Cyclophane-Type Macrocycles

The complexation of various molecular anions by other types of macrocyclic ligands has been reported [3.1-3.4] in particular with cyclophane-type compounds. Two such receptors are represented by the protonated forms of the macropolycycles 40 [3.29] and 41 [3.30]. Quaternary polybipyridinium compounds also bind anionic substrates [3.31]. Progress is also being made towards the developments of neutral anion receptor molecules [3.32]. The thermodynamic and kinetic data for anion complexation by macrocyclic receptors have been reviewed [2.18c]. 

Very recently, nice recognition of free and AT-acetylated amino acids (Gly, Ala, Phe) and some structurally related guests by a dicationic cyclophane-type A/,Ar -dibenzylated chiral derivative (4) of a bisisoquinoline alkaloid S,S-(+)-tetrandine (3 DBT) has been studied by NMR titration in water [31]. In contrast to other macrocyclic hosts, DBT shows high affinity and large enan-tioselectivity (K(S)/K(R)> 10) toward the smaller N-acetylalanine and binds the larger phenylalanine more weakly and nonselectively. The binding specificity of DBT was rationalized on the basis of molecular mechanics calculations. 

Schwabacher et al. (1972) prepared a cyclophane-type structure with metal ions coordinated into the walls of the macrocycle (70). This system was first reported in 1992 and shown to transport neutral aromatic hydrocarbons through an aqueous membrane. Even though this receptor has a net anionic charge, it has been illustrated to bind indole and naphthalene units functionalized with... 

In the framework of studies on macroheterocyclic ring systems of the cyclophane type, Stetter and Roos synthesized the macrocyclic tetraamines 32 and 33, which after recrystallization from dioxane or benzene retain solvent in stoichiometric amounts in the solid state. Particularly, 33 binds dioxane so strongly that even in vacuo during 30 hours at 150 °C it cannot be removed. 

Bisbenzylisoquinoline alkaloids form a large group (>150) of naturally occurring compounds in which two benzylisoquinoline moieties are joined by up to three ether links. Many of them have macrocyclic cyclophane-type structures, which makes them potentially capable of forming inclusion compounds with small guests. In addition, they have several stereogenic centers and may be useful... 

Diederich, F. and Dick, K. (1984) A New Water-Soluble Macrocyclic Host of the Cyclophane Type Host-Guest Complexation with Aromatic Guests in Aqueous Solutitm and Acceleration of the Transport of Arenes Through an Aqueous ase , J. Am. C hem. Soc. 106, 8024-8036. 

Macrocycles containing isoxazoline or isoxazole ring systems, potential receptors in host—guest chemistry, have been prepared by multiple (double, triple or quadruple) 1,3-dipolar cycloadditions of nitrile oxides, (prepared in situ from hydroxamoyl chlorides) to bifunctional calixarenes, ethylene glycols, or silanes containing unsaturated ester or alkene moieties (453). This one-pot synthetic method has been readily extended to the preparation of different types of macrocycles such as cyclophanes, bis-calix[4]arenes and sila-macrocycles. The ring size of macrocycles can be controlled by appropriate choices of the nitrile oxide precursors and the bifunctional dipolarophiles. Multiple cycloadditive macrocy-clization is a potentially useful method for the synthesis of macrocycles. 

The properties of natural macrocycles, the cyclodextrins, has stimulated interest in the preparation of synthetic macrocycles. Three basic types have been made macrocyclic amines, cyclophanes, and cyclic peptides. Hersh-field and Bender (33) prepared a bicyclic amine with hydroxamate sub-... 

In order to construct a hydrophobic three-dimensional cavity that is in-tramolecularly limited in space, we have prepared cage-type cyclophanes by linking macrocyclic rings. First we prepared a macropolycyclic host, which is constructed with two rigid macrocyclic skeletons of different size, tetraaza[3.3.3.3]paracyclophane as the larger one and tetraazacyclotetradecane as the smaller one, and four flexible hydrocarbon chains that connect the two macrocycles [40]. The flexibility of four hydrocarbon chains connecting the two macrocycles allows the induced-fit host-guest interaction in aqueous media. 

Controlled rotation of the molecular rings has also been achieved in catenanes composed of three interlocked macrocycles. For example, catenane 42H26+ (Fig. 13.37) is made up of two identical macrocycles 2 interlocked with a cyclophane containing two bipyridinium and two ammonium units.44 Because of the type of the macrocycles used, the stable coconformation of 42H26+ is that in which the two rings surround the bipyridinium units (Fig. 13.37a, state 0). Upon addition of one electron in each of the bipyridinium units, the two macrocycles move on the ammonium stations (Fig. 13.37b, state 1) and move back to the original position when the bipyridinium units are reoxidized. 

Most of the reported polyrotaxanes are based on CD and crown ethers. Only a few polyrotaxanes are from other macrocycles, e.g. phenanthroline-based cyclics and bisparaquat cyclophane. Most CD-based polyrotaxanes were prepared by threading CD on to preformed polymers because CD are only soluble in polar solvents or water and not compatible with typical polymerization conditions. On the other hand, aliphatic crown ethers are soluble in water and most organic solvents. Therefore, they have broadened the scope of polyrotaxanes in terms of both polymerization conditions and types of backbones. They have often been threaded onto polymeric backbones by using them as solvents during polymerizations. 

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