Macrocyclic assemblies polyethers

Self-assembly of secondary dialkylammonium ions with macrocyclic polyethers and formation of pseudorotaxanes 96CC1483. 

Halichondrin B (204) Macrocyclic polyether Eribulin (E7389, NSC-707389) (205) Oncology Tubulin assembly inhibition Phase II/III (advanced or metastatic breast cancer) Eisai 937-943... 

Figure 14. The self-assembly of [2]pseudorotaxanes incorporating the bis(hexafluorophos-phate) salt 23-2PF6 and the macrocyclic dioxyarene-based polyethers 4 and 24-29.

The application of new bis-substituted dtc ligands containing various polyether and amide spacer groups has lead to the constmction of a wide range of metal-directed assembled bimetallic macrocycles and cryptands (Scheme 5).48 Cryptands can be assembled through careful choice of a suitable octahedral stereochemical directing metal centre such as iron(III) and cobalt(III). 

Binding of a complex anionic species with the help of hybrid macrocycles able to provide different interactions with the anion simultaneously was demonstrated in an elegant manner by Stoddart et al. They reported the organization of macrocyde via the anion-assisted assembly of large [5]- and [6]pseudorotaxanes from dibenzy-lammonium threads and polyether macrocydes. The resulting systems were found to be interwoven around a central hexafluorophosphate anion (Scheme 9.12, structure 59) [117]. 

Rotaxanes 145 <1993CC1269>, 146 <1993CC1274>, and 147 <1996JA4931> incorporating Jt-electron-deficient bipyridinium-based dumbbell components and one or more 7t-electron-rich hydroquinone-based (and/or dioxy-naphthalene-based <1995CC747>) macrocyclic polyether counterparts have been assembled and their spectroscopic and electrochemical properties investigated in connection with the potential fabrication of chemically, photochemi-cally, and electrochemically active molecular devices <1996JA4931>. 

The generality of this ordering process was established by the further syntheses of the [2]-pseudorotaxane shown in Figure 4.5 and the (then) novel [3]-pseudoro-taxane shown in Figure 4.62 The first of these species involves the 1 1 self-assembly of 14 with one molecule of the bis(paraquat- -phenylene) tetracationic macrocycle, while in the second species the polyether component is 15 and the corresponding ratio is 1 2. The successful construction of the latter species represented somewhat of a landmark in the use of self-assembly processes of the present type since it demonstrated the feasibility of extending the work to large synthetic... 

In an extension of the previous studies involving 13, it has been demonstrated that a number of other [2]-catenanes can be synthesised using self-assembly procedures in which the donor macrocyclic polyethers incorporate both hydroquinone and 1,5-dioxynaphthalene units, while the acceptor tetracationic cyclophanes contain bipyridinium and/or its extended analogue, bis(pyridinium)ethylene. Although the trans carbon-carbon double bond in the bis(pyridinium)ethylene units are... 

Aromatic templates, in conjunction with coordinative bonds, have been employed by Sanders et al. [42] to self-assemble a [2]catenane incorporating a chiral metallomacro-cycle. The 1,5-dioxynaphthalene-based macrocyclic polyether 60 threads onto the r-elec-tron-deficient compound 61 in MeCN. Thus, when both compounds and Zn(OS02CF3)2 are mixed in this solvent, threading of 60 onto 61 is followed by the [2 + 2] assembly of a helical metallomacrocycle as a result of the tetrahedral coordination of two Zn centers by the bipyridine ligands appended to the r-electron-deficient recognition sites. The resulting [2]catenane 62 was characterized by a combination of H-NMR spectroscopy and electrospray mass spectrometry. 

A few macrocyclic polyethers containing a ring phosphorus atom are known. As a rule, the synthesis of such substances is not carried out by template processes. However, the assembly of crown ethers possessing ring phosphonyl groups has been achieved on alkali metal ion (lithium, sodium, potassium) matrices [181-184]. The product LI546 is synthesised in an inert atmosphere (Eq. 6.66). 

There are two ways of varying the assembly of monomeric and dimeric macrocycles, by using a suitable template and by selection of solvent. Reaction in polar solvents favours production of 28-membered compounds, whereas in solvents of relatively low dielectric constant 14-membered compounds are favoured. Yields of polyethers are influenced to a greater extent by the template effect than by the solvent natme [184]. 

Recently, a third process has been identified which constitutes an example of strict self-assembly.The so-called slippage approach to rotaxane synthesis Figure 5) is based upon size complementarity between the macrocyclic polyether, BPP34C10, containing two 7i-electron rich recognition sites and the stoppers comprised of suitable tetra-arylmethane groups at the ends of dumbbell-shaped molecules incorporating at least one 4,4 -bipyridinium unit. ... 

Before the advent of slippage, the formation of [2]rotaxanes included a very limited array of choices for the macrocyclic bead and the rod. In essence, the use of macrocyclic polyethers, like BPP34C10 as the bead component, is only beneficial if there is a mutual recognition between the 7C-electron rich hydroquinol rings contained within the crown and a 7i-electron poor site on the dumbbell component. This route was limiting in that it requires two 4,4-bipyridinium dications to be present in order that one BPP34C10 ring can be incorporated into the assembly Scheme 10). 

It is obvious that we can only self-assemble [3]catenanes if we increase the size of both the neutral and tetracationic components. So far, the use of TPP68C20 and the large cyclophane [BBIPYBIBTCY]4+ has met with no success. We attribute this lack of catenation to the large dimensions of the two components, and, in the case of TPP68C20, to its flexibility. The macrocyclic polyether TPP51C15 Scheme 21),... 

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