Nephilatoxins (NPTX-1〜12) isolated from the venom of Joro spider (Nephila clavata) have been characterized as structurally new type of neurotoxins consisted of an aromatic acid, amino acids, and some polyamines. These toxins induce histamine release from rat peritoneal mast cell and exhibit potent blocking activities toward glutaminergic neurotransmission in the lobster legs. We have reported the first and efficient syntheses of NPTX-9,10,11, and 12 by the use of azide intermediates (1 and 2) which played key roles in the construction of the characteristic polyamine components such as cadaverine and putreanine. By designing a novel azide compound 3 as 9-aminopropylputreanine equivalent, we were successful in the first synthesis of NPTX-8 (Scheme 2). We also synthesized NPTX-7, the only spider toxin containing an acidic amino acid as a component, according to Scheme 3. In addition enantiomers of NPTX-8 and NPTX-12, i.e., D-NPTX-8 and D-NPTX-12 containing D-asparagine, have been synthesized to investigate the structure-toxicity relationship. From the biological tests of the seven synthetic toxins (paralyzing activity against Blattela germanica L.), it was revealed that the reported order of Nephilatoxins should be revised as NPTX-12>NPTX-10>NPTX-8> NPTX-11>NPTX-9. Interestingly, D-NPTX-8 and D-NPTX-12 have been shown to exhibit considerably potent glutaminergic blocking activities. Further synthetic studies on other spider toxins and analogues are in progress.