Improved preparation of 2,3:5,6:3′,4′-tri-O-isopropylidenelactose dimethyl acetal and its 6′-O-(1-methoxy-1-methylethyl) derivative

Efficient preparations both of 2,3:5,6:3′,4′-tri-O-isopropylidenelactose dimethyl acetal (5, 95% yield) and its 6′-O-(1-methoxy-1-methylethyl) derivative (65% yield), useful intermediates for the conversion of lactose into biologically relevant oligosaccharides, by ‘one-pot’ acetonation procedures with 2,2-dimethoxypropane are reported. The acetonation of 5 with 2-methoxypropene in the presence of pyridinium tosylate and 4 Å molecular sieves unexpectedly revealed the formation, in a first kinetic reaction phase, of similar amounts of the 2′-O- and 6′-O-(1-methoxy-1-methylethyl) acetals. The structures of all new products were fully characterized by NMR analyses, which also allowed some deductions on the conformation of the galactopyranosyl rings.