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

具有无试剂级联序列的 Pseudopterogorgia elisabethae 二萜的统一方法

• 批准号: EP/C006364/1
• 负责人: David Harrowven
• 金额: $ 24.94万
• 依托单位: University of Southampton
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FC006364%2F1
• 关键词: Unified; Approach; Diterpenes; Pseudopterogorgia; elisabethae

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.

海洋环境中居住着大量的生物。虽然有些是我们大家都熟悉的，如龙虾和虾，但其他的可能只有几个海洋生物学家知道。生活在加勒比海浅水区的海鞭--海鞭--介于这两个极端之间。它也被称为紫色褶皱，通常装饰在热带鱼的鱼缸上--它的手臂在紫外光下闪闪发光。海洋生物的化学很吸引人，作为一门学科还处于起步阶段。通过研究海洋生物中发现的化学物质的混合物，科学家们可以帮助揭开它的一些秘密。一种看似毫无防备的动物如何保护自己不受捕食者的伤害？一种选择是制造毒药--一种水生形式的化学战！没有眼睛或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”往往是解决问题的办法。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非常不同。这些差异提供了机会。例如，在紫色褶皱公司生产的化学物质中，有两种被发现对导致最严重形式的疟疾的寄生虫是致命的。另一种显示出有效的抗结核病活性。一种来自紫色褶边的化合物甚至可以在雅诗兰黛销售的一种抗皱霜中找到！海鞭为什么会产生这样的化合物仍然是个谜，尽管它们对人类的潜在好处是显而易见的。采集海鞭以获取其药用化合物既不环保，也不实用。客观地说，一吨海鞭只能产生一克多一点的抗疟疾药物。因此，这些分子的化学合成提供了唯一可行的方法来获取它们的数量。我们的目标是在实验室里制造出五种最重要的“紫色褶皱分子”。这是一个具有挑战性的目标，因为每个原子都由大约50个原子组成，这些原子可以有数十亿种排列方式。为了达到我们的目标，50个原子中的每个原子必须以大自然选择的组织它们的完全相同的方式相对于其他49个原子定位。虽然大自然花了数百万年才开发出一种制造这些化合物的方法，但我们正寻求在短短三年内准备好它们。环境压力组织经常对化学工业及其产生的废物水平持批评态度。为了将废物减少到最低限度，我们设计的路线使用的化学反应很少。我们建议的核心是一个由四个反应组成的复杂序列，这些反应一个接一个地传递，没有干预。值得注意的是，这种接力或“级联”反应不使用试剂，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实现最大限度的有用工作。这并不总是可能的，但我们会努力。

项目成果

Cyclobutenone Rearrangements in the Synthesis of (-)-Colombiasin A

(-)-Colombiasin A 合成中的环丁烯酮重排

• 发表时间: 2008
• 作者: N/a Kemp

Exploring diradical chemistry: a carbon-centered radical may act as either an anion or electrophile through an orbital isomer.

• DOI: 10.1002/anie.201411334
• 发表时间: 2015-04
• 期刊: Angewandte Chemie
• 作者: Théo P. Gonçalves;Mubina Mohamed;R. Whitby;H. Sneddon;D. Harrowven

Cyclobutenone Rearrangements in the Synthesis of (-)-Colombiasin A and (-)-Elisapterosin B

(-)-Colombiasin A 和 (-)-Elisapterosin B 合成中的环丁烯酮重排

• 发表时间: 2008
• 作者: N/a Kemp