Synthetic Studies on Schisandra nortriterpenoids. Stereocontrolled Synthesis of Enantiopure C-5-<i>epi</i> ABC Ring Systems of Micrandilactone A and Lancifodilactone G Using RCM

A stereocontrolled approach for the construction of ABC ring systems of micrandilactone A and lancifodilactone G has been developed. The synthesis involves construction of an enantiopure functionalized cycloheptene derivative 17 through RCM of the dienol 14 prepared from the known d-mannitol-derived unsaturated ester 12. A remarkable regioselectivity during hydroboration of the cycloheptene derivative 17 was observed during its transformation to the cycloheptanone 20. RCM of the diene 24 prepared stereoselectively from 20 gave the spiro-dihydrofuran 25. The ketal unit in 25 was then converted into the carbinols 28 and 36. A bromonium ion initiated highly stereocontrolled intramolecular etherification in 28 and 37 led to the tricyclic ethers 29 and 38, respectively. Reductive removal of bromine from 29 and 38 followed by RuO4 oxidation led to the furo-furanone derivatives 31 and 40, the C-5-epi ABC ring systems of the schisandra nortriterpenoids 1 and 2.本研究开发了一种立体可控的合成策略，用于构建米仔兰内酯A（micrandilactone A）与兰西多内酯G（lancifodilactone G）的ABC环系。该合成路线通过对由已知d-甘露醇衍生的不饱和酯12制得的二烯醇14进行环复分解反应（Ring-Closing Metathesis，RCM），得到对映纯的官能团化环庚烯衍生物17。在将环庚烯衍生物17转化为环庚酮20的过程中，观察到了显著的硼氢化区域选择性。对由20立体选择性制得的二烯24进行环复分解反应，得到螺环二氢呋喃25。随后将25中的缩酮单元转化为醇类化合物28与36。溴鎓离子引发的28与37中高度立体可控的分子内醚化反应，分别得到三环醚29与38。对29与38进行还原性脱溴后，经四氧化钌（RuO₄）氧化，得到呋喃并呋喃酮衍生物31与40，即五味子降三萜（schisandra nortriterpenoids）天然产物1与2的C-5差向异构体形式的ABC环系。