TRIBUTYLTIN-O-2,3-BISACETYL-4,6-ETHYLIDENE-GLUCOSE AS A CONVENIENT GLYCOSIDATION REAGENT - AN EFFICIENT SYNTHESIS OF ETOPOSIDE

The antineoplastic drug etoposide has been prepared by a chemically an d operationally simple process. The salient reaction is the BF3-ethera te promoted, room temperature condensation of 4'-demethyl-4'-acetyl-ep ipodophyllotoxin 4, with alpha-1-Bu(3)Sn-O-2,3-bisacetyl-4,6-ethyliden e 6. The latter compound was prepared From 4,6-beta-ethylidene glucose triacetate and Bu(3)Sn-OMe obtained in situ from (Bu(3)Sn)(2)O and di methyl carbonate. A readily separable mixture of alpha and beta-etopos ide triacetate epimers was obtained where the desired beta-epimer pred ominated. In contrast, 4,6-alpha-ethylidene glucose diacetate and 4, e ven at 0 degrees C, gave an equimolar mixture of epimers. It is propos ed that the stereochemical outcome may be attributed to electronic eff ects in the activated tin-glucose reagent.