Haperforin G的不对称全合成

Haperforin G is a complex limonoid isolated from the leaves of Harrisonia perforata (Blanco) Merr.(Simaroubaceae) collected in the Daklak district in Central Vietnam. Its structure features are :1) it is possessing a 6/5/6/5/7-fused ring system, including a [3.2.2] bridged ring and aγ-lactone. 2) six chiral centers including two all-carbon quaternary centers present in its structure. 3) it is highly oxidized and contains a tertiary hydroxyl group at the δ position of theα, β -unsaturated ester group. In a word, it is a B,D-seco-C16-degraded C-25 type highly rearranged liminoid..In this case, our attention was attracted by these features: 1) as a target of total synthesis, it has novel and complicated structure which making the its total synthesis challenging. 2) as a representive of seco-liminoids, its asymmetric total synthesis study can provide a method for studying the total synthesis of this family of natural products with similar skeletal structure and support biosynthetic hypothesis and bioactive study of this natural products family. the total synthesis of Haperforin G is also providing opportunity for developing new reactions and novel methodolgies.

Haperforin G是从越南中部的Daklak区苦木科植物牛筋果中分离得到的一个结构复杂的柠檬苦素分子，其结构具有以下特点：1.该分子具有[6-5-6-5-7]并环骨架结构，其中包含一个[3.2.2]桥环骨架和一个五元内酯环结构；2.分子结构中含有6个手性中心，其中2个是季碳手性中心；3.该分子骨架高度氧化，而且具有一个位于α，β不饱和酯基δ位的3级羟基。总的来说，它是一个B,D开环、降16位碳原子、骨架高度重排的C-25型柠檬苦素。.Haperforin G的结构特点引起了我们极大的兴趣：1.作为全合成的目标分子，其复杂新颖的化学结构极具挑战性；2.作为第三类环开裂柠檬苦素，其不对称全合成研究可以为该家族具有类似骨架结构的天然产物的全合成提供方法，同时为研究该分子及其同家族天然产物的生物活性和生源合成途径打下基础；3.对该天然产物的全合成研究可以为发现新反应和新方法提供机会。

(+)-Haperforin G是从苦木科植物牛筋果（Harrisonia perforate）中分离得到的一个结构复杂的柠檬苦素类天然产物。分子中含有一个7-6-5-6-5骨架结构，两个全碳手性中心和一个[3.2.2]桥环骨架结构，在合成上具有相当的挑战性。.基于该分子的结构特点，我们利用汇聚式合成策略，以羧酸α位直接的不对称烷基化反应、Pauson-Khand反应、碘原子转移反应以及可见光介导的光氧化还原催化剂催化的分子间Giese反应为关键反应，通过20步反应最终实现了该分子的全合成。该合成提出并实现了通过切断中心C环来汇聚式完成柠檬苦素全合成的合成策略，为该家族分子简洁、高效的全合成提供了一种新的思路以及构建办法。