The total synthesis of apop-tolidin A is described employing an early glycosylation strategy.Strategic disconnections were chosen between C11-C12 (cross-coupling) and C19O-C1 (macrocyclization).The as-selective glycosylation at C9-OH was achieved with the new SIBA protective group at O2/O3 of the L-glucose residue.Auxili-ary substitutents at the 2-position of the 2-deoxy sugars were applied to form selectively the glycosidic linkages of the C27 disaccharide.The cross-cou-pling of the glycosylated northern half with the glycosylated southern half was achieved with Cu~I-thiophene carboxy-late.The macrocyclization of a trihy-droxy carboxylic acid produced the 20-membered macrolide selectively.H_2SiF_6 was suitable for the final depro-tection of the silyl ethers and the con-version of the C21 methylketal into the hemiketal.The synthetic flexibility of the approach was proven by the syn-thesis of some glycovariants.
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