Modified oligonucleotides and methods for their synthesis

A compound of Formula (I)

• wherein
• Z is selected from —O−, —S−, —Se−, —(N−)RN, or a protecting group (PG);
• X is selected from the 5′-O— of a nucleoside or oligonucleotide and Y is selected from the 3′-O— of a nucleoside oligonucleotide;
• —H, —OH, —SH, —NHRN, —O-PG, or —S-PG, wherein PG is a protecting group;
• a linker, a monophosphate or diphosphate, or a label or quencher;
• or
• Y is selected from the 3′-O— of a nucleoside or oligonucleotide and X is selected from the 5′-O— of a nucleoside, oligonucleotide, —H, —OH, —SH, —NHRN, —O-PG, or —S-PG, wherein PG is a protecting group;
• a linker, a monophosphate or diphosphate, or a label or quencher;
• R1 is selected from —NR1AR1B, —OR3, —SR3, —H, —S(O)H, —S(O)R3, —S(O)2H, —S(O)2R3, —S(O)2NH2, —S(O)2NHR3, —S(O)2NR32, —C1-10alkyl, —C2-10alkenyl, —C2-10alkynyl, or —C6-10 aryl;
• R2 is selected from —H, —NR2AR2B, —OR3, —SR3, —CN, —S(O)H, —S(O)R3, —S(O)2H, —S(O)2R3, —S(O)2NH2, —S(O)2NHR3, —S(O)2NR32, —C1-10alkyl, —C2-10alkenyl, —C2-10alkynyl, or —C6-10aryl;
• wherein each R1A, R1B, R2A, and R2B is independently selected from —H, —C1-10alkyl, —C2-10alkenyl, —C2-10alkynyl, or —C6-10aryl;
• optionally, wherein R1A and R2A together form an alkylene chain of 2-4 atoms in length;
• optionally, wherein R1A and R1B, together with the atom to which they are bound, form a 5-8 membered heterocyclic substituent moiety, selected from the group consisting of N-pyrrolidinyl, N-piperidinyl, N-azepanyl, or N-azocanyl;
• optionally, wherein R2A and R2B, together with the atom to which they are bound, form a 5-8 membered heterocyclic substituent moiety, selected from the group consisting of N-pyrrolidinyl, N-piperidinyl, N-azepanyl, or N-azocanyl;
• R3 is selected from —C1-10alkyl, —C2-10alkenyl, —C2-10alkynyl, or —C6-10aryl;
• wherein the linker is selected from the group consisting of succinyl, diglycolyl, oxalyl, hydroquinone-O,O′-diacetyl (Q-linker), phthaloyl, 4,5-dichlorophthaloyl, malonyl, glutaryl, diisopropylsilyl and 1,1,3,3-tetraisopropyldisiloxane-1,3-diyl, or dodecane-12-oxy-1-phosphatidyl,
• the label is fluorescein-derived substituent,
• the quencher is 2-((2-hydroxy-ethyl)-{4-[2-methoxy-5-methyl-4-(4-methyl-2-nitro-phenylazo)-phenylazo]-phenyl}-amino)-ethanol-derived substituent;
• wherein RN is —H or —C1-4alkyl;
• and
• when Z is PG, the compound is a salt with anion counterpart selected from the group consisting of I−, Br−, Cl−, N-succinimido ((CH2)2(CO)2N−), CCl3−, CBr3−, CI3−, CHI2−, trifluoromethanesulfonate (CF3SO3−), p-toluenesulphonate (C7H7SO3−), dichlorophosphate (PO2Cl2−), perchlorate (ClO4−), tetrafluoroborate (BF4−), tetraphenylborate (BPh4−), or hexafluorophosphate (PF6−).