Document Type and Number:
Japanese Patent JPS5541234
Kind Code:
B2
Abstract:
The preparation of N5-methyltetrahydrohomofolic acid and alkali metal salts thereof is from homofolic acid starting material (HFA) by catalytic reduction with platinum oxide in the dark under hydrogen at a slight overpressure to produce tetrahydrohomofolate (THHF), them immediately reacting this product with formaldehyde to produce 5,11-methylenetetrahydrohomofolate and reducing this methylene intermediate without isolation with sodium borohydride to give the desired 5-methyltetrahydrohomofolate in the disodium salt form. The 5-methyl product is recovered by precipitating side products at a pH of about 3.8 with acetic acid and refrigerating the product filtrate overnight at about 3 DEG -10 DEG C. The filtrate containing the product 5-methyltetrahydrohomofolate (5-MeTHHF) is treated with charcoal, concentrated to an oil and the 5-methyl product is precipitated with absolute ethanol. The 5,11-methylenetetrahydrofolate may be separately recovered and in a second reaction an additional product known as the 5,11-methenyl is formed by reaction with formic acid. These products show increased stability over folate analogues and show biological promise in the treatment of cancer and leukemia as antifolates and specifically against L1210-FR8 tumor in mice.
More Like This:
Application Number:
JP6736473A
Publication Date:
October 22, 1980
Filing Date:
June 16, 1973
Export Citation:
International Classes:
A61K31/505; A61K31/519; A61P35/02; C07D475/04; C07D487/14; (IPC1-7): C07D475/04