Glycosidation, VII. Development of Selective Cytostatica for Cancer Therapy Synthesis of Acetal‐β‐glucosides from Cytotoxic Aldehydes

Aldehydes are highly cytotoxic compounds, but they can normally not be used in cancer therapy because of fast binding to serum proteins. However, they could be transformed into acetal‐β‐glucosides 5, a nontoxic transport form, from which they can be freed by enzymatic or acid‐catalyzed hydrolysis. The acetyl‐protected acetal‐β‐glucosides 4 are obtained in excellent yield and highly selectively by reaction of trimethylsilyl 2,3,4,6‐tetra‐O‐acetyl‐β‐D‐glucopyranoside (1c) and an acetal 2 in the presence of catalytic amounts of trimethylsilyl trifluoromethanesulfonate (3) in dichloromethane at −70°C. Deacetylation gives the free acetal‐β‐glucosides 5. Similarly, trimethylsilyl 2,3,4,6‐tetra‐O‐benzyl‐β‐glucopyranoside (1e) was used to afford the benzyl‐protected acetal‐β‐glucosides 6. The formation of 4 or 6 can also be achieved by reaction of 1c or 1e with an aldehyde 8 and an alkyl trimethylsilyl ether 7 in the presence of 3.