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

立体选择性环加成反应有效制备天然α-生育酚的研究进展

• 批准号: 13555252
• 负责人: INOUE Seiichi
• 金额: $ 5.7万
• 依托单位: YOKOHAMA NATIONAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13555252/
• 关键词: SALICYLALDEHYDE; VYNYL SULFIDE; 1,4-OXATHIANE; ORTHOQUINONEMETHIDE; FUSED TRICYCLES; FUSED TETRACYCLES; BIOACTIVE CHROMANES; 1, 4-オキサチアン; クロマン

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.

本课题旨在通过立体选择性环加成反应制备天然α-生育酚。作为初步考察，研究了以异丁醇二硫缩醛为原料，经加氢加成，成功地合成了含乙烯基硫化物结构的伯醇。上述醇与水杨醛反应，通过酸催化环化得到了新的三环1,4-草硫烷。以植物酮为原料，经witting反应和硫代乙酸化反应制备了用于构建B/C环和萜类侧链的硫化化合物。萜类硫化物和水杨醛之间的环化得到了一个产率中等的三环化合物。取代环己醇与水杨醛发生类似反应，得到相应的四环化合物。这两个反应都保持了完全的立体化学。在硅基化合物的作用下，成功地实现了杂环的还原开环反应，一步制得双环铬。α-tocol是由A环2位含有羟基的四环化合物得到的。α-生育酚可转化为包括α-生育酚在内的各种生育酚，上述合成是指生育酚的正式全合成。

项目成果

井上誠一, 土屋文明, 王平, 佐藤美智, 広森修平, 星野雄二郎, 本田清: "o-キノンメチドの反応性を利用した縮合三環式多環式ベンゾピラノオキサチアン及びその誘導体の合成"第46回有機合成化学協会関東支部新潟シンポジウム講演要旨集. 153-154 (2003)

Seiichi Inoue，Fumiaki Tsuchiya，Hei Oh，Yoshitomo Sato，Shuhei Hiromori，Yujiro Hoshino，Kiyoshi Honda：“利用邻醌甲基化物的反应性合成稠合三环多环苯并吡喃氧噻烷及其衍生物”第46届合成有机化学关东卷摘要。新泻支部研讨会。153-154（2003）

井上誠一: "ペリ環状反応による含酸素複素環化合物の立体選択的合成"日本化学会第80秋季年会講演予稿集. 120-120 (2001)

Seiichi Inoue：“通过周环反应立体选择性合成含氧杂环化合物”日本化学会第 80 届秋季年会论文集 120-120 (2001)。

S.Inoue: "Stereoselective Synthesis of Isoprenoids by Use of Pericyclic Reactions"Abstracts, International Symposium on the Chemistry of Essential Oils, Terpenes, and Aromatics. S6-S9 (2002)

S.Inoue：“利用周环反应立体选择性合成类异戊二烯”摘要，精油、萜烯和芳烃化学国际研讨会。

井上誠一, 土握文明, 王 平, 佐藤美智, 本田 清: "ο-キノンメチドの反応性を利用した縮合三環式ベンゾピラノオキサチアン及びその類縁体の合成"第44回有機合成化学協会関東支部新潟シンポジウム講演要旨集. 121-122 (2002)

Seiichi Inoue、Fumiaki Tsunari、Ping Wang、Yoshitomo Sato、Kiyoshi Honda：“利用邻醌甲基化物的反应性合成稠合三环苯并吡喃氧噻嗪及其类似物”第44届合成有机化学学会关东分会新泻研讨会演讲摘要121-122（ 2002）

INOUE, SEIICHI, et al.: "Single-Step Synthesis of Fused Hetero-polycyclic Compounds from Salicylaldehydes and Unsaturated Cyclic Alcohols and their Sulfur Analogs."Abstracts of 18^<th> International Congress of Heterocyclic Chemistry. 555 (2001)

INOUE、SEIICHI 等人：“从水杨醛和不饱和环醇及其硫类似物单步合成稠合杂多环化合物”。第 18 届国际杂环化学大会摘要。