Macrocycle structural investigation

The important difference between linear and cyclic peptides is the reduced conformational flexibility imposed by the cyclization. 14,151 Cyclic peptides have, therefore, been under intense investigation with respect to their conformational preferences 30,31 and their different turn motifs, e.g. reverse turns. 32 35 To differentiate between the structural influences of the numerous sequence elements the following special concepts have been described 161 (1) Global constraints are structural characteristics that restrict the whole molecule, e.g. the macrocyclic structure of the peptide framework and (2) local constraints comprise a large number of structure-inducing building blocks, such as proline, D-amino acids, and turn mimetics. 

The reaction of ferrocenecarbaldehyde (98) and resorcinol (99) under acidic conditions gave the phenolic macrocycle (100), which on addition of chlorobromomethane in the presence of a base produced the first redox-active cavitand (141,142) (101) (Scheme 31). An X-ray structural investigation on crystals of (101), obtained from a dichlorometh-ane-diethyl ether solvent mixture, revealed the inclusion of a dichloro-methane guest molecule within the cavitand host cavity (Fig. 23). Related redox-active cavitand host molecules ((102) and (103)) containing ferrocene moieties lining the wall of the cavitand cavity have also been prepared by our group (141, 142). 

The theoretical analysis of XANES by DV-Xa method has also been reported to be very useful for the structural investigation as well as study of chemical state and chemical bonding for the square-planar tetraaza and diazadioxa macrocyclic copper(II) complexes. ... 

An interesting synthetic and structural investigation deals with the chiral configuration of cyclotriphosphazenes carrying macrocyclic substituents. Two configurations of compound (83) could be isolated from a reaction mixture of (82) and piperazine, viz. a meso- and racemate-form as proven by X-ray analysis. Further aminolysis yielded two meso-forms of (84), one with a plane of symmetry, the other with a center of symmetry. The results are consistent with inversion of configuration at a P(OR)Cl center for each substitution step going from (82) to (84). The patterns of the P NMR spectra are consistent with the X-ray structures. ... 

Structural investigation into the steric control of polyether complexation in the lanthanide series - macrocyclic 18-crown-6 versus acyclic pentaethylene glycol, R. D. Rogers, A. N. Rollins, R. D. Etzenhouser, E. J. Voss and C. B. Bauer, Inorg. Chem., 1993, 32, 3451. 

Early work involved the use of metal cations as templates in macrocyclization reactions. Seidel [6] reacted 2-aminobenzaldehyde 1 with anhydrous zinc chloride (Scheme 1-1), but did not recognize that he had prepared the macrocycle 2, and it was not until 40 years later that Busch [7] and co-workers elucidated the structure of this type of macrocycle and investigated how metal cations template its formation. 

Due to the critical nature of the cyclization step for the synthesis of macrocyclic structures, a number of efforts have been devoted to attempting to better understand and define this process. Initial studies focused on the factors involved in the formation of cyclic peptides." These investigations revealed the positive effects of preorganization of cyclization precursors on the reaction rate and yield. They also showed the benefits of mixed absolute configurations," N-methylation and other conformational constraints on cyclization. 

Ovchinnikov, Ivanov and Shkrab have drawn an analogy between the complexation of an alkali-metal cation with a macrocyclic ligand and the alteration of the solvation shell of a cation upon replacement of one solvent by a second solvent of greater solvating ability. The analogy was based on data 9 from a large number of X-ray structural investigations of complexes of... 

Macrocyclic polyamines may be viewed as an extended form of linear polyamines 13-161 with one less degree of saturation. Polyamines with lower degrees of saturation, have important biological functions. Compounds such as macrocyclic polyimines 171 and porphyrines 18), function as 02 carriers and activators, promote photosynthesis, form the basic structure of vitamine B12, etc., and for these reasons have been subjects of intense investigation. 

According to Hiiekel s rule, turcasarin should not be aromatic, but even if the macrocycle should fulfill the (4n +2) rule for aromatic systems the lack of planarity due to the loop conformation would prevent aromatic stabilization. In fact, the existence of the loop conformation in which the whole macrocycle is twisted was demonstrated by X-ray structure analysis and NMR investigations. 

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