A method for producing an optically active segment for use in synthesis of a stereocontrolled oligonucleotide, represented by the following formula (I):
- wherein B is independently a nucleoside base unprotected or protected with a protecting group;
- R1 is a substituted or unsubstituted aliphatic group, a substituted or unsubstituted aromatic group, or a substituted or unsubstituted heteroaryl group;
- R2 and R3 are independently a protecting group removable under acidic conditions, a silyl protecting group, or —P(R11) {N(R12)2};
- R3 is —P(R11) {N(R12)2} in the case where R2 is a protecting group removable under acidic conditions or a silyl protecting group, or R3 is a protecting group removable under acidic conditions or a silyl protecting group in the case where R2 is —P(R11) {N(R12)2};
- R4 and R5 are independently H, an alkyl, an alkenyl, a substituted or unsubstituted aromatic group, a substituted or unsubstituted heteroaryl group, a —CH2-substituted or unsubstituted aryl, or a —CH2-substituted silyl;
- R6, R7, R8 and R9 are independently H, a substituted or unsubstituted aliphatic group, or a substituted or unsubstituted aromatic group;
- R11 is independently OCH2CH2CN, SCH2CH2CN, OCH2CH═CH2, or OCH3;
- R12 is a substituted or unsubstituted aliphatic group, or a substituted or unsubstituted aromatic group;
- X is independently H, an alkyl, an O-alkyl, an N-alkyl, or a halogen;
- Y is independently H, NHR13, a halogen, CN, CF3 or a hydroxyl group protected with an acyl protecting group, an ether protecting group or a silyl protecting group, or forms an X-—Y bond with X;
- R13 is independently H, an alkyl, a carbamate, an amide group, or a substituted silyl;
- Z is independently O or S;
- and
- n is an integer 2≤n≤4, and
- wherein in the case where B in formula (I) is a nucleoside protected with a protecting group, the protecting group is an acyl protecting group,
- the method comprising:
- (a) reacting a nucleoside represented by the following formula (II):
- wherein R2 is a protecting group removable under acidic conditions or a silyl protecting group,
- with a compound represented by the following formula (III):
- to prepare a compound having a structure represented by the following formula (IV):
- (b) reacting the compound having a structure represented by formula (IV) with a compound having the structure of formula (V):
- wherein R10 is a phenoxyacetyl or alkyloxycarbonyl protecting group, and subsequently performing a sulfurization reaction to prepare a compound having a structure represented by the following formula (VI):
- (c) reacting a compound obtained through a deprotection reaction of 5′-hydroxyl group of the compound having the structure of formula (VI) with a compound having the structure of formula (IV) and then performing a sulfurization reaction 1 to 4 times, in the case of n=1 to 4 in formula (I);
- and
- (d) performing a deprotection reaction of the protecting group OR10 for 3′-hydroxyl group of the compound obtained in (b) or (c), and then reacting the product with a phosphitylating compound having a structure of R11P{N(R12)2}2 to prepare a segment having the structure of formula (I).