Total Syntheses of Spidamine and Joramine, Polyamine Toxins from the Joro Spider, Nephila clavata

Abstract

In order to confirm the structures of spidamine and joramine, identified from the venom of a spider (Nephila clavata), we convergently synthesized both compounds, which have a common side chain of N-(L-asparaginyl)-N'-(3-aminopropyl-β-alanyl)-1, 5-pentanediamine. A synthon of the common side chain was synthesized by starting with n-propanolamine which was converted to 7-azido-N-benzyloxycarbonyl-4-azaheptanoic acid N-hydroxysuccinimidyl ester. The ester was coupled with tert-butyloxycarbonyl-L-asparaginyl-1, 5-pentanediamine to give the synthon of the common side chain. In the final synthesis of spidamine, the synthon of the common side chain was reacted with 2, 4-dibenzyloxyphenylacetic acid N-hydroxysuccinimidyl ester, obtained by Willgerodt-Kindler reaction of 2, 4-dihydroxyacetophenone. The protected spidamine was catalytically hydrogenated to remove protective groups, affording spidamine itself in 13% yield from n-propanolamine. In the final synthesis of joramine, the synthon of the common side chain was reacted with 4-benzyloxyphenyl acetic acid N-hydroxysuccinimidyl ester. The protected joramine was also catalytically hydrogenated to produce joramine itself in 11% yield.The conformations of both synthesized compounds were analyzed by ¹H-NMR and ¹³C-NMR. Their blocking activities on glutamate receptors were examined using labster neuromuscular synapses.