that the structure of the intermediate plays a decisive role in determining the product distribution. For the macrocyclization under kinetic control, it was shown that the amount of a template, the conformational rigidity of building blocks, and the anion affinities of reaction components and intermediates are important parameters that one should take into consideration to achieve high yields.     

Templated synthesis of glycoluril hexamer and monofunctionalized cucurbit[6]uril derivatives

We report that the p-xylylenediammonium ion (11) acts as a template in the cucurbit[n]uril forming reaction that biases the reaction toward the production of methylene bridged glycoluril hexamer (6C) and bis-nor-seco-CB[10]. Hexamer 6C is readily available on the gram scale by a one step synthetic procedure that avoids chromatography. Hexamer 6C undergoes macrocylization with (substituted) phthalaldehydes 12, 14, 15, and 18-in 9 M H(2)SO(4) or concd HCl at room temperature to deliver monofunctionalized CB[6] derivatives 13, 16, 17, and 19-that are poised for further functionalization reactions. The kinetics of the macrocyclization reaction between hexamer and formaldehyde or phthalaldehyde depends on the presence and identity of ammonium ions as templates. p-Xylylenediammonium ion (11) which barely fits inside CB[6] sized cavities acts as a negative template which slows down transformation of 6C and paraformaldehyde into CB[6]. In contrast, 11 and hexanediammonium ion (20) act as a positive template that promotes the macrocyclization reaction between 6C and 12 to deliver (±)-21 as a key intermediate along the mechanistic pathway to CB[6] derivatives. Naphthalene-CB[6] derivative 19 which contains both fluorophore and ureidyl C═O metal-ion (e.g., Eu(3+)) binding sites forms the basis for a fluorescence turn-on assay for suitable ammonium ions (e.g., hexanediammonium ion and histamine).     

Stereoselective reactions of a (-)-quinic acid-derived enone: application to the synthesis of the core of scyphostatin

[reaction: see text] A (-)-quinic acid-derived enone, with the trans-1,2-diol protected as a 2,3-dimethoxybutanediyldioxy ketal, provides an excellent template for further highly stereoselective elaboration as exemplified by its conversion into the core of scyphostatin, a potent inhibitor of neutral sphingomyelinase.     

Synthesis of New Multibenzo Oxygen–Sulfur Donor Macrocycles Containing Lactams at Room Temperature

Some new oxygen–sulfur, multibenzo macrocyclic ligands containing amide groups have been prepared using the macrocyclization process with the reaction of 2,2′-thiobis-[4-methyl(2-aminophenoxy)phenyl ether] as a symmetrical diamine with appropriate dicarboxylicacid dichlorides in moderate yields. This macrocyclization led to the formation of di- and tetramide macrocycles. These reactions were routinely carried out at ambient temperature in CH₂Cl₂ as solvent in high dilution without template effect conditions. It is found that sulfur the atom affects the rigidity of the macrocycles and diastereotopicity of nuclei in the ring of these series of macrocyclic compounds.     

Quantitative evaluation of the chloride template effect in the formation of dicationic [1(4)]imidazoliophanes

The formation of macrocycles containing two imidazolium rings such as 1.2X and 2.2X is anion-directed through hydrogen bonding. The template effect exerted by the chloride anion in the ring-closure reaction of the monocationic model intermediate 9+ to yield the [1(4)]imidazoliophane 2(2+) has been evaluated. This effect was quantified following the kinetics of the macrocyclization by using a UV-vis technique. The rate of the ring closure of monocation 9+ is increased up to 10 times, in the presence of Bu4NCl 0.04 M. This finding confirms that the template effect is operative in the macrocyclization leading to dicationic [1(4)]imidazoliophanes.     

Photoisomerizable azobenzene-containing oxacalixarenes

The first examples of photo-responsive azobenzene-containing oxacalixarenes have been synthesized via a 3+1 macrocyclization approach. Introduction of the photoresponsive unit was achieved by using 4-phenylazoresorcinol or (E)-4-(4′-nitrophenylazo)resorcinol as the nucleophilic component in the macrocyclization reaction. These novel macrocycles have been characterized by means of 1D and 2D NMR spectroscopy and DFT calculations (B3LYP/6-31G(d)). According to thermal and photoisomerization studies, tetranitro-oxacalix[4]arenes are less prone to E→Z isomerization than oxacalix[2]arene[2]triazines and, within the two series, p-nitrophenylazo derivatives are more unwilling to isomerize than their phenylazo analogues.     

