Arisandilactone A 的不对称全合成

Arisandilactone A is anortriterpenoid isolated from the fruits of Schisandra arisanensiwhich distributed in the mountainous area of Taiwan.Its structure features are: 1) it is possessing a 5/5/7/5/8/5-fused hexacyclic ring system which was firstly reported in natural product isolation. 2) 12 chiral centers including 3 quarternary carbon centers and an all substitued tetrahydrofuran present in its structure. 3) a novel bridge head carbon-carbon double bond was in its [5,2,1] core structure.4) it is highly oxidized and contains all typical rings. In this case, our attention wasattracted 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 Schisandraceae natural products, its asymmetric total synthesis study can support biosynthetic hypothesis and bioactive study of this natural products family.3) as our gourp has developed a general synthetic route for this natrual products family, we wish to apply the general route in the total synthesis of Arisandilactone A and realize the diversity-orented synthetic strategy. 4) the total synthesis of Arisandilactone A is also providing opportunity for developing new reactions and novel methodolgies.

Arisandilactone A是从台湾地区阿里山五味子果实中分离得到的降三萜类化合物，其结构具有以下特点：1. 具有复杂的[5-5-7-5-8-5]并环骨架结构，这在天然产物中首次报道；2. 结构中含有12个手性中心，包含3个季碳手性中心及一个全取代的含氧五元环；3. 分子中心的[5,2,1]桥环骨架中含有独特的桥头双键；4.该分子高度氧化，具有各种典型的环状结构。Arisandilactone A的结构特点引起了我们的兴趣：1. 作为全合成目标分子，Arisandilactone A的结构复杂而新颖，极具挑战性；2. 该分子为五味子家族代表性天然产物，对它的不对称全合成可为研究该家族天然产物的生源合成途径以及生理活性打下基础； 3.本小组曾发展了一条普适性合成路线，我们将在该分子的不对称全合成中尝试实现该路线多样性导向的全合成；4. 该分子的全合成过程为发现新反应、新方法提供了机会

Arisandilactone A是结构非常复杂的五味子降三萜类天然产物，具有5-5-7-5-8-5并环骨架，其中包含一个具有桥头双键的[5.2.1]双环结构，密集分布12个手性中心（含3个四级碳手性中心），分子骨架高度氧化，形成复杂复合的官能团系，在合成上具有相当的挑战性。在本课题组此前发展的针对该家族天然产物的多样性导向合成路线基础上，我们进一步发展了该策略，并完成了19-脱氧-Arisandilactone A的首次全合成。该合成从天然手性源出发，经Simmons-Smith环丙烷化扩环反应，烯烃关环复分解（RCM）反应，铜催化分子内环丙烷化反应，串联Mukaiyama羟醛缩合-homo Michael加成反应构建了分子核心骨架，最终以37步完成了合成工作。该合成首次实现了7-8-3全碳并环的构建及其到7-5-8-5并环的仿生转化，完善了针对该家族天然产物的多样性导向合成策略