Construction of Chiral Building Blocks through Enantioselective Protonation

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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.