Hybrid macrocyclic

Total synthesis of complex (macrocyclic) natural products using fast and flexible strategies and diversity-oriented synthesis of natural product-like macrocycles are important research topics in our laboratory. The following sections describe the total synthesis of epothilone D and epothilone D5 analogues, DOS of cyclopeptide alkaloid analogues, of biaryl ether macrocycles, and of steroid/peptide hybrid macrocycles, respectively. 

The synthesis of a small library of very large (up to 60-membered) steroid/ peptide hybrid macrocycles has been achieved using double and fourfold Ugi reactions. This type of compound has not previously been described in literature. Neither have multicomponent reactions been used so far to form directly macrocycles of this size. In fact, synthetic macrocycles of this size with this structural complexity are very rare. 

Sessler, J.L., Zimmerman, R.S., Bucher, C., Krai, V. and Andrioletti, B. (2001) Calixphyrins. Hybrid macrocycles at the structural crossroads between porphyrins and calixpyrroles, Pure Appl. Chem. 73, 1041-1057. 

Binding of a complex anionic species with the help of hybrid macrocycles able to provide different interactions with the anion simultaneously was demonstrated in an elegant manner by Stoddart et al. They reported the organization of macrocyde via the anion-assisted assembly of large [5]- and [6]pseudorotaxanes from dibenzy-lammonium threads and polyether macrocydes. The resulting systems were found to be interwoven around a central hexafluorophosphate anion (Scheme 9.12, structure 59) [117]. 

With precursors in hand and reactions all worked out for the construction of both pericyclynes and exploded pericyclynes, the temptation to prepare hybrid macrocycles containing simple alkynes along some of the edges and 1,3-diynes along the others eventually became irresistible. Fig. 9-19 shows the route to one such crossbreed, 68, a 23-membered ring with nine triple bonds (cf. Fig. 9-13) [22, 31]. 

Density functional theory is a successful approach for the description of ground-state properties of metals, semiconductors, and insulators. It also has become an attractive method to calculate complex materials, such as proteins and carbon nanotubes. For example, DFT calculation has been used to compute anion-binding properties of 2,6-diamidopyridine dipyrromethane hybrid macrocycles (18), to predict drug resistance of HIV-1 reverse transcriptase to nevirapine through point mutations (19), and to analyze the 32-adrenergic G protein-coupled receptor (20). A free DFT software program also is available... 

Sessler JL. Katayev E. Pantos GD. et al. Fine-tuning the anion-binding properties of 2.6-diamidopyridine dipyrromethane hybrid macrocycles. J Am Chem Soc 2005 127 11442-11446. 

Recently Katayev, Sessler and co-workers have further developed the hybrid macrocycle systems by replacing the pyridine-2,6-dicarboxamide moieties used in receptors 43 and 44 with bipyrrole and dipyrromethane subunits... 

Katayev and Sessler have further investigated the anion complexation behavior of the amido-imine-based hybrid-macrocycles L32, L33, and L34 that are effective anion receptors (in the form of their telrabutylanunonium salts) for anions such as Cl , Br , CH3COO , HS04, H2P04, ... 

There are a number of methods for the synthesis of quinoxaline macrocycles that have been successfully implemented for constructing quinoxahnoporphyrins, quinoxalinoporphyrazines, quinoxalinocrown ethers, quinoxalinocavitands, quinoxalinohemispherands, and hybrid macrocycles. In these macrocyclic systems, quinoxaline moiety(ies) were attached to the macrocyclic skeleton by the atoms N(l) and C(3), N(l) and N(4), C(2) and C(3), C(2) and C(8), C(6) and C(7). In these cases, macrocyclic systems in which the quinoxaline moiety is fixed in a macrocyclic skeleton by atoms of C(2) and C(3) are represented best of all. Considerably less attention is paid to their 6, 7 analogs, and all the others are represented in single works. 

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