Synthesis and biological evaluation of pentacyclo[5.4.0.02,6.03,10.05,9]undecane derivatives as potential therapeutic agents in Parkinson's disease

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

“…The combined organic layers were washed with water (50 mL) and dried with MgSO 4 .E vaporation of the organic solvents yielded the desired compound as ab rown-yellow oil (82 mg, 82 %). C 18 Rel-(1R,2S,7R,8S)-6-(benzylimino)tricyclo[6.2.1.0 2,7 ]undec-9-en-3-one (9):C ompound 4 (0.3 g, 1.7 mmol) was dissolved in THF (20 mL). The mixture was cooled to 0 8Cw ith an external ice-water bath with stirring.…”

“…The combined organic layers were sequentially washed with water (50 mL), aqueous NaHCO 3 solution (100 mL), and again with water (50 mL) and dried over MgSO 4 .T he organic layer was evaporated, yielding the product as ab rown oil (yield:3 2mg, 40 %). C 18 Rel-(2R,3S,4S,5S,6S,10S,1R,9R)-2-(benzylamino)-3,6-epoxytricyclo[6.2.1.0 5,10 ]undecan-9-ol (12):C ompound 11 (100 mg, 0.3 mmol) was dissolved in am ixture of MeOH (12 mL) and THF (60 mL). To the mixture, NaBH 4 (11mg, 0.3 mmol) was added and stirred at room temperature for 1.5 days.…”

“…The oil was dissolved in dry benzene and placed under Dean-Stark conditions for 4h.T he benzene was evaporated, and the crude product was purified by silica gel column chromatography using CH 2 Cl 2 /EtOAc/hexane (1:3:1) as eluent, yielding compound 9 as ab rown oil (yield:1 7mg, 4.1 %). C 18 ]undec-9-en-3-one (10):C ompound 9 (80 mg, 0.38 mmol) was dissolved in am ixture of MeOH (12 mL) and THF (60 mL). To the final solution, NaBH 4 (0.03 g, 0.76 mmol) was added and stirred for 36 ha tr oom temperature.…”

“…[24][25][26] Numerous derivatives of this cage molecule have been synthesised and have shown considerable NMDA receptor and calcium channel inhibitory properties. [18][19][20]27] The medicinalp roperties of structurally related tricycloundecane derivatives, which are open cage or rearranged polycyclic cage moieties, have not yet been explored. These novel derivatives are structurally similar to NGP1-01 and MK-801,a nd provide the possibility to develop another group of cage-like derivatives with potential NMDAr eceptor and VGCC inhibitory activities.…”

“…[18][19][20] The polycyclic compounds are uncompetitive NMDA receptor inhibitors with established neuroprotective properties and low toxicity profiles. These properties make them attractive for the development of new therapeutic agents in this field.…”