[Syntheses and antitumor activities of the derivatives of P-methyl goniotriol in vitro].
OBJECTIVE
To find derivatives of p-methyl-goniotriol with more potent antitumor activities and lacking undesirable effects.


METHODS
Eighty 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.


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


CONCLUSIONS
Pharmacological 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.
Chen
Hong
H
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Chen
Ruo-yun
RY
Yu
De-quan
DQ
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000473:pathology; D006801:Humans; D007624:KB Cells; D015394:Molecular Structure; D011753:Pyrones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D011753:Pyrones