Linked macrocyclic ring systems

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... 

Vancomycin (Section 16.1.7) represents a major part of the presentation of Section 16. Vancomycin is a heptapeptide-like structure with interlocking macrocyclic ring systems linked to a disaccharide. Three representative syntheses of vancomycin aglycon are presented. They include a most impressive total synthesis from the Evans Group (Section 16.1.7.1), 37,38 the Nicolaou Group (Section 16.1.7.2), 39 and the Boger Group (Section 16.1.3). 40 Finally, the chapter is concluded with the Nicolaou total synthesis of vancomycin. 41 ... 

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. 

Despite the overall decline in output, the year has produced ftirther interesting developments in the fteld of hypervalent phosphorus chemistry. These include phosphoranes containing acetylenic links, the synthesis and enantiomeric separation of a bicyclic phosphorane with chirality only at phosphorus, and a wide range of phosphoranes incorporated within macrocyclic ring systems (Houlla et al). In addition Lattman has reported on phosphoranes bound to transition metals or enclosed within calixarene skeletons and Holmes and his co-workers have made further substantial contributions on the X-ray crystal structures of phosphoranes containing eight-membered rings. 

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-... 

Several macrocyclic ligands are shown in Figure 2. The porphyrin and corrin ring systems are well known, the latter for the cobalt-containing vitamin Bi2 coenzymes. Of more recent interest are the hydroporphyrins. Siroheme (an isobacteriochlorin) is the prosthetic group of the sulfite and nitrite reductases which catalyze the six-electron reductions of sulfite and nitrite to H2S and NH3 respectively. The demetallated form of siroheme, sirohydrochlorin, is an intermediate in the biosynthesis of vitamin Bi2, and so links the porphyrin and corrin macrocycles. Factor 430 is a tetrahydroporphyrin, and as its nickel complex is the prosthetic group of methyl coenzyme M reductase. F430 shows structural similarities to both siroheme and corrin. 

The metal ion chemistry of such linked bis-ring macrocycles has been extensively reviewed over recent years [2-6], In view of this, the present discussion is restricted to linked tii- and higher-ring 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. 

From a structural standpoint, these compounds consist of a trichothecane sesquiterpene diol linked through ester bonds to a diacid derived from esterification of the ( )-acid of a (Z, )-muconic acid with a 5-hydroxypentanoic acid segment (containing various substitution patterns). As the synthesis of the sesquiterpene diol unit is beyond the scope of this chapter, we have limited discussion to the methods employed for formation of the macrocyclic ring of these substances. Papers concerning the construction of the various trichothecane diol systems may be found by consulting the references cited in this section. 

Synthesized (Fig. 28) in 32% yield [51,52] starting from 1,5-dihydroxy-naphthalene, the macrocyclic polyether 20 contains a 1,5-dioxynaphthalene unit and a bis(methanol)TTF ring system, linked in a cyclic fashion by two tetraethylene glycol chains. When this macrocyclic polyether was reacted with the precursors to CBPQT4+, the resulting [2]catenane 214+ was formed in 23% yield. 

Structurally, 218 and 219 feature a heptacycUc ring system, containing a twisted 16-membered macrocycle, a hindered quaternary center linking two tryptophan residues and a strained ot-carboline. Recently, Baran and coworkers reported the first synthesis of kapakahines B and F by a diastereoselective, oxidative N-C bond formation and a late-stage shift of structural topology [89]. 

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