Thiocarbon-protecting groups for RNA synthesis

A method comprising:

• (a) providing a nucleoside residue, wherein said nucleoside residue comprises an unprotected hydroxyl group and a 2′-protected nucleotide monomer, wherein said 2′-protected nucleotide monomer has the structure of formula (I):
• wherein:
• BP is a protected or unprotected heterocyclic group having a 3 to 20 membered ring system;
• one of R1 and R2 is a protecting group, and the other of R1 and R2 is a phosphoramidite group;
• R3 is a hydrocarbyl that is not a silyl-containing hydrocarbyl or a substituted hydrocarbyl that is not a silyl-containing hydrocarbyl, and wherein R3 is described by the structure:
• wherein R3′, R3″ and R3′″ are each independently selected from H, a hydrocarbyl, a substituted hydrocarbyl, an aryl and a substituted aryl, wherein at least one of R3′, R3″ and R3′″ is H;
• X and Y are each independently sulfur or oxygen, wherein at least one of X and Y is sulfur;
• and
• (b) contacting said nucleoside residue with said 2′-protected nucleotide monomer under conditions sufficient to covalently bond said phosphoramidite group of said 2′-protected nucleotide monomer to said unprotected hydroxyl group of said nucleoside residue and produce an internucleotide bond.

A method, comprising:

• (a) providing a nucleoside residue, wherein said nucleoside residue comprises an unprotected hydroxyl group and a 2′-protected nucleotide monomer, wherein said nucleoside residue is covalently bound to a solid support and said 2′-protected nucleotide monomer has the structure of formula (I):
• wherein:
• BP is a protected or unprotected heterocyclic group having a 3 to 20 membered ring system;
• one of R1 and R2 is a protecting group, and the other of R1 and R2 is a phosphoramidite group;
• R3 is a hydrocarbyl that is not a silyl-containing hydrocarbyl or a substituted hydrocarbyl that is not a silyl-containing hydrocarbyl, and wherein R3 is described by the structure:
• wherein R3′, R3″ and R3′″ are each independently selected from H, a hydrocarbyl, a substituted hydrocarbyl, an aryl and a substituted aryl, wherein at least one of R3′, R3″ and R3′″ is H;
• X and Y are each independently sulfur or oxygen, wherein at least one of X and Y is sulfur;
• and
• (b) contacting said nucleoside residue with said 2′-protected nucleotide monomer under conditions sufficient to covalently bond said phosphoramidite group of said 2′-protected nucleotide monomer to said unprotected hydroxyl group of said nucleoside residue and produce an internucleotide bond;
• (c) oxidizing said internucleotide bond to produce a nucleic acid;
• (d) cleaving said nucleic acid from said solid support to produce a free nucleic acid;
• and
• (e) chemically modifying said free nucleic acid to produce a modified nucleic acid.

A 2′-O-protected nucleic acid comprising the structure:

• wherein:
• BP is a protected or unprotected heterocyclic group having a 3 to 20 membered ring system;
• Q is a thiocarbon protecting group having one of the following structures:
• —C(═Y)—X—R3,
• wherein X and Y are each independently sulfur or oxygen, wherein at least one of X and Y is sulfur;
• R3 is a hydrocarbyl or a substituted hydrocarbyl that is not a silyl-containing hydrocarbyl, and wherein R3 is described by the structure:
• wherein R3′, R3″ and R3′″ are each independently selected from H, a hydrocarbyl, substituted hydrocarbyl, an aryl and a substituted aryl, wherein at least one of R3′, R3″ and R3′″ is H;
• R12 is selected from the group consisting of hydrogen, a hydrocarbyl, a substituted hydrocarbyl, an aryl and a substituted aryl;
• and
• m is an integer of at least 2.