Synthesis of accromelic acids and their derivatives

从一种有毒的蘑菇中分离出微量的丙烯酸酯A和B，其结构主要由波谱数据推断，并经合成得到确证。合成的目的是为了消除立体化学，然后选择红藻氨酸作为起始材料，因为它的绝对构型是已知的。为了将异丙烯基团转化为吡啶酮，提出了1，5-二羰基化合物经Pummerer重排反应合成吡啶的新方法，并提出了新的有效的反应条件。合成完成后发现，三种丙烯酸手性传感器的绝对构型与海人藻酸完全相同。这些合成使二次测定成为可能，并揭示了它们最有效的神经兴奋特性。因此，试图更有效地合成这些酸及其衍生物，以寻找它们的拮抗剂和激动剂。I)利用丝氨酸的手性控制在吡咯环上构建三个手性中心的研究。Ii)为了验证哪些部分结构有助于表现出强烈的神经兴奋，我们合成了几个衍生物，并检测了它们对谷氨酸的兴奋反应的相对强度或增强作用。结果表明，在吡咯烷环的第4位上需要一个具有高电子密度的基团来提高生物活性。3)尝试合成了以苯酚取代吡啶酮的丙烯酸衍生物，并进行了红藻氨酸异丙烯基转化为苯酚的模拟实验。对于吡咯烷环的立体选择性结构，我们还考察了9-内酯的跨环自由基环选择，得到了双环[9.3.0]正庚烷反应和杂Diels-Alder反应，但没有得到明确的结果。

A minute amount of acromelic acid A and B was isolated from a poisonous mushroom and their structures were deduced mainly from spectroscopic data and confirmed by the synthesis. The syntheses were designed to clear the stereochemistry and then kainic acid was chosen as the starting material because its absolute configuration was known. In order to convert isopropenyl group into pyridone, a new pyridine synthesis through 1,5-dicarbonyl compound using Pummerer rearrangement and a new effective condifions in the rearrangement of pyridine Noxide into pyridone were developed. The completion of the synthesis revealed the absolute configurations of three chiral senters of acromelic acid were the same as those kainic acid. These synthesis made bisassay possible and their most potent reuroexcitatory properties were disclosed. The more effective synthesis of the acids and their derivatives were thus attempted to look for their antagonists and agonists. i) Construction of three chiral centers on pyrrolidine ring employing control by the chirality of serine were under inverstigation. ii) To check which partial structure contributes to exhibition of strong neuroexcitation, several derivatives were synthesized and the relative strength or potentiation of excitatory responses to glutamate induced by them was examined. It was consequently revealed that a group possessing high density of -electron was necessary at the position 4 of pyrrolidin ring for enhancement of the bioactivity. iii) The syntheses of derivatives of acromelic acid carring phenol instead of pyridone was attempted and model experiments for conversion of isopropenyl group of kainic acid into phenol are now going on. For the stereoselective construction of pyrrolidine ring, trans annular radical ring chosure of 9-menbered lactone leading to bicyclo[9.3.0]nonane syntem and hetero- Diels-Alder reaction are also examined but any definite result is not obtained so for.