A new highly diastereoselective synthesis of the polyhydroxylated pyrrolidine alkaloid (±)-codonopsinol B and its -nor-methyl analogue, starting from achiral materials, is presented. The strategy relies on the -stereoselective epoxidation of 2,3-dihydroisoxazole with in situ-generated DMDO, the -selective α-chelation-controlled addition of vinyl-MgBr/CeCl to the isoxazolidine-4,5-diol intermediate, and the substrate-directed epoxidation of the terminal double bond of the corresponding γ-amino-α,β-diol with aqueous hydrogen peroxide catalyzed by phosphotungstic heteropoly acid. Each of the key reactions proceeded with an excellent diastereoselectivity (dr > 95:5). (±)-Codonopsinol B was prepared in 10 steps with overall 8.4% yield. The antiproliferative effect of (±)-codonopsinol B and its -nor-methyl analogue was evaluated using several cell line models.
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