Tosyl Derivatives Research Articles

Analogs of Tetrahydrofolic Acid XIV: Facile Synthetic Route to the 2-Amino-5-(3-anilinopropyl)-6-methyl-4-pyrimidinol Type of Folic Reductase and Thymidylate Synthetase Inhibitor

A four-step synthesis of the title compound (X b ) from p -tolylsulfonanilide has been described which proceeds in 35 per cent over-all yield via ethyl 2-acetyl-5-( N -tosylanilino)valerate (IV b ) and the N -tosyl derivative of X b (VII b ). That this synthetic route had considerable generality was shown with four other examples—namely, 2-amino-6-methyl-5-( p -nitroanilinopropyl)-4-pyrimidinol (X c ), 2-amino-5-( p -carbethoxyanilinopropyl)-6-methyl-4-pyrimidinol (X d ), 2-amino-5-(3-anilinopropyl)-6-benzyl-4-pyridiminol (XVII b ), and 2-amino-5-(3-anilinopropyl)-6-phenyl-4-pyrimidinol (XVII a ). XVII a and b were good inhibitors of rat liver folic reductase, being complexed five and two times better, respectively, than the substrate, folic acid. Since XVII a and b are 35 and 16 times better, respectively, than the 6-methylpyrimidine (X b ), the phenyl ring at the 6-position is probably an additional point of binding to the enzyme.

THE STRUCTURE AND PROPERTIES OF DL-1,2-O-CYCLOHEXYLIDENEGLYCEROL

DL-1,2-O-Cyclohexylideneglycerol was prepared by reacting cyclohexanone and glycerol in the presence of sulphuric acid. It is miscible with all common organic solvents and is slightly soluble in water. It is not affected by hydrogenolysis at 25 °C. over palladous oxide at 50 p.s.i. for 24 hr. The DL-1,2-O-cyclohexylidene-3-O-p-nitrobenzoylglycerol is readily cleaved by mineral acids to yield 3-O-p-nitrobenzoylglycerol. Proof of the 1,2 ketal structure was obtained by (a) preparation of the monomethyl derivative, acid hydrolysis, and periodic acid oxidation of the resultant 1-monomethyl ether of glycerol and (b) treatment of the tosyl derivative with sodium iodide which gave a 93% yield of sodium p-toluenesulphonate.