A [2]catenane containing an upper-rim functionalized calix[4]arene for anion recognition

A novel [2]catenane is synthesized in good yield from an upper-rim functionalized calix[4]arene macrobicycle and a nitro-substituted isophthalamide threading component in the presence of a chloride anion template via a ring-closing metathesis (RCM) reaction. After halide anion template removal the resulting catenane host exhibits a high degree of selectivity for chloride in competitive organic solvent mixtures.     

硅钨酸掺杂的聚苯胺：实物模板法制备及催化性能

以不同形态的实物为模板,硅钨酸为掺杂剂,过硫酸铵为氧化剂合成了不同微观形貌掺杂态聚苯胺,并用红外光谱、气相色-质联用仪及扫描电镜对其进行了表征。考察了所制备的聚苯胺催化合成环己酮1,2-丙二醇缩酮的性能,探讨了不同微观形貌掺杂态聚苯胺催化剂对缩酮反应的催化活性,研究了催化剂用量、反应时间等因素对产品收率的影响,以及不同沸程的产物。结果表明:硅钨酸掺杂聚苯胺是合成环己酮1,2-丙二醇缩酮的良好催化剂,其中微观结构为球状的聚苯胺催化性能最佳。在n环己酮∶n1,2-丙二醇=1∶1.4,催化剂用量为反应物总质量的1.6%,反应时间为40 min的最佳条件下,环己酮1,2-丙二醇缩酮的收率为89.2%。     

Free-standing aluminium nanowire architectures made in an ionic liquid

We report on the electrochemical synthesis of free‐standing aluminium nanowire architectures through a template‐assisted electrodeposition technique. For this purpose, nuclear track‐etched polycarbonate membranes were employed as templates. One side of the template was sputtered with a thin gold film to serve as a working electrode. Subsequently the nanowires were made in the ionic liquid 1‐ethyl‐3‐methylimidazolium chloride ([EMIm]Cl)/AlCl₃ (40/60 mol %) under potentiostatic conditions. Two different electrodeposition procedures were employed to fabricate strongly adherent Al nanowire structures on an electrodeposited Al layer. In the first procedure, electrodeposition simultaneously occurs along the pores of the template and on the Au‐sputtered side of the template. In the second procedure, electrodeposition takes place in two different steps: first a thick supporting film of Al is deposited on the sputtered side of the membrane and second Al nanowires are grown within the pores. After chemical dissolution of the membrane in dichloromethane, an aluminium foil of a controlled thickness with a three‐dimensional nanowire structure on one side was obtained. Different nanowire architectures, such as free‐standing nanowires, vertically aligned tree‐shaped arrays, and bunched nanowire films, were obtained. Such nanowire architectures are of particular interest for applications in Li‐ion micro‐batteries.     

Nitrite‐Templated Synthesis of Lanthanide‐Containing [2]Rotaxanes for Anion Sensing

The first anion‐templated synthesis of a lanthanide‐containing interlocked molecule is demonstrated by utilizing a nitrite anion to template initial pseudorotaxane formation. Subsequent stoppering of the interpenetrated assembly allows for the preparation of a lanthanide‐functionalized [2]rotaxane in high yield. Following removal of the nitrite anion template, the europium [2]rotaxane host is demonstrated to recognize and sense fluoride selectively.     

Supramolecular control of the template-induced selective photodimerization of 4-methyl-7-O-hexylcoumarin

A symmetric ditopic molecular receptor (3), containing two identical hydrogen-bonding recognition subunits, was designed and synthesized. These subunits are capable of binding substrates with complementary donor and acceptor sites to form a supramolecular complex through hydrogen bonding. Receptor 3 was designed to accept two guest molecules, which are held in close proximity within the supramolecular species. The substrate molecule, 4-methyl-7-O-hexylcoumarin (1 c), forms a 2:1 complex with a binding constant of 150 m(-1) for the second substrate, passing first through a 1:1 complex with an affinity constant of 510 m(-1). The orientation of two molecules of 1 c when bound to the template leads to the selective formation of the trans-syn [2+2] photoproduct 2 cB upon irradiation. Other photoproducts typically produced in the absence of the template are suppressed.     

