The Preparation and Properties of 5-Methyltetrahydrofolic Acid and its Analogues

Abstract

A simple method of preparation of 5 Methyltetrahydrofolic acid has been devised. This material is known to be the major folate present in natural materials and is involved in many biochemical reactions necessary for maintaining life. The calcium and barium salts were prepared and the chemical and physical properties studied. Nuclear Magnetic Resonance and Ultraviolet Spectrometry confirmed its identity and purity. It was shown by E.S.R. to exist as a free radical in the solid state. Microbiological Assay showed it was free from other folates. The higher analogues, ethyl, propyl and butyl were also prepared and identified by the above techniques. The toxicity and tumour inhibitory properties of the calcium salts were investigated and showed that they were non toxic and of possible use as tumour inhibitors. 5 Methyltetrahydrofolic acid was shown to effectively reverse the toxicity of methotrexate in the treatment of solid tumours. The 5 Methyl and 5 Ethyl derivatives of tetrahydromethotrexate were also prepared, purified and identified. The Ultraviolet and Nuclear Magnetic Resonance Spectra were compared with those of the folate series. Trials on their toxicity and tumour inhibitory properties were conducted. The overall advantage of this method for the production of folate derivatives is that they can be prepared, quickly and cheaply in large quantities without the isolation of intermediates. However, unsuccessful attempts were made to prepare the 5 isopropyl, the 5 benzyl and 5 [please see Thesis] phenyl ethyl derivatives of tetrahydrofolic acid and also 5 methyltetrahydropteridine.