Aminolysis and alkaline hydrolysis of protected 1-hydroxybenzo-triazol-1-yl esters of adenosine 5′-phosphorothioate and -phosphorodithioate

Abstract

When 2′,3′-bis-O-(methoxyacetyl)-6-N-(9-phenylxanthen-9-yl)adenosine 9, which was prepared from adenosine in six steps and in ∼ 70% overall yield, was treated with putative tri(benzotriazol-1-yl) phosphorothioate 11 and the products then worked up with aq. triethylamine, the triethylammonium salt of die protected benzotriazol-1-yl ester 6a of adenosine 5′-phosphorothioate was obtained in high yield. The corresponding adenosine 5′-phosphorodithioate derivative 6b was prepared, also in high yield, by a modification of the latter procedure involving work-up with hydrogen sulfide and triethylamine. Reaction between die phosphorothioate derivative 6a and methylamine or morpholine gave the phosphorothioamidates 12a and 13a, respectively, to high yields; in the same way, the phosphorodithioate derivative 6b was converted into the phosphorodithioamidates 12b and 13b. Treatment of the phosphorothioate derivative 6a first with aq. alkali and then with aq. acid gave a mixture of adenosine 5′-phosphorothioate 15a and adenosine 3′,5′-cyclic phosphorothioate 17a. When the phosphorodithioate derivative 6b was treated in the same way, adenosine 3′,5′-cyclic phosphorodithioate 17b was obtained in good yield.