4-bromo-4'-demethylepipodophyllotoxin derivatives

Abstract

Preparation of 4-bromo-4'-demethylepipodophyllotoxin by reacting podophyllotoxin with hydrogen bromide at about -20.degree. C. New antitumor compounds of the formula: ##STR1## wherein R is A--(CH.sub.2).sub.n [A(CH.sub.2).sub.n ].sub.m (CHAH).sub.p --Q or ##STR2## each A, independently, is O, S, SO or SO.sub.2 ; n is an integer from 1 to 6, except when n and p, taken together, are zero, then n is 2 to 6; n is 0, 1, or 2; p is 0, 1, or 2; Q is H, alkyl from 1 to 6 carbon atoms which may be substituted with an NR.sub.1 R.sub.2 group wherein each R.sub.1 and R.sub.2, independently, is selected from the group of H, alkyl containing 1 to 6 carbon atoms which may be substituted with OH, alkanoyl containing 1 to 6 carbon atoms, or R.sub.1 and R.sub.2 are interconnected and together with the N to which they are connected form an N heterocyclic ring of 5 to 6 carbon atoms; R.sub.3 is hydrogen, and R.sub.4 is an alkyl, alkenyl, cycloalkyl, 2-furyl, 2-thienyl, aryl, aralkyl, and aralkenyl, wherein the aromatic ring may optionally be substituted, preferentially by one or more of hydroxyl, alkyl, alkoxy, nitro, or halogen radicals. R.sub.3 and R.sub.4 together with the carbon atom to which they are attached may form a saturated cycloaliphatic ring having 5 or 6 carbon atoms; each X and Y, individually, is OH or NR.sub.6 R.sub.7 wherein R.sub.6 and R.sub.7, independently, is H, alkyl containing 1 to 6 carbon atoms or one of R.sub.6 and R.sub.7 is acyl; and Z is ##STR3## Novel process for the preparation of the novel compounds or analogs thereof having advantageous stereoselection using alkyltin thiolates, preferably with selected solvents.