US 12,065,461 B2
Method for preparing 3′-O-amino-2′-deoxyribonucleoside-5′-triphosphate
Ivo Sarac, Paris (FR); and Marcel Hollenstein, Paris (FR)
Assigned to DNA Script, Le Kremlin-Bicêtre (FR); Institut Pasteur, Paris (FR); and Centre National de la Recherche Scientifique, Paris (FR)
Appl. No. 17/270,409
Filed by DNA Script, Le Kremlin-Bicêtre (FR); Institut Pasteur, Paris (FR); and Centre National de la Recherche Scientifique, Paris (FR)
PCT Filed Aug. 29, 2019, PCT No. PCT/EP2019/073135
§ 371(c)(1), (2) Date Feb. 22, 2021,
PCT Pub. No. WO2020/043846, PCT Pub. Date Mar. 5, 2020.
Claims priority of application No. 18306151 (EP), filed on Aug. 31, 2018.
Prior Publication US 2021/0214382 A1, Jul. 15, 2021
Int. Cl. C07H 1/04 (2006.01); C07H 21/04 (2006.01)
CPC C07H 1/04 (2013.01) [C07H 21/04 (2013.01)] 13 Claims
 
1. A method for preparing 3′-O-amino-2′-deoxyribonucleoside-5′-triphosphate, said method comprising the steps of:
(a) protecting 5′-hydroxy group of a 2′-deoxyribonucleoside;
(b) converting (S)-3′-hydroxy group of the compound obtained in step (a) into (R)-3′-hydroxy group;
(c) grafting the compound obtained in step (b) on a solid support functionalized with at least one N-hydroxyphthalimide moiety, wherein said at least one N-hydroxyphthalimide moiety is represented by formula (I):

OG Complex Work Unit Chemistry
wherein L represents a linker, under conditions allowing (R)-3′-hydroxy group of the compound obtained in step (b) to be substituted by a N-hydroxyphthalimide moiety of the functionalized solid support;
(d) deprotecting 5′-hydroxy group of the compound obtained in step (c);
(e) triphosphorylating 5′-hydroxy group of the compound obtained in step (d);
(f) reacting the compound obtained in step (e) with a cleaving reagent selected from the group consisting of primary amines, hydrazine and hydroxides; and,
(g) optionally recovering 3′-O-amino-2′-deoxyribonucleoside-5′-triphosphate obtained in step (f).