HCID 178418361, compound → HCID 178508903, compound

HRID 1576745Notes

Reaction equation

HRID 1576745 reaction equation
[CH:1]1[C:6]([C:7]([NH:9][C@H:10]([C:16]([OH:18])=[O:17])[CH2:11][CH2:12][C:13]([OH:15])=[O:14])=[O:8])=[CH:5][CH:4]=[C:3]([NH:19][CH2:20][CH2:21][C:22]2[N:27]=[C:26]3[C:28]([N:30]=[C:31]([NH2:33])[NH:32][C:25]3=[N:24][CH:23]=2)=[O:29])[CH:2]=1.[H][H]>[Pt]=O>[CH:5]1[C:6]([C:7]([NH:9][CH:10]([C:16]([OH:18])=[O:17])[CH2:11][CH2:12][C:13]([OH:15])=[O:14])=[O:8])=[CH:1][CH:2]=[C:3]([NH:19][CH2:20][CH2:21][C@@H:22]2[NH:27][C:26]3[C:28]([OH:29])=[N:30][C:31]([NH2:33])=[N:32][C:25]=3[NH:24][CH2:23]2)[CH:4]=1

Participants

4

Reactant 2

HCID 178418361HCID 178418361, compoundHCID 178508921HCID 178508921, compound

Product 1

HCID 178508903HCID 178508903, compound

Reagents, catalysts & solvents 1

HCID 82844Platinum oxide (PtO)Catalyst

Procedure

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°-10°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.

Sources & evidence

ORD record
ord-21e9bc796eb547d5b12997b3da79dc96
Source dataset
uspto-grants-1976_09
Patent number
US03983118

Reaction notes

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