Synthesis of the subterminally 6-O-phosphorylated trimannosides found on carbohydrate chains of lysosomal enzymes

The three possible subterminally 6-O-phosphorylated trimannosides (2–4) found on the asparagine-linked carbohydrate chains of lysosomal enzymes have been chemically synthesized as their 8-methoxycarbonyloctyl glycosides, R = (CH2)8COOCH3. The key step in the syntheses involves glycosylation of suitably protected α-D-mannopyranosides 5–7 with the phosphorylated mannobiosyl donor 2-O-(2,3,4,6-tetra-O-acetyl-α-D-mannopyranosyl)-3,4-di-O-benzyl-6-O-di-phenylphosphoryl-α-D-mannopyranosyl chloride (14), which produced mixtures of α- and β-linked trisaccharidic products. Compounds 2 (αDMan(1 → 2) αDMan 6-phosphate(1 → 2)αDManOR), 3 (αDMan(1 → 2)αDMan 6-phosphate(1 → 3)αDManOR), and 4 (αDMan(1 → 2)αDMan 6-phosphate(1 → 6)αDManOR) are being used in a study of the targeting of enzymes to the lysosomes by phosphomannosyl receptors.