STRATEGIES FOR TETRODOTOXIN AND AZADIRACHTIN

河豚毒素(TTX)和印楝素有许多共同的特征。 两者都是民间传说中的传奇，前者被认为是 日本河豚，后者是印尼花的神秘成分 树，数千年来在整个印度次大陆作为一种 杀虫剂和杀菌剂。这两种化合物都顶住了几十年的努力 几个大洲的著名化学家致力于结构阐明， 这两种结构最终都是通过物理而不是化学来解决的 方法：研究方法。 TTX通过阻断可兴奋膜的离子通道发挥作用，并 这一特性非常有价值，因为它允许生物化学家识别和 分离这些鲜为人知的生物结构。就目前而言 河豚是实验室中使用的TTX的主要来源，以及 非常需要一种灵活的合成方法，以允许 用于结构/活性研究的类似物的制备。从… 这样的研究可以更好地理解脉冲的传递 通过可兴奋的膜就会出现。 印楝素可从其天然来源获得更多的量 TTX，所以化学转化已经揭示了一些 其结构/活动概况的各个方面。但由于它的复杂性 在分子方面，还需要做更多的工作。除了将其用于 由于其杀虫特性，印度农村人使用印尼树来进行牙科治疗 关心。因此，它们咀嚼着树枝的柔软，汁液起到了一种 牙膏和牙线一样的纤维。一种德国牙膏含有 最近出现在市场上，其中包括印楝素。这个 这种牙科护理的化学基础尚不清楚。 这两个分子都可以被认为是“稠密官能化的碳环”，一个 我们实验室一直在开发的天然产品类别 在我们的碳水化合物到碳环背景下的方法学 变形。几年来，我们已经展示了自由基方法来 是碳水化合物操作的理想选择，因为 这些物质中存在的多个官能团通常是 在这些反应中没有受到影响。针对丰富的功能化 在TTX和印楝素中，自由基程序的应用 因此，它们的建设与我们的利益产生了共鸣，实际上 我们对这两个分子的方法，自由基方法学的特点是 突出表现在几个关键的转变上。同样源远流长 人们感兴趣的是Diels Alder反应，自从我们的实验室显示 在利率和收益率方面存在着巨大的差异 碳水化合物α-烯酮及其碳环对应物。它是 因此，我们对印木素的研究将两者结合在一起是非常合适的 在这些方法中，自由基法和Diels Alder法。

Tetrodotoxin (TTX) and azadirachtin share many common characteristics. Both are legendary in folklore, the former as the potent toxin of the Japanese puffer fish, the latter as the mysterious ingredient of the neem tree, used for thousands of years throughout the Indian subcontinent as a insecticide and germicide. Both compounds defied several decades of effort by eminent chemists on several continents towards structure elucidation, both structures being finally solved by physical rather than chemical methods. TTX exerts its action by blocking ion channels of excitable membranes, and this property is highly valued since it allows biochemists to identify and isolate these poorly understood biological structures. At the present time the puffer fish is the major source of the TTX used in laboratories, and there is a great need for a flexible synthetic approach that will permit the preparation of analogs for use in structure/activity studies. From such studies a better understanding of the transmission of impulses through excitable membranes will emerge. Azadirachtin is available from its natural source in greater quantities than TTX, and so chemical transformations have already shed light on some aspects of its structure/activity profile. But because of the complexity of the molecule, far more needs to be done. In addition to using it for its insecticidal properties, rural Indians use the neem tree for dental care. Thus they chew the soft branches of the tree, the juice acting as a dentifrice and the fibers as dental floss. A German toothpaste has recently appeared on the market which incorporates azadirachtin. The chemical basis for this dental care has yet to be clarified. Both molecules may be regarded as "densely-functionalized carbocycles", a category of natural products for which our laboratory has been developing methodology in the context of our carbohydrate-to-carbocycle transformations. For several years we have shown free radical methods to be ideal for carbohydrate manipulations in view of the fact that the multiple functional groups present in these substances are usually unaffected during these reactions. In view of the rich functionalization of TTX and azadirachtin, the application of free-radical procedures for their construction therefore resonates with our interests, and indeed in our approach to both molecules, free radical methodology features very prominently for several key transformations. Also of long standing interest is the Diels Alder reaction, ever since our laboratory showed that there are dramatic differences in rates and yield between carbohydrate alpha-enones and their carbocyclic counterparts. It is therefore very appropriate that our approach to azadirachtin combines both of these methodologies, free radical and Diels Alder.