Macrobicyclic amides

Both the side chain of the amino acid pendant substituents and the substituents at the aromatic tripodal fragment are reported in [125] to affect chloride binding ability of the macrobicyclic amide ligands 164-166 obtained in [125] by Scheme 2.109. The covalent capsules having the 1,3,5-benzene moieties showed low affinity to chloride anion, whereas those with triple methyl-and ethyl-substituted benzene panels displayed stronger binding by one order of magnitude [125]. 

The in-out bicyclic amines prepared by Simmons and Park bear a remarkable semblance to the cryptands but lack the binding sites in the bridges. As a result, these molecules interact with electrophiles in a fashion similar to other tertiary amines and generally do not exhibit strong interactions with alkali or alkaline earth metal ions. The in-out bicyclic amines are prepared by reaction of the appropriate acid chlorides and amines in two stages to yield the macrobicyclic amine after reduction of the amidic linkages. A typical amine is shown above as compound 18. 

Amides, macrobicyclic, reduction of, 54, 89 Amine oxides, anhydrous, 50,... 

The bicyclization step is accomplished under identical conditions to the first macrocyclization step, the base being in this case added triethylamine. The reduction of the bicyclic amide 6 has to be realized with diborane (LiAlH4 cleaves the macrobicyclic system). Note that there is no need to isolate the intermediate aminoborane 7 the crude mixture obtained after... 

For synthetic purposes, the idealized macrobicyclic structure in Figure 1 can be viewed as a capped tripod. We have explored a new binding subunit for this work, 2,3-dihydroxyterephthalamide. A highly successful example of this approach is shown in Figure 2, where an essentially one-step synthesis gives a 50% isolated yield of the macfocycle formed from six amide linkages. 

Macrocyclic polyethers (or crown ethers) also possess attractive cation complexing abilities resulting in the formation of lipophilic species. Not surprisingly, such ionophores have been studied with respect to calcium sensors (32-34), and two examples are shown in Table 3.12. The macrobicyclic polyether-amide (7) provides a better calcium ISE than its monocyclic analogue (8). 

The synthesis of ligands bearing mixed type of chelating groiq)s such as amide-bipyridine or amide-phenantroline (e.g. 8) or having a macrobicyclic structures such as 9, allows a good compromise between stability and liuninescence properties of the corresponding complexes with lanthanide ions. 

A hexaamide covalent capsule 148 with an extended macrobicyclic framework has been described in [111] as a first polynucleating amide caging ligand with two of three pyridine-containing ribbed fragments having the same orientation and the third one looking at the... 

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