A Unified Approach to the Diterpenes of Pseudopterogorgia elisabethae Featuring a Reagent Free Cascade Sequence

海洋环境中生活着许多生物。有些是我们大家都熟悉的，比如龙虾和虾，而另一些可能只有少数海洋生物学家知道。一种生活在加勒比海浅海中的海鞭，介于这两个极端之间。它也被称为紫色褶边，通常装饰在热带鱼的鱼缸里——它的手臂在紫外线的照射下闪烁着彩虹般的光芒。海洋生物的化学是迷人的，作为一门学科，它在很大程度上还处于起步阶段。通过研究一种海洋生物体内的化学混合物，科学家们可以帮助解开它的一些秘密。一种看似毫无防御能力的动物是如何保护自己免受捕食者攻击的？一种选择是制造毒药——一种水生形式的化学战！没有眼睛和耳朵的生物是如何找到彼此约会和交配的？使用令人兴奋的“香水”通常是答案。对人类来说，这些化学物质不太可能起到毒药或香水的作用，因为我们的化学成分是完全不同的。这些差异提供了机会。例如，在紫褶草产生的化学物质中，有两种被发现对导致最严重疟疾的寄生虫是致命的。另一种显示出抗肺结核的强效活性。甚至在雅诗兰黛（Estee Laude）销售的抗皱面霜中也发现了紫色褶边的化合物！为什么海鞭会产生这样的化合物仍然是一个谜，尽管它们对人类的潜在好处是清楚的。从海鞭草中提取药用成分既不环保也不实用。从正确的角度来看，一吨海鞭所能提供的抗疟疾药只比一克多一点。因此，这种分子的化学合成提供了获得它们的唯一可行方法。我们的目标是在实验室中制造出五种最重要的“紫色褶边分子”。这是一个具有挑战性的目标，因为每个原子由大约50个原子组成，而这些原子有数十亿种排列方式。为了达到我们的目标，这50个原子中的每一个都必须以与其他49个原子完全相同的方式排列，就像大自然选择组织它们一样。大自然花了数百万年的时间才开发出一种制造这些化合物的方法，而我们正试图在短短三年的时间内制备它们。环境压力团体经常批评化学工业及其产生的废物水平。我们设计的路线使用很少的化学反应，以便将浪费降到最低。我们建议的核心是一个复杂的四个反应序列，一个接一个地传递，没有干预。值得注意的是，这种接力反应或“级联”反应不需要任何试剂，只需在微波炉中加热化合物即可触发。我们的目标是以最少的努力和不浪费的方式取得最大的成效。这并不总是可能的，但我们在努力。

The marine environment is populated by a host of creatures. While some are familiar to us all, such as lobster and shrimp, others may be known to just a few marine biologists. Pseudopterogorgia elisabethae, a sea whip that lives in shallow waters off the Caribbean, falls somewhere between these two extremes. Also known as the Purple Frilly, it commonly adorns tropical fish tanks - its arms shimmering with an iridescent glow under the ultra-violet lighting.The chemistry of marine life is fascinating and as a subject is very much in its infancy. By studying the cocktail of chemicals found in a sea-creature, scientists can help to unravel some of its secrets. How does a seemingly defenceless animal protect itself from predators? One option is to produce poisons - an aquatic form of chemical warfare! And how do creatures with no eyes or ears find one another to date and mate? The use of arousing 'perfumes' is often the answer. To humans, such chemicals are unlikely to act as poisons or perfumes as our chemistry is quite different. These differences provide opportunities. For example, of the chemicals produced by the Purple Frilly, two have been found to be deadly to the parasite responsible for the most severe forms of malaria. Another displays potent activity against tuberculosis. A compound from the Purple Frilly is even to be found in an anti-wrinkle cream marketed by Estee Laude! Why a sea-whip should produce such compounds remains a mystery, though their potential benefit to man is clear.To harvest the sea-whip for its medicinal compounds is neither environmentally sound or practical. To place things in perspective, one tonne of sea-whip would give little more than a gram of the anti-malarial. Consequently, the chemical synthesis of such molecules provides the only viable means of accessing them in quantity. Our aim is to make five of the most important 'Purple Frilly molecules' in the laboratory. It is a challenging goal as each is made up of around fifty atoms, and there are billions of ways these could be arranged. For us to meet our goal, each of the fifty atoms must be positioned relative to the other forty-nine in exactly the same way as Nature chose to organised them. And whereas Nature took millions of years to develop a way of making these compounds, we are seeking to prepare them in just three years. Environmental pressure groups are often critical of the chemical industry and the level of waste they produce. The route we have devised uses very few chemical reactions in order to keep waste to a minimum. Central to our proposal is a complex sequence of four reactions which are relayed, one after the other, and without intervention. Remarkably, that relay or 'cascade' reaction employs no reagents and is triggered by simply heating the compound in a microwave. Our aim is to achieve maximum useful work for minimal effort and with no waste. It is not always possible, but we try.