[Preparation, stereochemical study and evaluation of the antileukemic activity of glucoside derivatives of (-)-steganol].
The optically active lignan (-)-steganol was prepared from natural (-)-steganacin by selective deacetylation and was transformed, via a three-step sequence, into the corresponding 4', 6'-O-ethylidene- and thenylidene-beta-D-glucopyranosides, 3b and 3c, respectively, which are the analogues, in the steganol series, of the podophyllotoxin derived, and clinically useful, anticancer drugs, VP16-213 and VM26. Formation of the dimeric compound distegyl ether as a minor by-product was established. Complete elucidation of all the asymmetric centres was performed with the help of high resolution 1H-nmr studies at 400 MHz, COSY experiment at 500 MHz and X-ray analysis. Contrary to the podophyllotoxin series, the glycosylation of (-)-steganol occurred with retention of configuration, and all the synthesized compounds, including distegyl ether, exhibited the starting natural R configuration at C-5.
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000032:analysis* / Q000138:chemical synthesis / Q000627:therapeutic use; D055598:Chemical Phenomena; D002621:Chemistry; D003640:Dealkylation; D005960:Glucosides; D007783:Lactones / Q000032:analysis; D007942:Leukemia, Experimental / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008968:Molecular Conformation; D013237:Stereoisomerism
D000972:Antineoplastic Agents, Phytogenic; D005960:Glucosides; D007783:Lactones
Preparation, etude stereochimique et evaluation de l'activite antileucemique de derives glucosidiques du (-)-steganol.