Synthesis and Biological Evaluation of Rigid Polycyclic Derivatives of the Diels-Alder Adduct Tricyclo[6.2.1.02,7]undeca-4,9-dien-3,6-dione

Abstract

Part of our research program concentrates on the discovery of new bioactive compounds prepared either by total synthesis or molecular transformation of compounds with bioactivity profiles. In this work we have focused our interest on chemical transformations of the Diels-Alder adduct tricyclo[6.2.1.0 2,7 ]undeca-4,9-dien-3,6-dione in order to obtain cage-like compounds and derivatives, followed by an evaluation of their biological activity.

Tricycloundecane Derivatives as Potential N‐Methyl‐D‐aspartate (NMDA) Receptor and Voltage‐Gated Calcium Channel Modulators

“…This was also observed in attempts to conjugate benzylamine to the 6-keto of the 3-hydroxyltricycloundecane derivative 5 which were unsuccessful even under extreme temperatures, high pressure, and microwave irradiation. The reduction of compounds 7a,b and 9 using sodium borohydride as reducing agent yieldedc ompounds 8 and 10,r espectively.Acomparison of the NMR data for 8 and 10 with that of similar tricyclic keto esters described by Marchand et al that contained an endo-3-dinitrobenzoyloxy group, [30] andb yI to et al,w hich contained an endo-3-trimethylmethoxyphenylcarbonyloxy group, [28] confirmed the structures proposed for 8 and 10 (Scheme 1). Interestingly,o nly the endo-3-benzylamine derivative 8 was obtained from reduction of the isomeric mixture of 7a,b.T his might indicate that we were ablet os electively reduce 7b,o rt hat only the endo-3-benzylamine 8 was isolated from the reactionm ixture.…”

“…[29,30] The treatment of 5 with N-bromosuccinimide resulted in ac losedring bromoether derivative 6 in nearly quantitative yield. [28,31] The structures of compounds 3-6 were confirmed on the basis of their respective melting points, NMR and IR spectra,a nd literature references; [28][29][30][31] they served as precursors for the novel tricycloundecylamined erivatives reported herein.…”

“…The S N 2n ucleophilic substitution at the bromide with benzylamine resulted in inversion of configuration. Compound 12 was obtained by reduction of the carbonyl group of 11 using sodium borohydride, and its structure and stereochemistry were confirmed by comparing its NMR data with those of compounds 6, 11,a nd as imilar6 -epoxy-9-hydroxytricycloundecane structure proposed by Ito et al [28] The yields of compounds 7a,b, 9,a nd 10 werev ery low,but sufficientquantities were obtained for structural elucidation and biological evaluation. We are currently exploring ways in which we can optimise the synthetic procedures for these compounds to increase yields.…”

“…The precur- www.chemmedchem.org sor molecule, an endo form of tricycloundeca-4,9-diene-3,6-dione (3), has ah igh degree of symmetry that allows facile selective reactions at one or both carbonyl groups by means of classical and non-classical reagents. This molecule was synthesised by using the cycloaddition reaction described by Ito et al in 2007. [28] This procedure yieldedc ompound 3 as the endo isomer after recrystallisation from hexane as pure yellow crystals.…”

“…This molecule was synthesised by using the cycloaddition reaction described by Ito et al in 2007. [28] This procedure yieldedc ompound 3 as the endo isomer after recrystallisation from hexane as pure yellow crystals. In the presence of zinc and glacial acetic acid, 3 was selectively reduced to yield 4.…”