Macrocycles Other than Crown Ethers

Macrocycles Other than Crown Ethers Systems containing Nitrogen as the only Heteroatom. - The aza[18]annulene (35) has been synthesized by photolysis of (36) at — 80°C. Aza[14]-annulenes have been prepared by the same route. An efficient route to... 

Related to the crown ethers are compounds, such as hexamethyl-[14]-4,ll-diene (6), which differ by the replacement of one or more of the oxygen atoms by other kinds of donor atoms, particularly N or S. MacrocycHc amine and thioether compounds have been synthesized. Compounds having more than one kind of heteroatom in the ring are called mixed-donor macrocycles. The naturally occurring metaboUtes nonactin [6833-84-7] and monactin [7182-54-9] have both ether and ester groups incorporated in the macrocyclic stmcture. 

Further comments. The preceding discussion outlines typical syntheses for simple polyether crown rings. It needs to be noted that a considerable number of other types of crown derivatives, displaying a variety of molecular architectures, has also been synthesized. Many of these types parallel the structurally developed macrocycles (which incorporate mainly donor atom types other than ether oxygen) discussed in Chapter... 

It should be stressed that there is not alwaysjustice in reseach evaluation. The selective formation of inclusion complexes by cyclodextrins (such as 11) was established by Cramer [6] at least 15 years earlier than that by crown ethers. However, cyclodextrin studies forming an independent branch of host-guest chemistry seem underestimated in spite of their considerably greater practical importance at present than that of other host macrocycles (crown ethers 17, calixarenes 18, etc.). Sometimes they are even totally neglected by discussing inclusion phenomena [7]. 

Polyoxa macrocycles, known more commonly as the crown ethers, comprise an extensive area of research, with a repertoire of types and variations. Some of these macrocycles have been utilized predominantly for purposes other than metal ion complexation, and these will not be discussed in depth in this review. Included in this latter category are the polycarbonyls, polylactones,polylactams and carcerands. " ... 

Casnati and co-workers have devised a calixarene crown ether (7.17) that shows a preference for potassium over sodium of 22,000.85 A macrocyclic polyether with attached 8-hydroxyquinoline groups (7.18) favors barium over other alkaline earth cations by a factor of more than 10 million.86 Compound (7.19) shows a preference of magnesium over calcium of 590.87 Compound (7.20) has the highest known binding constant for Ag(I), log K 19.6.88... 

There have only been a few preclinical studies using the aza-crown macrocycles. The toxicity of the crowns has been somewhat studied. Crown ethers are more toxic than the aza-crown macrocycles because toxicity arises from the slow leakage of potassium ions out of and sodium ions into cells (Gokel, 1991). Dibenzo-18-crown-6 is much less toxic than the other crown ethers because it is much less soluble in water. Complexed ligands are much less toxic than the uncomplexed ligand. For example, complexes of [12]N4-tetraacetate are not toxic while the uncomplexed ligand will remove metal ions from cells (Lauffer, 1987). Thus, it is important to have stable complexes when the macrocycles are used for medicinal purposes. 

Crown Ethers, Crown compounds. Macrocyclic polyethers with the repeating unit (-CH,-CH2-0-), where n is greater than 2. Crown compounds with other heteroatoms (N, S, P) are known. Prepd by C. J. Pedersen,... 

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