No abstract

No abstract

On reaction of thionyl chloride with cytidine and adenosine in refluxing acetonitrile, the 5' -chloro-2',3' -sulphinyl derivatives I and VII are formed in a quantitative yield. On heating in dimethyl-formamide, compound I affords 5' -chloro-5' -deoxycyclocytidine (II) which is hydrolyzed in alkali to the arabinosyl derivative III; reduction of III with tributyltin hydride gives the 5' -deoxyarabinosyl derivative IV. The sulphinyl derivative I is hydrolyzed to 5' -chloro-5' -deoxycytidine (V) which is reduced to 5' -deoxycytidine (VI). Analogously, the sulphinyl derivative VII affords 5' -chloro-5' -deoxyadenosine (VIII) and the reduction of VIII gives 5' -deoxyadenosine (IX). Of these compounds, the 5' -chloro-5' -deoxyarabinosyl derivative as the only one shows an inhibitory effect towards the L1210 cell growth.

Enzymatic deamination of derivatives of arabinosylcytosine by partially purified cytidine deaminase isolated from mouse kidney is studied. The rate of deamination of 5'-chloroarabinosylcytosine (Ia), 5'-bromoarabinosylcytosine (Ib), 5'-chlorocyclocytidine (II), and 2',5'-anhydroarabinosylcytosine (III) is compared with that of arabinosylcytosine, of its N4-acetyl-, tri-O-acetyl-, tetraacetyl derivatives and of cyclocytidine. The deamination of the anhydro derivative III to the corresponding uracil derivative IV proceeds significantly slower than that of arabinosylcytosine, and comparably to that of cyclocytidine. The deamination of the 5'-halogeno derivatives Ia, Ib and II proceeds via the anhydro derivative III to IV. Some of the known arabinosylcytosine derivatives, cyclocytidine, N4-acetyl-, tetraacetyl- and tri-O-acetyl derivatives, show a resistance to enzymatic deamination. Different nucleoside analogs are tested as inhibitors of deaminase; only 2-β-D-ribofuranosyl-1,2,4-triazol-3-one possesses some activity.

No abstract