Macrocyclic synthetic models

Katayev EA, Sessler JL, Khrustalev VN et al (2007) Synthetic model of the phosphate binding protein solid-state structure and solution-phase anion binding properties of a large oligopyr-rolic macrocycle. J Org Chem 72 7244—7252... 

The absolute configurations at C-7, C-8, and C-10 were elucidated to be S, S, and 5, respectively, by comparison of the NMR data of C-l-C-12 segments with those of synthetic model compounds for the tetrahydrofuran portion. The structure of amphidinolide T1 (19a) has been confirmed by a single crystal X-ray analysis.Amphidinolide T1 (19a) possesses an odd-numbered macrocyclic lactone ring but has no vicinally located one-carhon branches. 

The terminal step in methane generation by several methanogenic organisms, of which the best studied is the archaeon Methanobacterium thermoautotrophicum, is catalyzed by the enzyme S-methyl coenzyme M reductase (methylreductase, EC 1.8.-.-). This enzyme contains a macrocyclic tetrapyrrole-derived cofactor, F430, at the active site coordinating Ni(II) in the resting state. A Ni(I) state (Ni1F430) has been proposed as the active form of the cofactor. Extensive mechanistic and spectroscopic studies have been performed on the holoenzyme, isolated cofactor, and various synthetic model compounds. These studies are summarized in... 

In the antigen active fragments of antibodies (Fab), in synthetic model peptides, and in planar macrocyclic lactams, proteins provide specific recognition sites for all kinds of ions, small molecules, and polymers. 

The ability of valinomycin and of macrotetrolides to increase the potassium permeability of biological membranes was interpreted from the viewpoint that these substances act as carriers. Because of the great complexity of biological membranes, however, detailed information on the transport mechanism could not be obtained from these experiments. For this reason, artificial or synthetic model membranes are now used in many studies, with macrocyclic antibiotics or with other synthetic carriers. 

The intramolecular version for synthesizing cyclic and polycyclic compounds offers a powerful synthetic method for naturally occurring macrocyclic and polycyclic compounds, and novel total syntheses of many naturally occurring complex molecules have been achieved by synthetic designs based on this methodology. Cyclization by the coupling of an enone and alkenyl iodide has been applied to the synthesis of a model compound of l6-membered car-bomycin B 162 in 55% yield. A stoichiometric amount of the catalyst was used because the reaction was carried out under high dilution conditions[132]. 

Ochrymowycz and his coworkers have also prepared a number of polysulfur macrocycles for use in biological or biological model systems . The synthetic methodology is essentially similar to that described above except that certain of the sulfur containing fragments were prepared by addition reactions to ethylene. Two examples of this approach, taken from ref. 59, are shown in Eq. (6.9). 

The following is a comprehensive smwey of the chemistry of macrocycles comprised entirely of phenyl and acetylenic moieties. Although over fom" decades old, this area of research has come into its own just in the last few years. Widespread interest in the field has been spurred by recent discoveries utilizing these compoimds as ligands for organometallic chemistry, hosts for binding guest molecules, models of synthetic carbon allotropes, and precursors to fullerenes and other carbon-rich materials. This review will discuss the preparation of a tremendous variety of novel structm-es and detail the development of versatile synthetic methods for macro cycle construction. 

Recently reported synthetic macrocyclic molecules with hydrophilic cavities containing multiple binding atoms and with hydrophobic exteriors make possible controlled studies of selective cation complexa-tion. Certain of these cation-ligand systems appear to mimic biological systems which have remarkable element specificities. Such cation-ligand systems may be considered as models for the study of this unusual property of living systems. 

We have already reported that synthetic peptide lipids, having ot-amino acid residuefs) interposed between a polar head moiety and a hydrophobic doublechain segment, can be used as models for functional simulation of biomembranes [23]. On this ground, we are to clarify molecular recognition specificity by supramolecular assemblies formed in combination of the macrocyclic receptors with the peptide lipid as artificial cell-surface receptors. 

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