Total syntheses of spidamine and joramine, polyamine toxins from the joro spider, Nephila clavata

Article abstract of DOI:10.1248/cpb.44.972

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 lobster neuromuscular synapses.

Full text of DOI:10.1248/cpb.44.972

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