US 12,492,220 B2
Method for the preparation of oligonucleotides
Masad Damha, Montreal (CA); Tomislav Friscic, Verdun (CA); Daniel O'Reilly, Hants (GB); and James Thorpe, Montreal (CA)
Assigned to THE ROYAL INSTITUTION FOR THE ADVANCEMENT OF LEARNING/MCGILL UNIVERSITY, Montreal (CA)
Appl. No. 17/433,460
Filed by THE ROYAL INSTITUTION FOR THE ADVANCEMENT OF LEARNING/MCGILL UNIVERSITY, Montreal (CA)
PCT Filed May 26, 2021, PCT No. PCT/CA2021/050714
§ 371(c)(1), (2) Date Aug. 24, 2021,
PCT Pub. No. WO2021/243443, PCT Pub. Date Dec. 9, 2021.
Claims priority of provisional application 63/033,252, filed on Jun. 2, 2020.
Prior Publication US 2023/0192751 A1, Jun. 22, 2023
Int. Cl. C07H 21/00 (2006.01); C07H 1/00 (2006.01)
CPC C07H 21/00 (2013.01) [C07H 1/00 (2013.01)] 20 Claims
 
1. A process for synthesizing an oligonucleotide of Formula 3,

OG Complex Work Unit Chemistry
comprising reacting the nucleic acid of Formula 1,

OG Complex Work Unit Chemistry
with the nucleic acid of Formula 2,

OG Complex Work Unit Chemistry
in the presence of an activator and a sulfur transfer reagent having an SR3 moiety, and using mechanochemistry or mechanical activation to induce chemical reaction between the reagents;
wherein
n is an integer from 0 to 20;
m is an integer from 0 to 20;
R1 is a 5′ protecting group;
R2 is a 3′ protecting group;
R3 is CH2CH2CN, phenyl, chlorophenyl, or alkyl;
R7 is H, F, Ome, O-methoxyethyl, or’ in either the ribose or arabinose configuration and wherein R′ is a 2′ protecting group;
B is a nitrogen-containing base;
and R1, R2, R3, R7, and B can be the same or different in each nucleotide in the oligonucleotide.