Application of Highly Stereocontrolled Glycosidations Employing 2,6-Anhydro-2-thio Sugars to the Syntheses of Erythromycin A and Olivomycin A Trisaccharide

The highly efficient syntheses of the erythromycin A (1) from its aglycon, (9S)-9-dihydroerythronolide A (4), and the C-D-E trisaccharide 3 of olivomycin A have been accomplished by the successful application of stereocontrolled glycosidations using 2,6-anhydro-2-thio sugars. The former synthesis includes the highly α-stereoselective glycosidation of the C5 desosaminated lactone 12 with phenyl 2,6-anhydro-4-O-benzyl-3-C-methyl-3-O-methyl-1,2-dithio-L-altropyranoside (10), which was achieved by using NIS-TfOH. The latter synthesis involves both the highly β-stereoselective glycosidation of 1,3-di-O-acetyl-2,6-anhydro-4-O-benzyl-2-thio-β-D-altropyranose (23), which was realized by employing TMSOTf, and the highly α-stereoselective glycosidation of phenyl 2,6-anhydro-3-O-(diethylisopropylsilyl)-4-O-isobutyryl-3-C-methyl-1,2-dithio-L-manno-pyranoside (24), which succeeded by utilizing NBS. Hydrogenolyses using Raney Ni as a catalyst and selective deprotections of the key glyco substances 17 and 22 led to the total syntheses of erythromycin A (1) and the C-D-E trisaccharide 3 of olivomycin A, respectively.