New 2+2, 3+3 and 4+4 macrocycles derived from 1,2-diaminocyclohexane and 2,6-diformylpyridine

Two new Schiff base macrocycles - a 4+4 condensation product and a meso-type 2+2 condensation product - were obtained in a reaction of trans-1,2-diaminocyclohexane and 2,6-diformylpyridine. Reduction of these compounds led to the corresponding 4+4 and 2+2 macrocyclic amines. The macrocycles were characterised by NMR spectroscopy and electrospray mass spectrometry. The symmetry and stereochemistry of these macrocycles, as well as of new 3+3 and 4+4 diastereomers identified in solution, has been established. X-Ray structures of the 2+2 and 4+4 Schiff base macrocycles confirm the configurations determined on the basis of spectroscopic investigations. The crystal structures reveal that the centres of the square-shaped 4+4 macrocycles form channels as a result of columnar stacking.     

Efficient proton-templated synthesis of 18- to 38-membered tetraimino(amino)diphenol macrocyclic ligands: structural features and spectroscopic properties

A whole range of Robson-type tetraiminodiphenol macrocyclic ligands have been prepared as their perchlorate salts [H4L](ClO4)2 in high yield (ca. 90%) by a single-step [2 + 2] condensation reaction between 4-methyl(or tert-butyl)-2,6-diformyl(or diacyl)phenols and alpha,omega-diaminoalkanes (C2-C12) in the presence of acetic acid and NaClO4. The reduction of these 18- to 38-membered macrocyclic salts with NaBH4 have afforded corresponding tetraaminodiphenol macrocycles H2L'. The X-ray crystal structures of two of the tetraiminodiphenol macrocycles with the C2 and C4 lateral chains have been determined, and the optimized configurations for all of the macrocycles have been obtained by molecular mechanics calculations. The macrocycles have been characterized by elemental analysis and by IR, absorption, emission, and NMR spectroscopic study. The protonated tetraiminodiphenol macrocycles exhibit strong fluoroscence in methanol, acetonitrile, and nitromethane and undergo quenching when treated with triethylamine. The neutral macrocycles H2L, isolated by treating [H4L](ClO4)2 with excess of triethylamine, lack luminescence, as do the reduced tetraaminodiphenol macrocycles H2L'. The hydrolytic cleavage of [H4L](ClO4)2 has been studied.     

Synthesis of nitrogen and sulfur macrocycles with cis exogenous oxygen and sulfur donor atoms

A series of new N4 and N8 macrocycles has been prepared, that includes cis-exogenous O2, S2 and S/O atoms to allow chelation to a metal external to the macrocyclic ring. We found that thioamide units within the macrocycles were unstable to attack by secondary amines and thus alkylated precursors containing only tertiary amines could lead to exogenous-S2 macrocycles. Cyclisation of alkylated tetraamine precursors with dimethyloxalate or dithiooxamide led to both N4 and N8 macrocycles via 1 + 1 and 2 + 2 cyclisation reactions with exogenous-O2 or S2 respectively. Alkylation of preformed exogenous-O2 macrocycles was explored and led to alkyl substitution at the secondary amine nitrogens in the ring, however synthesis of these species was overall lower yielding than cyclisation using alkylated tetraamine precursors. Thionation of an exo-O2 macrocycle using an analogue of Lawesson's Reagent led to formation of the analogous exogenous-S2 and exogenous-O,S macrocycles. Related S2N2 macrocycles with exogenous-O2 were prepared by a cyclisation route but could not be isolated free of larger ring analogues.     

Synthesis of novel steroid-peptoid hybrid macrocycles by multiple multicomponent macrocyclizations including bifunctional building blocks (MiBs)

Two new groups of cholane-peptoid hybrid macrocycles were produced by implementing novel combinations of the MiB methodology. Steroid-based hybrid macrolactams including heterocycle and aryl moieties were obtained by utilizing cholanic dicarboxylic acids and diamines in a bidirectional double Ugi-Four-Component (Ugi-4CR) based macrocyclization protocol. Alternatively, N-substituted cyclocholamides were produced from a cholanic pseudo-amino acid by an Ugi-4CR-based cyclooligomerization approach. Both types of macrocycles are steroid-peptoid hybrid macrocycles containing exocyclic peptidic chains. These novel frameworks are a result of the use of bile acids bifunctionalized with carboxylic and amino functionalities as bifunctional building blocks of the Ugi-MiB approach.     

