Studies on lignan lactone antitumor agents. II Synthesis of N-alkylamino- and 2,6-dideoxy-2-aminoglycosidic lignan variants related to podophyllotoxin.

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Abstract
D-(and L-)2,6-Dideoxy-2-aminoglycoside variants of 4''-O-demethyl-1-epipodophyllotoxin were synthesized by glycosidation of 4''-O-benzyloxycarbonyl- or 4''-O-chloroacetyl-4''-O-demethyl-1-epipodophyllotoxin (6 or 14) with the corresponding aminosugar derivatives. 1-O-(2-Amino-2-deoxy-4:6-O-ethylidene-.beta.-D-glucopyranosyl)-4''-O-demethyl-1-epipodophyllotxin (18) reacted with aldehydes in the presence of sodium cyanoborohydride, or reacted with .alpha.,.beta.-unsaturated esters, or with .alpha.,.beta.-unsaturated nitriles to yield the corresponding N-alkyl analogs. A number of the 4''-O-demethyl-1-epipodophyllotoxin .beta.-D-aminoglycoside derivatives gave significant survival time increases in mice with leukemia L-1210. In particular, 1-O-(2-dimethylamino-2-deoxy-4:6-O-ethylidene-.beta.-D-glucopyranosyl)-4''-O-demethyl-1-epipodophyllotoxin (19) showed superior activity to VP-16-213 (etoposide, 1).