Construction of Chiral Building Blocks through Enantioselective Protonation

我们以前成功地制备了一个手性结构单元，（S）-3-（4 γ-丁内酯）-丙酸（1），通过对映选择性质子化与（1 S）-10-乙酰基-磺酸上的4-羟基庚二酸二钠。从长根奥德蘑（Oudemansiellaradicata）中分离得到光学活性的乌地酮。乌地酮对自发性高血压大鼠有明显的降压作用，其机制可能与抑制酪氨酸羟化酶有关。1经两步还原得到（S）-4-庚烷并与幻甲基反应生成甲基氧鎓。甲基氧鎓与1，3-戊二酮的双酯反应得到光学活性的乌地酮。利用手性结构单元1合成了4-己内酯、依丹酮、4-十二烷酮等信息素，通过加成-消除反应合成了手性六元内酯，成功地合成了光学活性的罗汉果酸。由于罗汉果酸已被转化为六个二萜类化合物，包括紫杉二酮，已被声称具有抗肿瘤活性，罗汉果酸的手性合成构成了这六个二萜类化合物的光学活性形式的正式全合成。

We had previously succeeded in preparing a chiral building block, (S)-3-(4gamma-butyrolactone)-propionic acid (1), by an enantioselective protonation with (1S)-10-camphor-sulfonic acid onto disodium 4-hydroxypimelate. Optically active oudenone, isolated from Oudemansiella radicata, was synthesized from 1. Oudenone has significant hypotensive activity against spontaneously hypertensive rats due to inhibitions of tyrosine hydroxylase. Two-step reduction of 1 afforded (S)-4-heptanolide, which was transformed into a methyloxonium species by the reaction with magic methyl. Reaction of the methyloxonium species with an enorate of 1,3-pentane-dione gave optically active oudenone. A chiral building block 1 was utilized for the syntheses of pheromones such as 4-hexanolide, eldanolide, 4-dodecanolide.Another chiral 6-membered lactone prepared through addition-elimination process was successfully used for the chiral synthesis of optically active podocarpic acid. Since podocarpic acid has been converted into six diterpenoids including taxodione, which has been claimed to possess anti-tumor activity, chiral synthesis of podocarpic acid constitutes a formal total synthesis of these six diterpenoids in optically active form.