Structure Assignment of Lagunapyrone B by Fluorous Mixture Synthesis of Four Candidate Stereoisomers

Techniques of fluorous mixture synthesis have been used to make four candidate stereoisomers
for the natural product lagunapyrone B. A quasiracemic mixture of vinyl iodides whose component
configurations at C19−21 were encoded by fluorous silyl groups was fused to a central fragment by a
Negishi coupling. A separate quasiracemic mixture of pyrone fragments whose component configurations
at C6,7 were also encoded by fluorous silyl groups was synthesized and demixed. Stille coupling of the
resulting pure quasienantiomers with the quasiracemic mixture provided two quasi-diastereomeric samples,
which were demixed and detagged to provide all four lagunapyrone B stereoisomers. Lagunapyrone was
assigned the 6R,7S,19S,20S,21R configuration by comparison of optical rotations.

本研究采用氟代混合合成（fluorous mixture synthesis）技术，为天然产物拉格纳吡喃酮B（lagunapyrone B）制备了四组候选立体异构体（stereoisomers）。
将以氟代硅基（fluorous silyl groups）标记组分C19~C21位构型的乙烯基碘化物（vinyl iodides）准外消旋混合物（quasiracemic mixture），通过根岸偶联反应（Negishi coupling）与中心骨架片段进行拼接。
另合成一组以氟代硅基标记组分C6、C7位构型的吡喃酮片段（pyrone fragments）准外消旋混合物，并经拆分得到纯准对映异构体（quasienantiomers）。
将所得纯准对映异构体与前述准外消旋混合物进行施蒂勒偶联反应（Stille coupling），得到两组准非对映异构样品（quasi-diastereomeric samples）；随后对这两组样品分别进行拆分与脱标记处理，最终获得全部四种拉格纳吡喃酮B立体异构体。
通过比对各立体异构体的旋光度（optical rotations），确定拉格纳吡喃酮B的构型为6R,7S,19S,20S,21R。