Synthesis of nucleosides analogues substituted with oxy amino acetylenic derivatives

Abstract EN

This work describes the synthesis of 5-(5'-(4-disubstituted amino-butyn-2-yl) oxy -β –D-ribofuranose) uracil.

For the synthesis of these compounds, 5-(b-D-ribofuranose) uracil was converted to its 5-(2’, 3’-O-isopropylidene-β-D-ribofuranose) uracil (1), it contains the free hydroxyl group at C-5 for the required chemical modification.

Accordingly (1) was prepared from 5-(β-D ribofuranose) uracil and acetone using anhydrous ferric chloride (FeCl3) as Lewis acid catalyst.

The treatment of (1) with propargyl bromide in benzene in a phase transfer conditions in presence of tetra butyl ammonium bromide and 2% sodium hydroxide solution yielded acetylenic ether derivative 5-(2',3'-O-isopropylidene-5'-(propyn-2-yl) oxy-b-D-ribofuranose) uracil (2), which was subjected to Munich reaction with secondary aliphatic amines and par formaldehyde to give the acetylenic amino oxy derivatives (3a-f).

The treatment of (3a-f) with sulfuric acid at room temperature affected selectively the removal of acetal group at 2', 3’-position giving (4a-f) in good yield.

The aim of the present work is the preparation of new carbohydrate derivatives containing acetylenic amines soluble in water, which possess a possible biological activity