Fast deprotecting n-exocyclic amino cyclic hydrocarbon protected groups for nucleoside phosphoramidites
Compounds useful for forming nucleic acids having the structure of Formula I: Each of R 1 or R 2 is independently selected from hydrogen, a protecting group, or a phosphoramidite group. R 3 is selected from H, F, O—C 1-6 alkyl, O-MOE and a removable hydroxyl-protecting group. Q is a heterocyclic base. R 4 is a cyclic hydrocarbon. Also disclosed are processes for forming the nucleic acids from the compounds and the nucleic acid products produced.
1 . A compound having the structure of Formula I:
wherein each of R 1 or R 2 is independently selected from the group consisting of a protecting group and a phosphoramidite group, provided R 1 and R 2 are not both protecting groups;
wherein R 3 is H, F, O—C 1-6 alkyl, O-MOE, or O-thiocarbon protecting group;
wherein Q is a heterocyclic base; and
wherein R 4 is cyclopentyl or cyclohexyl.
2 . The compound according to claim 1 , wherein said compound has the structure of Formula Ia:
wherein each of R 1 or R 2 is independently selected from the group consisting of a protecting group and a phosphoramidite group, provided R 1 and R 2 are not both protecting groups;
wherein R 3 is H, F, O—C 1-6 alkyl, O-MOE, or O-thiocarbon protecting group; and
wherein R 4 is cyclopentyl or cyclohexyl.
3 . The compound according to claim 2 , wherein R 1 and R 2 are each independently selected from 4,4′-dimethoxytrityl (DMT) and 2-cyanoethyl-(N,N-diisopropylamino)-phosphoramidite.
4 . The compound according to claim 3 , wherein R 4 is cyclopentyl and wherein R 3 is O-TC:
5 . The compound according to claim 1 , wherein said compound has the structure of Formula Ib:
wherein each of R 1 or R 2 is independently selected from the group consisting of a protecting group and a phosphoramidite group, provided R 1 and R 2 are not both protecting groups;
wherein R 3 is H, F, O—C 1-6 alkyl, O-MOE, or O-thiocarbon protecting group; and
wherein R 4 is cyclopentyl or cyclohexyl.
6 . The compound according to claim 5 , wherein R 1 and R 2 are each independently selected from 4,4′-dimethoxytrityl (DMT) and 2-cyanoethyl-(N,N-diisopropylamino)-phosphoramidite.
7 . The compound according to claim 6 , wherein R 4 is cyclopentyl and wherein R 3 is O-TC:
8 . A method comprising:
contacting a nucleoside residue comprising a 5′ or 3′ unprotected hydroxyl with a protected nucleotide monomer having the structure of Formula I:
wherein each of R 1 or R 2 is independently selected from the group consisting of a protecting group and a phosphoramidite group, provided R 1 and R 2 are not both protecting groups;
wherein R 3 is H, F, O—C 1-6 alkyl, O-MOE or O-thiocarbon protecting group;
wherein Q is a heterocyclic base; and
wherein R 4 is cyclopentyl or cyclohexyl,
under conditions sufficient to covalently bond said phosphoramidite group of said protected nucleotide monomer to said unprotected hydroxyl group of said nucleoside residue and produce an internucleotide bond.
9 . The method according to claim 8 , wherein said method further comprises exposing said internucleotide bond to an oxidizing agent.
10 . The method according to claim 8 , wherein said method further comprises removing said thiocarbon protecting group.
11 . The method according to claim 8 , wherein said nucleoside residue is covalently bound to a solid support.
12 . The method according to claim 11 , wherein said method further comprises cleaving said nucleic acid from said solid support to produce a free nucleic acid.
13 . The method according to claim 8 , wherein the thiocarbon protecting group is selected from the group of structures consisting of:
14 . The method according to claim 13 , wherein the thiocarbon protecting group is
and wherein each of R 1 or R 2 is independently selected from the group consisting of 4,4′-dimethoxytrityl (DMT) and 2-cyanoethyl-(N,N-diisopropylamine)-phosphoramidite.
15 . The method according to claim 14 , wherein Q is G or C.
16 . The method according to claim 15 , wherein Q is G.
17 . A protected nucleic acid comprising the structure of Formula VIII:
wherein R 3 is H, F, O—C 1-6 alkyl, O-MOE, or O-thiocarbon protecting group;
wherein Q is a heterocyclic base;
wherein R 4 is cyclopentyl or cyclohexyl;
wherein R 5 is selected from the group consisting of hydrogen, a hydrocarbyl, a substituted hydrocarbyl, an aryl, and a substituted aryl; and
wherein m is an integer of at least 1.
18 . The protected nucleic acid of claim 17 , wherein Q is G, wherein said thiocarbon protecting group is:
said R 4 is cyclopentyl, and said R 5 is 2-cyanoethyl or methyl.