Novel enantioselective receptors for N-protected glutamate and aspartate

A series of chiral bisthiourea macrocycles 1-4 have been prepared and their binding properties with various dicarboxylate salts have been examined by using NMR titration and isothermal calorimetry experiments. Macrocycle 1, in particular, favours the 1:1 binding of N-protected L-glutamate and aspartate, but favours 1:2 binding of the corresponding D-amino acids in polar solvents (dimethyl sulfoxide and acetonitrile). The macrocycles, however, do not bind carboxylates at all in the less competitive solvent chloroform. The binding properties of these macrocyles are sensitive to small structural changes as demonstrated by the altered binding properties of macrocycles 2-4 compared with 1.     

Synthesis of macrocycles incorporating azo‐bis(azofurazan) framework

A series of macrocycles containing four furazan rings bonded by three azo bonds 2, 5 and 7 have been synthesized from the common precursor, 3‐amino‐3′‐nitro(azofurazan) 3 . The macrocycles closure is a result of N?N bond formation at oxidative cyclization of corresponding bis(3‐aminofurazan‐4‐yl) precursors. X‐Ray crystal structures of macrocycles 2, 2 ?AcOH, 11 and 13 are reported.     

Smart macrocyclic molecules: induced fit and ultrafast self-sorting inclusion behavior through dynamic covalent chemistry

A family of macrocycles with oligo(ethylene glycol) chains, 4O, 5O, and 6O, was developed to construct a series of new incorporated macrocycles through dynamic covalent chemistry. These flexible macrocycles exhibited excellent "self-sorting" abilities with diamine compounds, which depended on the "induced-fit" rule. For instance, the host macrocycles underwent conformational modulation to accommodate the diamine guests, affording [1+1] intramolecular addition compounds regardless of the flexibility of the diamine. These macrocycles folded themselves to fit various diamines with different chain length through modulation of the flexible polyether chain, and afforded intramolecular condensation products. However, if the chain of the diamine was too long and rigid, oligomers or polymers were obtained from the mixture of the macromolecule and the diamine. All results demonstrated that inclusion compounds involving conformationally suitable aromatic diamines were thermodynamically favorable candidates in the mixture due to the restriction of the macrocycle size. Furthermore, kinetic and thermodynamic studies of self-sorting behaviors of both mixed 4O-5O and 4O-6O systems were investigated in detail. Finally, theoretical calculations were also employed to further understand such self-sorting behavior, and indicated that the large enthalpy change of H(2)NArArNH(2)@4O is the driving force for the sorting behavior. Our system may provide a model to further understand the principle of biomolecules with high specificity due only to their conformational self-adjusting ability.     

卟啉衍生物复合单层膜的结构特征

四羧酸对称取代的卟啉衍生物5,10,15,20-tetra-4-oxy(aceticacid)phenylporphyrin(TAPP)及其与二甲基二(十六烷基)溴化铵(DMDHA)所形成的复合物在空气/水溶液界面上可形成稳定的单层膜,利用π-A等温线、UV-vis光谱及偏振光谱对单层膜的结构作用了研究,结果表明,纯TAPP的单层膜中,卟啉环间有强的相互作用,其间距约为0.55nm;1:1(摩尔比)的复合物单层膜中,环间距离与纯TAPP相比无明显变化,但聚集体间距离增加了;而1:4的复合物单层膜中,环与环间的相互作用减弱,环间距离及聚集体间的距离均明显增加。     

Rotaxanes of cyclic peptides

The synthesis of rotaxanes derived from the synthetic peptide macrocycles cyclo(l-ProGly)4 and cyclo(l-ProGly)5 and diammonium threads is described. [2]Rotaxanes are formed in good yields (56-63%), despite the disruption of internal amide-amide hydrogen bonding in the macrocycles.     

Solid support synthesis of 15-membered macrocycles containing a serotonin unit

Efficient assembly of 15-membered macrocycles utilizing the S_NAr of fluorine in 3-fluoro-4-nitrobenzoic acid with the OH functionality of serotonin on solid support is reported. This flexible synthesis yields a set of title macrocycles with good purity (>90%).     

