Development of Effective Preparation of Natural α-Tocopherol via Stereoselective Cycloaddition Reaction

本课题以异丁醛二硫代缩醛为原料，通过卡宾加成反应合成了一种含乙烯硫醚结构的伯醇，并与水杨醛反应合成了一种新的三环1，3.以植物内酯为原料，通过Witting反应和硫缩醛化反应，合成了一种用于构建B/C环和萜类侧链的硫醚化合物; 4.萜类硫醚与水杨醛环合，以中等产率合成了一种三环化合物。取代的环己醇代替无环的环己醇与水杨醛之间的类似反应提供相应的四环化合物。5.在硅基化合物的作用下，成功地实现了杂环化合物的还原开环反应，一步合成了双环苯并二氢吡喃。以A环2位含羟基的四环化合物为原料，合成了α-母育酚。α-母育酚转化为包括α-生育酚在内的各种生育酚是已知的，上述合成意味着生育酚的正式全合成。

This Project was undertaken to develop an effective preparation of natural α-tocopherol via stereoselective cycloaddition reaction.1.As a preliminary examination, synthesis of a primary alcohol containing vinyl sulfide structure was studied and this was successfully obtaind from isobutanal dithioacetal via carbene addition.2.The reaction of the above mentioned alcohol with salicylaldehyde afforded a new tricyclic 1,4-oxathiane by acid catalyzed cyclization.3.An sulfide compound for the construction of B/C rings and terpenoid side chain was prepared form phytone via witting reaction and thioacetalization.4.The cyclization between the terpenoid sulfide and salicylaldehyde afforded a tricyclic compound in a moderate yield. A similar reaction between substituted cyclohexanol instead of acyclic one with salicylaldehyde provided the corresponding tetracyclic compound. The both reactions proceeded with full retention of stereochemistry.5.Reductive ring opening reaction of the heterocycles thus obtained was successfully achieved by the action of a silyl compound, and bicyclic chromans were obtained in a single step. α-tocol was obtained from the tetracyclic compound containing hydroxyl group at the 2 position of the A ring. The conversion of α-tocol into various tocopherols including α-tocopherol has been known, the above synthesis means a formal total synthesis of tocopherols.