87(P-44) クモ毒アシルポリアミン類の新汎用合成法(ポスター発表の部)

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概要

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• Acylpolyamine toxins are a class of compounds isolated from venoms of spiders and wasp. The novel structural features and remarkable inhibitory effect on glutamate receptors prompted much interests in chemical and pharmacological studies of the acylpolyamine toxins. Much efforts have devoted to synthesize these toxins and their analogs to elucidate the structure-activity relationships (SAR) and mode of action, which would lead to useful analogs for neurobiological research and developing therapeutic agents and insecticides. The recent studies by new highly sensitive analytical methods using LC-MS and MS/MS revealed that the Nephila and Nephilengys spider venom glands contain a complex mixture of up to 40 closely related acylpolyamine toxins. A majority of the toxins have not been detected previously by the classical analytical method, which prompted renewed interest in the SAR and mode of action for acylpolyamine spider toxins. In this point of view, we report here a novel synthetic method for acylpolyamine spider toxins which is highly efficient and versatile for all structural types of naturally occurring toxins and their analogs. The structures of the Nephila and Nephilengys spider toxins are consisted of three elements: lipophilic head; polyamine backbone; polyamine chain terminal, and they linearly connect in this order. There are a variety of each element and combination of each element results in a complex mixture of the venom gland constituents. These toxin structures are classified into the generalized structures Type A-E based on the distinct polyamine backbone structure. Figure 1 shows the representative toxins for each type. This classification is suitable for synthetic strategy; that is, construction of polyamine backbone, followed by successive connection of lipophilic head and polyamine chain terminal would afford a variety of natural toxins as well as their analogs. On the other hand, Fukuyama et al. reported that the 2-nitrobenzenesulfonamide (nosyl, Ns) protecting group is exceptionally versatile for the preparation of a variety of secondary amines, and utilized this protocol to the synthesis of the spider toxin HO-416b, demonstrating its utility for the synthesis of acylpolyamine toxins. Our synthetic plan is based on the structural classification of the Nephila and Nephilengys spider toxins and applies Fukuyama's protocol to rather complicated acylpolyamine spider toxins 1-5, aiming at the efficient and versatile synthesis of all structural types of naturally occurring toxins and their analogs.

• 天然有機化合物討論会の論文
• 2001-09-01

著者

• 紺野 勝弘

  帝京大薬

• 二瓶 賢一

  帝京大薬

• Kato Massuo

  サンパウロ大化

• 紺野 勝弘

  サンパウロ州立大学リオクラーロ校応用トキシノロジーセンター

• 山根 鉄男

  ブタンタン研:cat

• 二瓶 賢一

  サンパウロ大化

• Palma Mario

  サンパウロ州立大生物

• Palma Mario

  サンパウロ州立大生物:cat

• Palma Mario

  サンパウロ州立大

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