Reaction of mannopeptimycin-alpha (I) with 6-methoxy-2-naphthaldehyde dimethyl acetal (II) under acidic conditions leads to a mixture of regioisomeric naphthylmethylidene acetals (III) and (IV) on the terminal mannose moiety (1-3).
Reductive ring opening of the mixture of acetals (III) and (IV) by means of NaBH3CN and trifluoroacetic acid produces the corresponding mixture of 2-, 3-, 4- and 6-O-naphthylmethyl ethers, from which the target 4-O-ether is isolated by preparative HPLC (1-3).