Linked macrocyclic systems

A range of three-ring, linked aza macrocycles incorporating 9-membered 1,4,7-triazacyclononane (tacn), 12-membered cyclen and 14-membered cyclam and its derivatives have been reported but the number is much less than for the corresponding systems incorporating two linked macrocycles systems containing four or more linked rings are quite rare. 

Although 1,4,7-triazacyclononane was first incorporated into linked macrocyclic systems around three decades ago [7], it was only in 1997 that the corresponding three-ring analogue 1 was synthesised and investigated. The synthesis of 1 [8] (Scheme 1) proceeds from the tricyclic orthoamide derivative of 1,4,7-triazacyclononane 2 [9] and involves reaction with l,3,5-tris(bromomethyl)benzene in acetonitrile in a 3 1 molar ratio followed by base hydrolytic work-up of the product. The addition of excess HBr to the reaction mixture led to isolation of 1 as its nonahydrobromide salt in 76% yield. 

Two or more macrocyclic entities can be linked in several different ways, as shown by (144) and (145).241 Linked macrocyclic systems can bind simultaneously two or more metal ions, giving rise to complexes with unusual electronic, catalytic, and/or redox properties.242 Macrocycles incorporating phenanthroline moieties (146) are useful sensing agents for ion-selective electrodes and fluorimetry, and suitable carriers for selective ion transport in liquid-membrane systems.243,244... 

Linkage isomerizations, osmium, 37 335-339 Linked cubane clusters, Fe—S proteins, biological implications, 38 55-56 Linked macrocyclic ring systems, 45 75 dinuclear systems, 45 89-95 triaza ring systems, 45 76-87 Li—N—Li linkages, 37 100-101 Lipoxygenase, inhibitors, 36 41 Liquid-liquid extraction of metal ions, 9 1-80 with acidic P-based extractants, 9 34-48 with acidic P-based extractants dinuclear, 9 47-48 mononuclear, 9 34-47 with amines and amine oxides, 9 49-56 complexes in, 9 68-71 countercurrent extraction method, 9 15-25... 

In the bisbenzylisoquinolines the size of the macrocyclic system affects the chemical shifts of some groupings of protons in a characteristic way. In certain conformations of the 21-membered ring in 5-7 ether linked systems the 2- and 6-substituents lie over aryl rings with a consequent shift to lower frequency. This is illustrated by the H NMR spectrum of thalictine [39] (38) which shows absorption for the 8-and 8 -protons to low frequency of the other aromatic protons. 

In this article the design, synthesis and d-block metal ion chemistry of some more recent examples of covalently-linked, macrocyclic ligand systems are discussed. The use of macrocyclic rings in such systems is not surprising given that the resulting macrocyclic complexes often exhibit both enhanced kinetic and thermodynamic stabilities and hence tend to retain their integrity under a variety of conditions - a lesson that nature knows well. 

A considerable number of linked tetraaza macrocyclic systems have now been reported. An early example, first isolated in low yield as its... 

Synthetic methods for the preparation of azacycloalkanes and -cyclophanes also include modification of a preformed macrocycle. This is commonly performed by means of conventional functionalization reactions which do not follow particular strategies and are adequately described in the cited literature. Conversely, a large strategic effort has been dedicated to the preparation of topologically constrained ligands and linked-ring systems. The... 

The technique is applied to link non-cyclic ligsons together to form macrocyclic systems. The ligson heteroatoms have weak donor properties, so that centres such as transition and rare earth element, alkali, and alkaline metal ions are not able to play a template role in synthesis from the relevant species. The metalloids are able to form covalent bonds to weak donors and are thus suitable for the realisation of the required reactions. Organo-element compounds of appropriate metals are used for covalent-template synthesis. These combine the coordination ability of metals and the substitution ability of organic moieties, and therefore facilitate the wide range of chemical conversions involved in template processes. The basic feature of the reactions considered here is the weakness of bonds between matrix and ligsons, so that the synthesis of the free macrocyclic compound may be completed by release of the template. 

Acetylenes are often found as components of synthesized macrocyclic systems, chiefly as a result of the ease of linking two C=C units by methods referred to earlier. Among annulenes which have been prepared by this method are (33), (34), and (35), the lattercontainingthesubstituentR within the cavity of the r-electron cloud. Annulenones, e.. (36), (37), and (38),... 

FIGURE 27.2 (a) Arene-coupled macrocyclic systems incorporating meto-carboranes, (b) Cyclooctaphane assembling ortho- and meto-carborane units, and (c) xylyl-linked tetramer. 

Roseophilin (273), a deeply red-colored pentacyclic compound isolated from the culture broth of Streptomyces griseoviridis, is a novel antitumor antibiotic. Compound 273 possesses a topologically unique pentacyclic skeleton, consisting of a 13-membered macrocycle incorporated in an ansa-bridged azafulvene, which in turn is linked to a conjugated heterocyclic ring system. The absolute stereochemistry of roseophilin, as depicted in Fig. 9, was unknown until the first total synthesis published by Tius and Harrington in 2001 [125]. All syn-... 

Using similar methodology, macrocycle 126 was prepared, as well as the unusual monoene 127 [76]. Considerable debate in the literature over the last thirty years has focused on whether dehydrobenzoannulenes are able to sustain induced ring currents [5al. Although fusion of arenes to the annulenic core provides rigidity and stability, this also weakens the diatropicity/paratropicity of the macrocycle significantly. Until quite recently, the number of planar systems available for study was limited however, with the the addition of 123 and 126, the series of alkyne-linked, tribenzo-fused dehydroannulenes is complete from... 

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