Natural product and medicinal chemistry

我们建议与Arnason集团共同继续我们成功的生物勘探方法。(1)我们特别计划调查七种以前未被调查过的哥斯达黎加树种，这些树种被认为具有抗癌活性。我们已经收集了两个物种的树叶、木材和树皮，不久将开始生物测定指导分离。(2)我们在魁北克北部昂加瓦湾海岸采集的藻类乙基提取物中发现了一种非常有活性的抗疱疹/抗生物成分，即由半乳糖、甘油和β-亚麻酸组成的糖脂。我们建议合成和评估一小类代谢更稳定的C-糖苷类似物。(3)我们还将在与传统治疗师讨论后，从伯利兹采集的胡椒科植物中分离出一种非常有效的抗癫痫提取物，并对其结构进行鉴定。半纯化的提取物具有与目前在加拿大使用的抗癫痫药物的活性相当的GABA-T生物测定。假设结构不太复杂，我们将开始对其合成和类似物的合成进行研究。(4)我们还将继续我们对稀有的哥斯达黎加树木Ruptillicarpon caracolito的研究，以探索其他成分，可能有助于揭示我们以前从该物种树皮中分离出的高度罕见的螺环CD-环三萜类化合物的生物合成。

We propose to continue our successful bio-prospecting approach jointly with the Arnason group. (1) In particular we plan to investigate up to seven previously uninvestigated Costa Rican tree species with reputed anti-cancer activity. We have already collected leaves, wood and bark of two species and will begin bio-assay guided isolation shortly. (2) We have identified the very active anti-herpes/anti-biotic component found in the ethyl extracts of algae harvested on the shores of Ungava Bay in Northern Quebec as a glycolipid built from galactose, glycerol and ?-linolenic acid. We propose to synthesize and evaluate a small family of the metabolically more stable C-glycoside analogs. (3) We will also isolate and determine the structure of a very active anti-epileptic extract isolated from a Piperaceae species collected in Belize after discussion with traditional healers. The semi-purified extract has activity comparable to that of the currently used anti-epileptic drug in Canada using the GABA-T bio-assay. Assuming that the structure is not overly complex we will initiate studies towards its synthesis and the synthesis of analogs. (4) We will also continue our studies of the rare Costa Rican tree Ruptilliocarpon caracolito to probe for additional components that may shed light on the biosynthesis of the highly unusual spiro CD-ring triterpenoids that we have previously isolated from the bark of this species.