Differential EI fragmentation pathways for peracetylated C-glycoside ketones as a consequence of bicyclic ketal ring structures

Several C-glycoside ketones and peracetylated C-glycoside ketones have been synthesized from 13 structurally-diverse aldoses sugars (including isotope labeled [1-(13)C]Glc, [U-(13)C]Glc, and [6, 6'-(2)H(2)]Glc) via an aqueous-based Knoevanagel condensation with aliphatic 1,3-diketones. Sodium adduct molecular ions observed by MALDI-TOF MS confirmed that the reactions are essentially quantitative, and that the acetylation products are the expected peracetylated C-glycoside ketones, rather than cyclized ketofurans. Analysis of the peracetylated C-glycoside ketones by gas chromatography-EI-MS show characteristic fragment ions that have been assigned to four distinct fragmentation pathways. Peracetylated aldohexose-, aldopentose-, and 6-deoxyaldohexose-C-glycoside ketones fragment via gas phase furanoid intermediates. These data, and DFT calculations, indicate that the furanoid intermediates arise because the peracetylated C-glycoside ketones adopt a bicyclic structure containing a 5-member ketal ring. This ketal ring is the precursor of the furanoid rings in the gas phase. The 2-deoxyhexose-C-glycoside ketones are unable to form an intramolecular 2-ketal bond, and therefore undergo ion fragmentations via nonfuranoid pathways.     

Solid-phase SN2 macrocyclization reactions to form beta-turn mimics

[formula: see text] Efficient solid-phase SN2 macrocyclization reactions were sought to facilitate preparations of focused libraries of beta-turn mimetics. A very efficient, but undesired, cyclization reaction to give five-membered ring lactams 4 was identified in attempts to use O-nucleophiles. Subsequent studies focused exclusively on S-nucleophiles. These reactions gave the desired macrocyclization products 1 in high purities and good overall yields. Conformational analyses of illustrative macrocyclization products 1 via NMR, CD, and molecular simulations showed that they seem to sample both type I and type II beta-turn conformations in solution. CD studies indicate a curious relationship between the preferred conformation and the amino acids encapsulated in the macrocycles.     

Chiral macrocyclic aliphatic oligoimines derived from trans-1,2-diaminocyclohexane

Aliphatic dialdehydes of rigid structures having a cyclohexane, a bicyclo[2.2.2]octane or a [7]triangulane skeleton, have been condensed with enantiomerically pure trans-1,2-diaminocyclohexane to give [3+3] or [2+2] macrocyclization products. Unlike acyclic aliphatic imines, these macrocyclic oligoimines show enhanced stabilities and their structures in the crystals could be determined by X-ray diffraction analyses. The enantiomerically pure [7]triangulane dialdehyde showed remarkable diastereoselectivity in the condensation with the two enantiomers of trans-1,2-diaminocyclohexane: only one of the enantiomers gave a [2+2] macrocyclization product. Circular dichroism measurements combined with computational analysis show that the lowest energy electronic transition in these cyclic oligoimines is of n-pi* type.     

Transannular Diels-Alder studies on the asymmetric total synthesis of chatancin: the pyranophane approach

[reaction: see text] A pathway is proposed for the biosynthesis of (+)-chatancin and (+)-sarcophytin linking these tetracycles to cembranoids by a pyranophane transannular Diels-Alder reaction. Preliminary synthetic results in this direction to reach macrocyclic dienedione 28 from farnesol are reported. Major synthetic steps include a Prins reaction, two enantioselective hydrogenations, and a macrocyclization via a beta-ketosulfoxide Michael-addition on an enone.     

多层核-壳结构P(AM-co-MAA)/W/UF复合微球制备研究

以反相悬浮聚合技术合成的丙烯酰胺(acrylamide,AM)和甲基丙烯酸(methacrylic acid,MAA)共聚高分子微凝胶P(AM-co-MAA)为模板,通过离心沉积法将微米级钨粉沉积于高分子微凝胶表面,得到具有核-壳结构的P(AM-co-MAA)/W复合微球材料;再以P(AM-co-MAA)/W复合微球为模板,通过控制甲醛和尿素的缩聚反应在模板与油/水相界面进行,制备得到了具有多层核-壳结构的高分子/钨/脲醛树脂[P(AM-co-MAA)/W/Urea-formaldehyde resin]复合微球材料.利用扫描电子显微镜(SEM)、红外(FT-IR)、X射线衍射(XRD)和热分析(TGA)等手段对复合微球进行了表征.实验结果表明,外壳层脲醛树脂的包覆量、复合微球的表面形貌可通过改变甲醛和尿素溶液的浓度、甲醛和尿素的物质的量之比等因素进行控制.复合微球的导电性测试结果表明,P(AM-co-MAA)/W复合微球表面壳层脲醛树脂包覆前后,其电导率由1.9×10-3降低为0.9×10-8S·m-1.该研究获得的三层核-壳复合微球材料其外层脲醛树脂的包覆较为完整、致密,其导电性接近于绝缘材料,为含钨复合微球作为电子元件的抗辐射涂层材料打下了基础.     

