The natural macrocycles

In this chapter, representatives of the natural macrocycles are presented and selected model studies are also described. Emphasis will be given in the following discussion to a few of the better understood areas involving natural macrocyclic systems. Initially, the nature and function of the cyclic antibiotic category of macrocycles are discussed. Subsequently, aspects of the roles of the natural N4-donor systems are presented. 

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Many other cyclic and noncyclic organic carriers with remarkable ion selectivities have been used successfiilly as active hosts of various liquid membrane electrodes. These include the 14-crown-4-ether for lithium (30) 16-crown-5 derivatives for sodium bis-benzo-18-crown-6 ether for cesium the ionophore ETH 1001 [(R,R)-AA -bisd l-ethoxycarbonyl)undecyl-A,yVl-4,5-tctramcthyl-3,6-dioxaoctancdiamide] for calcium the natural macrocyclics nonactin and monensin for ammonia and sodium (31), respectively the ionophore ETH 1117 for magnesium calixarene derivatives for sodium (32) and macrocyclic thioethers for mercury and silver (33). 

Cyclohexadecen-l-one can be added to perfume compositions as a substitute for the natural macrocyclic ketone musks. 

A close relationship has existed between the field of bioinorganic chemistry and that of macrocyclic or macropolycyclic chemistry for the last 20 years. In part, this is due to direct overlap relating to the existence of the natural macrocyclic antibiotics and porphyrins. However, a long and fruitful association also exists in a third area the use of macrocyclic or cryptate complexes to model metalloprotein active sites or to mimic their chemistry (1-3). 

For example, potassium-selective electrodes can be constructed with the natural macrocycle valinomycin as a neutral carrier in diphenyl ether. This membrane has a much... 

One also has to consider that not aU amino add-based natural ligands are structurally so complex as a protein. There are a number of relatively low-molecular-weight natural peptides, for example, cyclopeptides, that very efQciendy and selectively interact with a complementary substrate. Notable examples are the antibiotics vaUnomycin, 1, and vancomycin, 2, as weU as the natural macrocyclic ligand patellamide A, 3 (Scheme 1). 

Fig. 3 Three-dimensional representation of the natural macrocyclic glycopeptides chiral selectors whose physicochemical properties are hsted in Table 1. The color code is given in Fig. 2 caption...

The outstanding challenge in this area is the synthesis of the natural macrocyclic diester alkaloids. A first step in this direction was taken by Robins and Sakdarat 251), when they managed to reconstruct an 11-membered macrocyclic diester (85) from (+)-retronecine and 3,3-dimethyl-glutaric anhydride. The mixture of 7- and 9-monoesters of retronecine initially produced was cyclised intramolecularly via the corresponding 2-pyridinethiol esters. 

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