The Biomimetic Synthesis of (-)-Kaur-16-en-19-oic Acid

本文尝试了通过阳离子烯烃多环化反应对映选择性地仿生全合成贝壳杉-16-烯-19酸。手性将通过Sharpless不对称环氧化反应的对映选择性环氧化物形成来引入。该关键反应将在一个单一的协同反应步骤中同时产生三个碳环和五个相邻的立体中心，并有望在产物分子中产生高的对映选择性。目标是一种天然产物，具有类似于植物生长激素赤霉素的生物活性。它通常与赤霉素一起沿着从各种植物物种中分离，并且可能是赤霉素生物合成的中间体。所提出的合成改进后发表的合成立体选择性的策略，将支持目标化合物的成功合成。预计该提案的成功完成将允许开发一种通用的获取方法，该方法可针对与具有更显著（即抗微生物、杀锥虫和抗HIV）生物活性的（-）-贝壳杉-16-烯-19-酸相关的其他二萜类天然产物靶标进行修改。

The biomimetic total synthesis of (-)-kaur-16-en-19 oic acid will be attempted enantioselectively via a cation olefin polyannulation reaction. Chirality will be introduced by enantioselective epoxide formation via Sharpless asymmetric epoxidation. The key reaction will create three carbocycles and five contiguous stereocenters simultaneously in a single concerted reaction step and is expected to produce high enantioselectivities in the product molecule. The target is a natural product that has biological activity similar to gibberelines a plant growth hormone. It is often isolated from various plant species along with gibberellines, and may be an intermediate in gibberellin biosynthesis. The proposed synthesis improves upon published synthesis by Stereoselective strategies that will support a successful synthesis of the target compound. It is anticipated that a successful completion of the proposal will allow for the development of a general method of access that is modifiable for other diterpenoid natural product targets related to (-)-kaur-16-en-19-oic acid that possess more significant (i.e. anti- microbial, trypansomicidal and anti-HIV) biological activity.