An efficient synthetic strategy to obtain 1‐chloro‐Cs‐trishomocubane and 1‐chloro‐D3‐trishomocubane is described. 1‐Chloro‐Cs‐trishomocubane is synthesized by a regioselective Diels–Alder reaction, and B3PW91/6‐31G(d,p) calculations offer a plausible explanation of the reaction mechanism. Surprisingly, 1‐chloro‐Cs‐trishomocubane does not undergo an acid‐catalyzed rearrangement to form 1‐chloro‐D3‐trishomocubane and was obtained by chlorosulfation of Cookson's diketone. A possible mechanism of the reaction involving the formation of Cs‐ and D3‐trishomocubane nonclassical cations was proposed on the basis of a mechanistic [B3PW91/6‐31G(d,p) and MP2/cc‐pVDZ] study.
GABA was discovered to play an important role as the major inhibitory neurotransmitter in the adult mammalian CNS 60 years ago. The conformational flexibility of GABA is important for its biological function, as it has been found to bind to different receptors with different conformations. In an effort to increase the lipophilicity and to reduce conformational flexibility of GABA itself, a polycyclic or cage hydrocarbon framework can be introduced into the 3D structure of GABA in order to better control the binding. This article explores the available synthetic methods, properties and activity of carbocyclic (cyclopropanes, cyclobutanes and cyclohexanes) and cage (adamantane and others) hydrocarbons - analogs of GABA with conformationally rigid carbon skeletons.
A number of Cookson's diketone ( Cs-trishomocubane-8,11-dione) derivatives were synthesised and introduced into the reaction with chlorosulfonic acid to give previously unknown polysubstituted D3-trishomocubanes (pentacyclo[6.3.0.02,6.03,10.05,9]undecanes) – chiral analogues of the parent cubanes. In the case of 1,9-dibromo- Cs-trishomocubane-8,11-dione, the reaction proceeded with conservation of both carbonyl groups selectively affording 3-bromo-6-chloro- D3-trishomocubane-4,7-dione whose distinct substitution pattern was confirmed by means of X-ray structural analysis.
Abstract.Binding of blockers to the Influenza A ion-channel is studied using automated docking calculations. Our study suggests that studied cage compounds inhibit the M2 ion channel by binding to the His37 residue. The adamantane cage fits into a pocket formed by Trp41 residue, while the hydrogen bond is formed between hydrogen atom of ammonium nitrogen and the nitrogen of histidine residue. This finding is supported by experimental data and should help to obtain better understanding of the inhibition mechanism of the Influenza A M2 ion channel.
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