Novel 1,3-dipolar cycloaddition reactions of calix[4]bis(spirodienones): synthesis of isoxazolidine derived macrocycles

Calix[4]bis(spirodienones) can perform as either 4π or 2π components in cycloaddition reactions with various carbo- and hetero-dienophiles and with 1,2-benzoquinones leading to the formation of highly functionalized macrocycles. In this Letter we report, highly regio- and stereoselective 1,3-dipolar cycloaddition reactions of a bis(spirodienone) derivative of calix[4]arene with nitrones that provide easy access to isoxazolidine derived macrocycles in excellent yields. These isoxazolidine derivatives can be considered as direct precursors of 1,3-amino alcohols.     

Imine- and Amine-Type Macrocycles Derived from Chiral Diamines and Aromatic Dialdehydes

The condensation of aromatic dialdehydes with chiral diamines, such as 1,2-trans-diaminocyclohexane, leads to various enantiopure or meso-type macrocyclic Schiff bases, including [2 + 2], [3 + 3], [4 + 4], [6 + 6] and [8 + 8] condensation products. Unlike most cases of macrocycle synthesis, the [3 + 3] macrocycles of this type are sometimes obtained in high yields by direct condensation without a metal template. Macrocycles of other sizes from this family can often be selectively obtained in high yields by a suitable choice of metal template, solvent, or chirality of the building blocks. In particular, the application of a cadmium(II) template results in the expansion of the [2 + 2] macrocycles into giant [6 + 6] and [8 + 8] macrocycles. These imine macrocycles can be reduced to the corresponding macrocyclic amines which can act as hosts for the binding of multiple cations or multiple anions.     

Utilization of achiral alkenyl amines for the preparation of high affinity Grb2 SH2 domain-binding macrocycles by ring-closing metathesis

A family of previously reported ring-closing metathesis (RCM)-derived macrocycles that exhibit potent Grb2 SH2 domain-binding affinity is characterized by stereoselectively-introduced upper ring junctions that bear bicyclic aryl substituents. However, the synthetic complexity of these macrocycles presents a potential limit to their therapeutic application. Therefore, the current study was undertaken to simplify these macrocycles through the use of achiral 4-pentenylamides as ring-forming components. A series of macrocycles (5a-f) was prepared bearing both open and cyclic constructs at the upper ring junction. The Grb2 SH2 domain-binding affinities of these macrocycles varied, with higher affinities being obtained with cyclo-substituents. The most potent analogue (5d) contained a cyclohexyl group and exhibited Grb2 SH2 domain-binding affinity (K(D) = 1.3 nM) that was nearly equal to the parent macrocycle (2), which bore a stereoselectively-introduced naphthylmethyl substituent at the upper ring junction (K(D) = 0.9 nM). The results of this study advance design considerations that should facilitate the development of Grb2 SH2 domain-binding antagonists.     

The first electroresponsive phenylazomethine macrocycles: highly preferential formation and regular molecular packing

[structure: see text] Highly preferential formation of novel polyphenylazomethine macrocycles was achieved by further addition of TiCl(4) and/or the monomer during the course of the polycondensation. These macrocycles have unique structures based on the (E)/(Z)-conformation of the azomethine bonds, the extremely regular molecular-packing state, and the reversible redox properties by protic acid doping.     

Diphenylanthracene macrocylces from reductive zirconocene coupling: on the edge of steric overload

Trimeric diphenylanthracene macrocycles were synthesized via the zirconocene-mediated coupling of 9,10-bis-[4-trimethylsilyl(ethynyl)phenyl]anthracene. The macrocycles feature a strained architecture due to orientation of the anthracene units into the plane of the macrocycle. The demetalated cyclophane exhibits a considerably higher flexibility in solution, while the zirconocene-containing macrocycle is quite rigid.     

