Macrocyclic polylactones, polylactams and related compounds

A unique approach to the controlled design of such systems as macrocyclic polylactones, polylactams and related compounds has been developed [1]. The synthesis of these substances, called biomimetic macrocyclic molecules by reason of their resemblance to naturally occuring ionophores (such as valinomycin, nonacdn, enniatin and enterobactin [2-5]), is carried out by a covalent-template method. This description arises from the use of elements forming covalent bonds (tin, silicon, antimony, boron) as matrices. 

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. 

The tin-containing compounds involved in the above processes exercise their template function by controlling the conversion of non-cyclic diols to cyclic stan-noxanes. This activates the corresponding oxygen atoms, thus facilitating interaction of diacyl dihalides with the latter, to give macrocyclic tetralactones as the only 

X-Ray studies of L1562, L1563 and L1566 verifying the formation of the respective tetralactones have been performed [10]. 

It is supposed [15] that the reaction proceeds stepwise via formation of a 1 1 open-chain intermediate (Eq. 7.5). 

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The production of new macrocyclic systems has become possible due mainly to the development of new template centres for specific ligand products, such as the covalent-template approach to the synthesis of macrocyclic polylactones, polylactams and related compounds. Also of note is the the assembly of the cat-echoylamide systems H6L1019 and H6L1022 on an iron(III). In these situations the specific arrangement of functional groups required for macrocyclisation is a result of complex formation. 

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