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

本项目旨在通过立体选择性环加成反应有效地制备天然α生育酚。1.作为初步研究，以异丁醛二硫缩醛为原料，通过卡宾加成反应，成功地合成了一种含有乙烯硫化物结构的伯醇。2.上述醇与水杨醛通过酸催化环合反应得到了新的三环1，4-氧杂硫烷。3.以邻苯二甲酸甲酯为原料，通过明智的反应和硫代缩醛反应，合成了一种用于构筑B/C环和萜类侧链的硫化物化合物。4.萜类硫化物和水杨醛之间的环化反应以较低的产率得到了三环化合物。取代的环己醇与水杨醛发生类似的反应，得到相应的四环化合物。通过硅基化合物的作用，成功地实现了杂环的还原开环反应，并一步合成了双环色满。α协议是从A环2位含羟基的四环化合物中得到的。α协议转化为包括α-生育酚在内的各种生育酚已为人所知，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.