Apoptolidinone A: synthesis of the apoptolidin A aglycone.

摘要: An efficient stereocontrolled synthesis of apoptolidinone A, the aglycone apoptolidin A is described. The synthetic strategy relies on a cross coupling between C11/C12 northern half (C1–C11) and southern part (C12–C28) followed by ring-size selective macrolactonization. Key steps for introduction stereocenters are stereoselective aldol reaction, substrate controlled dihydroxylation chelation-controlled Grignard/aldehyde addition. conjugated triene was built up successively E-selective Wittig reactions. L-Malic acid chosen as chiral pool source C8/C9 stereocenters. final cleavage silyl ethers conversion C21 methyl ketal into hemiketal achieved HF⋅pyridine.