Total synthesis and structure determination of plakortones

研究了丙曲酮C和丙曲酮F的全合成。Evans手性助剂丙酸酯经烷基化脱除后，羧酸转化为相应的二甲基酰胺，并进行碘代丙酮化反应。非对映选择性得到的内酯被还原为二醇，其伯醇被保护为三烷基醚。在几个步骤中得到的酮作为烷基烷的前驱体与三甲基硅基重氮甲烷反应得到二氢呋喃。烯丙基氧化，然后DIBAL还原得到乳氨酸，用ph_3chco_20亿处理。所得饱和酯为非对映体混合物，它们是可分离的，每个对映体都可以用DBU对映。酯的水解，然后碘内顿化和随后的自由基还原得到具有所需核心部分的内酯醛。经一碳延伸后，醛进行Wittig反应得到αβ-不饱和酯。用DIBAL将酯和内酯还原为乳醇。乳酸受到保护，乙醇被氧化为醛，醛被暴露于脱羧选择性乙基化。乙醇的邻乙酸酯的消去和Claisen重排得到的酯被还原为烃。乳酸部分的氧化产生了最终的化合物。合成化合物的核磁共振波谱与天然化合物的核磁共振波谱不相同，其中天然产物一定是其非对映体。天然产物的合成将以与本研究中建立的哑巴相似的方式完成。

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.