Total synthesis and structure determination of plakortones

以Evans手性助剂的丙酸酯为原料，经烷基化反应，除去手性助剂后，羧酸转化为相应的二甲酰胺，二甲酰胺再经碘内酯化反应，合成了普拉科酮C和普拉科酮F。非对映选择性获得的内酯被还原为二醇，其伯醇被保护为三苯甲基醚。在几个步骤中衍生的酮作为亚烷基卡宾的前体与锂三甲基硅基重氮甲烷反应，得到二氢呋喃。烯丙位氧化后经DIBAL还原得到内半缩醛，再用Ph_3CHCO_2Bn处理。所得饱和酯为非对映异构体的混合物，它们是可分离的，并且每个差向异构体可以用DBU差向异构化。酯的水解，随后碘内酯化和随后的自由基还原得到具有所需核心部分的内酯醛。醛经一个碳原子延伸后，经Wittig反应得到αβ-不饱和酯。用DIBAL将酯和内酯还原为内缩醛醇。内半缩醛被保护，醇被氧化成醛，醛暴露于不对称选择性乙基化。醇的邻位乙酸酯的消除和Claisen重排得到酯，酯被还原成烃。内半缩醛部分的氧化产生最终化合物。合成化合物的核磁共振谱与天然产物的核磁共振谱不一致，天然产物应是其非对映体。天然产物的合成将以与本研究中建立的方法类似的方式完成。

Total synthesis of plakortone C and F was investigated.After alkylation of the propionate of Evans' chiral auxiliary and removal of the auxiliary, the carboxylic acid was transformed to the corresponding dimethyl amide, which was subjected to iodolactonization. The lactone, obtained diastereoselctively, was reduced to the diol, whose primary alcohol was protected as a trityl ether. The ketone derived in few steps as a precursor of the alkylidenecarbene was reacted with lithiotrimethylsilyldiazomethane to give a dihydrofuran. Allylic oxidation, followed by DIBAL reduction gave a lactol, which was treated with Ph_3CHCO_2Bn. The resulting saturated ester was a mixture of diastereomers, which were separable and each epimers could be epimerized with DBU.Hydrolysis of the ester, followed by iodolactonization and subsequent radical reduction afforded lactone aldehyde with the desired core part. After one carbon elongation, the aldehyde was subjected Wittig reaction to give αβ-unsaturated ester. The ester and lactone were reduced with DIBAL to lactol alcohol. The lactol was protected and the alcohol was oxididized to aldehyde, which was exposed to the enatioselective ethylation. Elimination and Claisen rearrangement of ortho-acetate of the alcohol gave the ester which was reduced to the hydrocarbon. Oxidation of the lactol part produced the final compound. The NMR spectra of the synthetic compound and, those of the natural one were not identical, therein, the natural product must be its diastereomer. The synthesis of the natural product will be accomplished in the similar way as the mute established in this investigation.