The preparation of 6‐ and 7‐(pX‐phenyl)‐4(3H)‐pteridinones (X = H, CH3, OCH3) is described. The oxidation of these compounds by (immobilized) Arthrobacter M‐4 cells containing xanthine oxidase has been studied. The oxidation monitored by uv spectroscopy usually goes fast, except for 7‐(pX‐phenyl)‐4(3H)‐pteridinones (X = CH3, OCH3), which are slowly oxidized. With bacterial cells immobilized in gelatine crosslinked with glutaraldehyde small laboratory‐scale oxidations were carried out. Based on spectral data the products of the oxidation reactions are 6‐ and 7‐aryllumazines.
Synthetic routes for the preparation of 3‐alkyl‐6‐phenyl‐4(3H)‐pteridinones 6 and their corresponding 8‐oxides 5 (R = CH3, C2H5, (CH2)2CH3, (CH2)3CH3, CH(CH3)C2H5, CH(CH3)2 and CH(C2H5)CH2OCH(OC2H5)2 are described and their reactivities towards xanthine oxidase from Arthrobacter M‐4 are determined. Only the 3‐methyl derivative of 6‐phenyl‐4(3H)‐pteridinone and its 8‐oxide i. e. 6a and 5a are found to be substrates although their reactivities are still very low. Oxidation takes place at C‐2 of the pteridinone nucleus. All the 3‐alkyl derivatives are less tightly bound to the enzyme than 6‐phenyl‐4(3H)‐pteridinone. Introduction of the N‐oxide at N‐8 considerably lowers the binding of the substrates. Inhibition studies have revealed that 3‐methyl‐6‐phenyl‐4(3H)‐pteridinone (6a) is a non‐competitive inhibitor with a Ki‐value of 47 μM and the 3‐ethyl derivative (6b) an uncompetitive one with a Ki‐value of 19.6 μM.
7‐Phenyl‐, 7‐(p‐methoxyphenyl)‐, 7‐methyl‐, 7‐t‐butyl‐, 6,7‐diphenyl‐, 6,7‐dimethyl‐ and 2‐phenylpteridine are converted in good yields into their respective 4‐amino compounds, when they are dissolved in liquid ammonia (‐40°) and potassium permanganate is added to the solution. Increase of the temperature of the amino‐oxidation did not change the position of substitution, the yields are however lower. The intermediary of 4‐aminodihydropteridines in these reactions has been proved by 1H nmr spectroscopy.
Aus den substituierten Pteridinen (I) erhält man bei der Oxidation in flüssigem Ammoniak über die Derivate (II) die Aminierungsprodukte (III), die z.Tl. salzsauer zu (IV) hydrolysiert werden.
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