α-1-tributyltin-O-2,3-bisacetyl-4,6-ethylidene-glucose as a convenient glycosidation reagent: An efficient synthesis of etoposide

Article abstract of DOI:10.1016/0040-4020(95)01122-6

The antineoplastic drug etoposide has been prepared by a chemically and operationally simple process. The salient reaction is the BF₃.etherate promoted, room temperature condensation of 4'-demethyl-4'-acetyl-epipodophyllotoxin 4, with α-1-Bu₃Sn-O-2,3-bisacetyl-4,6-ethylidene-glucose 6. The latter compound was prepared from 4,6-β-ethylidene glucose triacetate and Bu₃Sn-OMe obtained in situ from (Bu₃Sn)₂O and dimethyl carbonate. A readily separable mixture of α and β-etoposide triacetate epimers was obtained where the desired β-epimer predominated. In contrast, 4,6-α-ethylidene glucose diacetate and 4, even at 0°C, gave an equimolar mixture of epimers. It is proposed that the stereochemical outcome may be attributed to electronic effects in the activated tin-glucose reagent.