Method of producing nucleic acid compound, and nucleic acid compound

A method of producing a nucleic acid compound,

• wherein a nucleic acid compound in which a 3-position of a ribose structure is protected by a structure represented by Formula (1) is used,
• in Formula (1), a ring A represents a naphthalene ring,
• YA represents *—OCR2—**, *—NRCR2—**, or *—SCR2—**, where R's each independently represent a hydrogen atom, an alkyl group, an aromatic group, or an aromatic group-substituted alkyl group,
• k represents an integer of 1 to 5,
• a wavy line portion and * represent a bonding position to L in Formula (2), ** represents a bonding position to the ring A,
• RA's are each independently an aliphatic hydrocarbon group or an organic group having an aliphatic hydrocarbon group, where at least one aliphatic hydrocarbon group in k pieces of RA's has 12 or more carbon atoms, and
• the ring A may further have a substituent in addition to YA and RA,
• wherein the nucleic acid compound protected by the structure represented by Formula (1) is a compound represented by Formula (2),
• in Formula (2), m represents any integer of 0 or more,
• n represents 1 to 6,
• Bases each independently represent a nucleic acid base or a modified nucleic acid base,
• P1 represents a hydrogen atom or a hydroxy protective group,
• R1 represents an oxygen atom, a sulfur atom, or a borano group,
• R2 represents a hydrogen atom, a substituted or unsubstituted hydroxy group, a substituted or unsubstituted mercapto group, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted amino group,
• X's each independently represent a hydrogen atom, a hydroxy group, a halogen atom, or an organic group that is crosslinked to a carbon atom at a 4′-position of a ribose structure,
• L's each independently represent a single bond or a divalent linking group,
• the ring A represents a naphthalene ring,
• YA's each independently represent a single bond, *—OCR2—**, *—NRCR2—**, or *—SCR2—**,
• where * represents a bonding position to L,
• ** represents a bonding position to the ring A,
• R's each independently represent a hydrogen atom, an alkyl group, an aromatic group, or an aromatic group-substituted alkyl group,
• adjacent L and YA do not simultaneously represent a single bond,
• k represents an integer of 1 to 5,
• RA's are each independently an aliphatic hydrocarbon group or an organic group having an aliphatic hydrocarbon group, where at least one aliphatic hydrocarbon group in k pieces of RA's has 12 or more carbon atoms, and
• the ring A may further have a substituent in addition to YA and RA,
• wherein P1 represents a hydrogen atom, and
• a liquid phase synthesis method is used, where the method includes in the following order;
• a step B:
• a step of reacting the nucleic acid compound in which the structure represented by Formula (1) is bonded to a terminal at a 3-position of a ribose structure, and a nucleic acid compound in which a 3-position of a ribose structure is subjected to phosphoramidation and a hydroxy group at a 5-position of the ribose structure is protected by a protective group capable of being deprotected by a weak acid, to be condensed by a phosphite triester bond,
• a step C:
• a step of reacting the nucleic acid compound obtained in the step B with an oxidizing agent or a sulfurizing agent to convert the phosphite triester bond of the nucleic acid compound into a phosphate triester bond or a thiophosphate triester bond,
• a step A:
• a step of deprotecting a terminal protective group at a 5-position of the nucleic acid compound obtained in the step C, and
• a step D:
• a step of precipitating the nucleic acid compound obtained in the step A.

A nucleic acid compound, wherein a hydroxy group of a 3-position of a ribose structure is protected by a structure represented by Formula (1a),

• in Formula (1a), a ring A represents a naphthalene ring,
• YA represents *—OCR2—**, *—NRCR2—**, or *—SCR2—**,
• R's each independently represent a hydrogen atom, an alkyl group, an aromatic group, or an aromatic group-substituted alkyl group,
• k represents an integer of 1 to 5,
• a wavy line portion and * represent a bonding position to a hydroxy group at a 3-position of a ribose structure,
• ** represents a bonding position to a ring A,
• RA's are each independently an aliphatic hydrocarbon group or an organic group having an aliphatic hydrocarbon group, where at least one aliphatic hydrocarbon group in k pieces of RA's has 12 or more carbon atoms, and
• the ring A may further have a substituent in addition to YA and RA.