AIMTo find derivatives of p-methyl-goniotriol with more potent antitumor activities and lacking undesirable effects.

METHODSEighty derivatives of p-methyl-goniotriol have been synthesized in nine steps from alpha-D-glucoheptonic-delta-lactone (2). Compound 2 reacted with acetone in the catalyzer, H2SO4 and anhydrous MgSO4, and then reacted with 60% aqua HOAc, finally was oxidized by NaIO4 at room temperature into aldehyde 3 in a yield of 71.3%. The aldehyde 3 reacted immediately with P-CH3-PhMgBr giving mixture 4. The mixture 4 was oxidized by NaIO4, reacted with Ph3P = CHCO2Et and then induced by catalyzer. 1,8-Diazabicylclo[5, 4, 0]undec-7-ene in THF providing the compounds 6 and 7. The esterfication of 6 with cinnamyl chloride et al in 4-dimethylaminopyridine, Et3N gave the esters 8a-h. Acid hydrolysis of the acetone protecting group of 8a-h in 75% aqua HOAc gave compounds 9a-h. Their chemical structures were confirmed by IR, 1HNMR, MS and element analysis. The antitumor activities of the compounds were screened by MTT methods.

RESULTSFifteen derivatives of p-methyl-goniotriol (7, 8b-h, 9b-h) are new compounds.

CONCLUSIONPharmacological tests indicate that these compounds showed antitumor activities toward tumor cells (A2780, HCT-8, Bel742, KB) in vitro. The antitumor activities of 8b, 8d, 8g and 9h were more potent than howiinol A.