Epipodophyllotoxin β-D-glucopyranoside (XIII), 4'-demethylepipodophyllotoxin β-D-glucopyranoside (XV), and 4'-demethylepipodophyllotoxin β-D-galactopyranoside (XVI) react with aldehydes and ketones in the presence of acid catalysts to yield the corresponding cyclic acetals and ketals. A number of 4'-demethylepipodophyllotoxin β-D-glucopyranoside derivatives exhibit a high cytostatic activity in vitro (P-815 mastocytoma cell culture) and give significant survival time increases in the mouse leukemia L-1210. Podophyllotoxin (I) and some other structurally closely related lignans and lignan glycosides isolated from the roots and rhizomes of the American Podophyllum peltatum L. and the Indian species P. emodi Wall. exert a powerful and specific inhibition of mitosis but failed to act satisfactorily in clinical trials due to nonspecific toxic side effects. Systematic chemical modification of the podophyllotoxin molecule led to several therapeutically useful semisynthetic preparations. A new glycosidation procedure was developed for the hitherto unknown glycosides of the epipodophyllotoxin type, enabling stereoselective synthesis of epipodophyllotoxin β-D-glucopyranoside and its 4'-demethyl derivatives. The condensation reaction of these glycosides with carbonyl compounds (aldehydes/ketones) generally took place with the OH groups at C-4 and C-6 of the hexapyranose moiety, and aldehydes formed two stereoisomers differing in the configuration at the newly introduced asymmetric carbon. The synthesized derivatives showed notable cytostatic activity in vitro and in vivo.