Synthesis and Structural Analysis of Novel Neuroprotective Pentacyclo[5.4.1.0~(2,6).0~(3,10).0~(5,9)]undecane- and Adamantane-Derived Propargylamines

摘要

In this article we present a detailed structural investigation of novel polycyclic pentacyclo[5.4.1.0~(2,6). 0~(3,10).0~(5,9)]undecane and adamantane propargylamine hybrid molecules. The structural characterization of these compounds was performed using MS, FT-IR and NMR spectroscopy in combination with X-ray diffraction analysis. The single crystal X-ray analyses of four synthons (6, 8-10) are presented; 8-(N)-propargylamino-8,11-oxapentacyclo-[5.4. 1.0~(2,6).0~(3,10).0~(5.9)]undecane (compound 6 crystallized in the monoclinic system, unit cell parameters: a = 20.737(2) ?; b = 8.127(1) ?; c= 12.606 (1) ?; β = 92.360(2)°; V = 2122.8(3) ?~3; Z = 8); 11-hydroxy-(N)-propargyl-8,11- azapentacyclo[5.4.1.0~(2,6).0~(3,10).0~(5.9)]undecane (compound 8 crystallized in the monoclinic system, unit cell parameters: a = 7.9624(6) ?; b = 14.9332(6) ?; c = 9.6162(7) ?; β = 109.029(3); V = 1080.9(2) ?~3; Z = 4); 1-methyl-11- hydroxy-(N)-propargyl-8,11-azapentacyclo[5.4.1.0~(2,6).0~(3,10).0~(5.9)] undecane (compound 9 crystallized in the monoclinic system, unit cell parameters: a = 7.732(1)?; b = 15.148(2)?; c = 9.864(1) ?; β = 101.728(3)°; V = 1131.3 (2) ?~3; Z = 4); and an adamantane derivative, N,N-dipropargyladamantan- 1-amine (compound 10 crystallized in the orthorhombic system, unit cell parameters: a = 34.098(4) ?; b = 6.825(1) ?; c = 10.979(1) ?; V = 2555.0(5) ?~3; Z = 8). From the X-ray analyses it is clear that the polycyclic structures had different modes of intermolecular interaction and molecular stacking. Compound 9 exhibited a cis configuration between the OH and CH_3 moieties as expected in view of potential steric hindrance and the electron density effects of the methyl moiety on the initial amination reaction. These hybrid molecules exhibited significant anti-apoptotic activity and could thus find application as neuroprotective agents.