BIOMIMETIC SYNTHESIS OF THE METABOLITES OF TREQUINSIN

Six metabolites of Trequinsin ,7-tetrahydro-2H-pyrimido[6,1-a]isoquino lin-4-one. hydrochloride] are identified which have been synthesised f rom the parent molecule trequinsin 1. A base-promoted selective demeth ylation of 1 at position 9 gives the metabolite 4. An acid aided demet hylation at position 10 furnishes the metabolite 7. Treatment of compo unds 1 and 4 with DDQ gives the 4'-DDQ complexes 10 and 14 respectivel y. These complexes on treatment with ZnCl2-MeOH afford the 4'-methoxym ethyl derivatives 11 and 15 respectively, which on subsequent demethyl ation with dil. HCl give the corresponding hydroxy derivatives 2 and 5 . When treated with two equivalents of DDQ, 1 gives the DDQ complex 12 , which on subsequent treatment with Zn(OAc)(2) yields the 4'-formyl d erivative 13. Oxidation of 13 with AgNO3-NaOH gives the 4'-carboxy der ivative 3, which was subsequently selectively demethylated to give the metabolite 6. Treatment of 13 with NH2OH.HCl produces the oxime 17, w hich is then dehydrated to the nitrile 18 using (Ac)(2)O. Alkaline hyd rolysis of 18 gives 3.