Macrocyclic torands

Macrocyclic torands (telomestatin and derivatives) as natural products of Streptomyces anulatus emerge as agents targeting the G-quadruplexes such a hexazole-designated oxazole (HXDV) is inhibitory to human leukemia lymphoblasts [432]. Telomestatin derivatives of macrocyclic stmctures (with 6 oxazole rings) and porphyrin-based ligands stabilize telomerase-driven cell divisions [433 35], but so far have not reached the clinics. 

AC and AEC complexation is also effected efficiently by other macrocyclic ligands such as the spherands 13, cryptospherands 14 [2.9, 2.10], calixarenes [2.38, A.6, A.23], torands [2.39], etc., some of them, for instance the spherands displaying particularly high stabilities. A special case is represented by the endohedral complexes of fullerenes in which the cation (Sr2, Ba2+, lanthanides) is locked inside the closed carbon framework [2.40],... 

Numerous macrocyclic and macropolycyclic ligands featuring subheterocyclic rings such as pyridine, furan or thiophene have been investigated [2.70] among which one may, for instance, cite the cyclic hexapyridine torands (see 19) [2.39] and the cryptands containing pyridine, 2,2 -bipyridine (bipy), 9,10-phenanthroline (phen) etc. units [2.56,2.57,2.71-2.73]. The [Na+ c tris-bipy] cryptate 20 [2.71] and especially lanthanide complexes of the same class have been extensively studied [2.74, 2.75] (see also Sect. 8.2). 

The synthesis of the pyrrole-pyridine-containing expanded porphyrins 4.196 and 4.197 was reported by Bell, et al. in 1993. These macrocycles, termed torands because of their rigid torroidal structure, were prepared via an elaborate linear synthesis, part of which is shown in Scheme 4.6.4. The key macrocyclization step in the synthesis involves the pyrolysis of the bis(semicarbazone) 4.195 to afford torand 4.196 in up to 69% yield. This torand may then be dehydrogenated with... 

Polypyridine Torand 1. Complexes of alkali metal triflates and picrates have been prepared from the monotriflate salt of torand 1, which is isolated directly from the macrocyclization reaction mixture. As shown in Figure 3, neutralization of the triflate salt with alkali metal hydroxides or carbonates gives the alkali metal complexes. With triflate or picrate counterions, torand complexes and salts partition selectively into chlorofonn rather than water. Thus 1 can be shuttled back and forth between the triflate salt and various complexes simply by washing the chloroform solution with aqueous acid or base. The free ligand is prepared by reaction of the triflate salt with tetra-n-butylammonium hydroxide in butanol/acetonitrile. Combustion microanalysis showed that the Li, Na, K, Rb and Cs complexes all have 1 1 host/guest stiochiome-try, despite the cavity/ion size mismatch at both ends of the series. The X-ray crystal... 

The temi " torand," derived by combination of toms" and ligand, denotes a macrocyclic ligand in which the perimeter of the large ring is completely formed by fusion of smaller rings. Three kinds of torands are currently known, dodecahydrohexaazakekulene (1,/ =... 

A lengthy synthesis of the parent dodecahydrohexaaza-kekulene (1, r =R = H) was reported by Ransohoff and Staab. - The final, macrocyclization step apparently gave the torand in 3% yield as a sparingly soluble solid. 

Torands and closely related molecules, such as cycloar-enes, sexipyridines, and expanded heterohelicenes (molecular coils), still constitute a relatively small group of known compounds. The main reason for this is purely synthetic fusion of multiple rings requires many synthetic steps and low-yield macrocyclization reactions compound the problem. Clearly, better methods are needed for the synthesis of torands to enable more complete ex-... 

Bell, T.W. Tidswell, J. Torands. In Macrocycle Synthesis A Praetieal Approaeh Parker. D., Ed. Oxford University Press Oxford, 1996 119-143. 

ABSTRACT. A series of macrocyclic ligands related to hexaaza[is]-annulene form stable complexes with alkali metal and alkaline earth ions. A planar, substituent-solubilized "torand", consisting of multiply fused pyridine rings, has been synthesized and has been found to sequester calcium from a dilute source. 

Since the discovery of crown ethers by Pedersen there have been many attempts to design and synthesize hosts whose ion affinities and selectivities surpass those of the original cyclic polyethers. Particularly important examples are the cryptands and spherands. These polycyclic receptors form stronger complexes and are generally more selective than crown ethers, however their complexes equilibrate more slowly as a consequence of their more rigid, encapsulating structures. This report is focused on the development of a new class of macrocyclic hosts, the torands, whose rigid toroidal structures should permit rapid equilibration of complexes. 

The complementary segment, bis(3-dimethylaminoenone) 14 was also prepared from 9 via dibenzylidene derivative 13. Macrocyclization was effected by treating a 1 1 mixture of 12 and 14 with trifluoromethane-sulfonic acid in hot acetic acid followed by ammonium acetate. Neutralization of the reaction mixture with lithium hydroxide and chromatography of the chloroform extract gave torand 15 as the calcium triflate complex in 12 yield. Calcium is introduced as a 0.3% impurity in the triflic acid used in this experiment. The spectroscopic properties of 15 are similar to those reported for the unsubstituted parent system. 

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