Synthesis of 4,5-diaryl-1H-pyrazole-3-ol derivatives as potential COX-2 inhibitors

4,5-Diaryl-1H-pyrazole-3-ol was utilized as a versatile template to synthesize several classes of compounds such as pyrazolo-oxazines 7, pyrazolo-benzooxazines 9, pyrazolo-oxazoles 10, and its analogues 11a-c as potential COX-2 inhibitors. Compounds 11b,c were successfully synthesized with use of pyridinium p-toluenesulfonate mediated cyclization of the ketal intermediate. Diaryl-pyrazolo-benzooxazepine analogues were synthesized by using Cu-mediated cyclization of the O-alkylated arylbromide intermediate. Arylsulfonamides were synthesized efficiently on a large scale with 4-[4-(4-fluorophenyl)-5-hydroxy-2H-pyrazol-3-yl]benzenesulfonamide 31 template readily synthesized from commercially available 4-sulfamoyl benzoic acid 29. The structure of a representative compound from each class was confirmed by X-ray crystallography. Selected compounds tested for inhibitory activity against COX-1 and COX-2 enzymes showed good selectivity for COX-2 versus COX-1 enzyme.     

Synthesis of IB-01211, a cyclic peptide containing 2,4-concatenated thia- and oxazoles, via Hantzsch macrocyclization

[structure: see text] An efficient and versatile convergent synthesis of IB-01211 based on a combination of peptide and heterocyclic chemistry is described. The key step in the synthesis is macrocyclization through intramolecular Hantzsch formation of the thiazole ring. Dehydration of a free primary alcohol to furnish the exocyclic methylidene present in the natural product was applied during the macrocyclization.     

Branched Multifunctional Polyether Polyketals: Variation of Ketal Group Structure Enables Unprecedented Control over Polymer Degradation in Solution and within Cells

Multifunctional biocompatible and biodegradable nanomaterials incorporating specific degradable linkages that respond to various stimuli and with defined degradation profiles are critical to the advancement of targeted nanomedicine. Herein we report, for the first time, a new class of multifunctional dendritic polyether polyketals containing different ketal linkages in their backbone that exhibit unprecedented control over degradation in solution and within the cells. High-molecular-weight and highly compact poly(ketal hydroxyethers) (PKHEs) were synthesized from newly designed α-epoxy-ω-hydroxyl-functionalized AB(2)-type ketal monomers carrying structurally different ketal groups (both cyclic and acyclic) with good control over polymer properties by anionic ring-opening multibranching polymerization. Polymer functionalization with multiple azide and amine groups was achieved without degradation of the ketal group. The polymer degradation was controlled primarily by the differences in the structure and torsional strain of the substituted ketal groups in the main chain, while for polymers with linear (acyclic) ketal groups, the hydrophobicity of the polymer may play an additional role. This was supported by the log?P values of the monomers and the hydrophobicity of the polymers determined by fluorescence spectroscopy using pyrene as the probe. A range of hydrolysis half-lives of the polymers at mild acidic pH values was achieved, from a few minutes to a few hundred days, directly correlating with the differences in ketal group structures. Confocal microscopy analyses demonstrated similar degradation profiles for PKHEs within live cells, as seen in solution and the delivery of fluorescent marker to the cytosol. The cell viability measured by MTS assay and blood compatibility determined by complement activation, platelet activation, and coagulation assays demonstrate that PKHEs and their degradation products are highly biocompatible. Taken together, these data demonstrate the utility this new class of biodegradable polymer as a highly promising candidate in the development of multifunctional nanomedicine.     

Expanding sapphyrin: towards selective phosphate binding

The anion-templated syntheses and binding properties of novel macrocyclic oligopyrrole receptors in which pyrrole rings are linked through amide or imine bonds are described. The efficient synthesis was accomplished by anion-templated [1+1] Schiff-base condensation and acylation macrocyclization reactions. Free receptors and their host-guest complexes with hydrochloric acid, acetic acid, tetrabutylammonium chloride, and hydrogen sulfate were analyzed by single-crystal X-ray diffraction analysis. Stability constants with different tetrabutylammonium salts of inorganic acids were determined by standard 1H NMR and UV/Vis titration techniques in [D6]DMSO/0.5% water solution. According to the titration data, receptors containing three pyrrole rings (10 and 12) exhibit high affinity (log Ka=5-7) for bifluoride, acetate, and dihydrogen phosphate, and interact weakly with chloride and hydrogen sulfate. The amido-bipyrrole receptors 11 and 13 with four pyrrole rings exhibit 10(4)- and 10(2)-fold selectivity for dihydrogen phosphate, respectively, as inferred from competitive titrations in the presence of tetrabutylammonium acetate.