Seven-membered ring heterocycles

Nitrobenzoic acid and its derivatives are commonly used in the synthesis of benzodiazepines and benzothiazepines. Formation of the desired seven-membered ring is usually achieved through an intramolecular amidation. 

After removal of the Fmoc group from resin 598 with 20% piperidine in DMF for 30 min, the amino acid loaded Wang resin 599 was treated with 2-aminobenzoimine 600 in 

SOLID-PHASE SYNTHESIS OF HETEROCYCLES FROM PEPTIDES AND AMINO ACIDS 

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Many seven-membered ring heterocyclic derivatives show pharmacological activity, and many, for example the benzodiazepines, nevirapine (anti-HIV), trineptine (antidepressant) and artemisinin derivatives (anti-malarial) are used clinically. The number of papers reporting pharmacological activity of new compounds or pharmacological mode of action studies continues at a significant rate. 

Further Six-Membered and Seven-Membered Ring Heterocycle Mimics... 

The Mannich reaction consists on the condensation of a CH-activated compound with a primary or a secondary amine and a non-enolizable aldehyde or ketone to afford p-aminocarbonyl derivatives known as Mannich bases (Scheme 20). This sequence is of great use for the constmction of heterocyclic targets, as illustrated for example by the Robinson-Schopf synthesis of tropinone in 1937 or by the preparation of some azabicyclo[3.3.1]nonanones or pyranocoumarine derivatives (Fig. 1) [100]. In the following, representative recent examples of the formation of five- to seven-membered ring heterocycles will be presented. 

Thermolysis of the tricyclic azetidines (5 X = 0, NC02Et, S or CH2) in solution gives the seven-membered ring heterocycles (6) in high yield (83CC941). 

VI. Compounds from Seven-Membered Ring Heterocycles Containing Only... 

There are now two possible routes to the final product. Reductive elimination would insert the new alkyne into one of the old C-Co bonds and form a seven-membered ring heterocycle. This could close in an electrocyclic reaction to give the new six-membered ring with the cobalt fused on one side and hence the cobalt complex of the new benzene. 

Likewise, reaction of the seven membered ring heterocyclic iminophosphoranes 9 with phenyl isocyanate gives the corresponding carbodiimides 10. ... 

The use of seven-membered ring heterocycles in new medicinal agent design is likely to continue, especially in the context of the search for greater structural novelty from combinatorial synthetic methods. This promises to be a challenging area for the future. 

In more modern times, the first successful anti-ulcer drug, cimetidine 3, with its ability to block histamine synthesis in the stomach, is an imidazole and the classical anti-depressant valium 4 has a seven-membered ring heterocycle that is not (quite) aromatic. 

Oxepin 1, thiepin 2 and azepine 3 are the parent compounds of the seven-membered heterocycles with one heteroatom. Of the seven-membered ring heterocycles with several heteroatoms, only diazepines e.g. 1,2- and 1,4-diazepines 4 and 5 will be discussed. 

Burger, K. Meffert, A. Seven-membered ring heterocycles, IV. Thermol3ftic behavior of... 

Wilckens, K., Uhlemann, M. and Czekehus, C. 2010. Gold-catalyzed cnseven-membered ring heterocycles. Chem. Eur. J. 15 13323-13326. 

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