Binuclear ruthenium macrocycles formed via the weak-link approach

The "weak-link approach" for the synthesis of metallomacrocycles has been used to synthesize a series of novel Ru(II) macrocycles in high yield. RuCl2(PPh3)3 has been reacted with two different phosphino-alkyl-ether hemilabile ligands, 1,4-(PPh2(CH2)2O)2C6H4 and 1,4-(PPh2(CH2)2OCH2)2C6H4. The hemilabile bidentate ligand coordinates to Ru(II) centers through both the P and O atoms to form bimetallic "condensed intermediates". The weak Ru-O bonds have been selectively cleaved with CO, 1,2-diaminopropane, and pyridine to yield large open macrocycles. This is the first example of the weak-link approach employed to synthesize macrocycles with Ru, and metal centers in general that have more than four coordination sites.     

Gold(I) and Gold(0) Complexes of Phosphinine-Based Macrocycles

A "CO-like matrix", showing coordination analogous to that of carbonyl groups, is provided by silacalix[4]phosphinine macrocycles. Reaction with Au(I) leads to the first gold(I) complexes of macrocycles, which can be reduced with sodium or potassium to the paramagnetic gold(0) complexes (an example is shown), as evidenced by cyclic voltammetry and EPR spectroscopy.     

Transition metal-mediated intramolecular [2+2+2] cycloisomerizations of cyclic triynes and enediynes

[reaction: see text] Nitrogen-containing 15-membered triacetylenic macrocycles known as 1,6,11-tris(arylsulfonyl)-1,6,11-triazacyclopentadeca-3,8,13-triynes (1) and enediynic macrocycles called 1,6,11-tris(arylsulfonyl)-1,6,11-triazacyclopentadeca-3-ene-8,13-diynes (4 and 5) were satisfactorily prepared. [2+2+2] cycloisomerization processes catalyzed by transition metals were tested in the above-mentioned macrocycles. Readily available and familiar cyclotrimerization precatalysts were examined for efficiency. Among them, the RhCl(CO)(PPh(3))(2) complex was found to catalyze the cycloisomerization reaction giving the desired cycloadducts in high yields.     

Anion and carboxylic acid binding to monotopic and ditopic amidopyridine macrocycles

Binding of inorganic anions, carboxylic acids, and tetraalkylammonium carboxylates by macrocyclic compounds of different size was studied by NMR in DMSO-d6. It has been shown that at least a 15-membered ring is necessary for successful recognition of fluoride. Larger macrocycles were shown to bind HSO4(-), H2PO4(-), Cl(-), and carboxylic acid salts. Effects of binding topicity are discussed. The 30-membered macrocycles 4 and 4m selectively bind substrates that are size- and shape-complementary: maximum binding is observed for dicarboxylic acids and dicarboxylates with four-carbon chains, and the binding constant for association of fumaric acid and 4 is ca. 5 orders of magnitude higher than that of maleic acid. The 30-membered macrocycle 4m showed selectivity toward alpha-ketocarboxylic acids. Secondary amino groups were not crucial for binding of fluoride to the macrocycles; however, they proved to be very important for selectivity and strength of carboxylic acid binding. The X-ray structure of the adduct of 4 and nitrobenzoic acid confirmed the guest H-bonding with both the amide and the secondary amino groups of the 30-membered macrocyclic host.     

Gold(I)-carbenes derived from 4-pyridylisocyanide complexes: supramolecular macrocycles supported by hydrogen bonds, and luminescent behavior

Monomeric gold(I) carbenes of the type [AuR[C(NR1R2)(NHPy-4)]] (Py-4 = 4-pyridyl) have been prepared with R = C6F5, Fmes (2,4,6-tris(trifluoromethyl)phenyl) by reaction of the corresponding isocyanide compounds [AuR(CNPy-4)] with primary or secondary amines. The single crystal X-ray diffraction structures of [Au(C6F5)[C(NEt2)(NHPy-4)]].OH2, [Au(Fmes)[C(NEt2)(NHPy-4)]], and [Au(Fmes)[C(NHMe)(NHPy-4)]] show that the presence of the NHPy-4 moiety formed induces the formation of supramolecular macrocycles only supported by hydrogen bond interactions, either with N-H groups of other molecules (tetrameric macrocycles), or with water molecules (dimeric macrocycles). Dimeric gold(I) carbenes were also produced using a diamine to form a bridging carbene, or using octafluorobiphenyl to form a Au-C6F4-C6F4-Au bridge, but the solid state structures of these dimers could not be solved. Most of the complexes herein described display luminescent properties.