Morpholino oligonucleotide manufacturing method

A morpholino nucleotide represented by formula (I):

• wherein
• m is any integer of not less than 0;
• each of m+1 Base is independently an optionally protected nucleic acid base;
• P1 is a hydrogen atom, or a temporary protecting group removable under acidic conditions;
• each of m X is independently a C1-6 alkoxy group, a di-C1-6 alkylamino group, or a piperazino group wherein a nitrogen atom at the 4-position is protected by a protecting group and further optionally substituted;
• each of m W is independently an oxygen atom or a sulfur atom;
• S1 is a single bond, or a group represented by *O—S2**, wherein * indicates the bonding position to L, ** indicates the bonding position to a 5′-hydroxy group, and S2 is a spacer having a main chain containing 1 to 20 atoms;
• L is a single bond, or a group represented by the formula (a1):
• wherein
• * indicates the bonding position to Y;
• ** indicates the bonding position to S1;
• L1 is an optionally substituted divalent C1-22 hydrocarbon group;
• and
• L2 is C(═O) or a group represented by ***N(R3)—R1—N(R2)C(═O)**, wherein ** indicates the bonding position to L1, *** indicates the bonding position to Y, R1 is an optionally substituted C1-22 alkylene group, R2 and R3 are each independently a hydrogen atom or an optionally substituted C1-22 alkyl group, or R2 and R3 are optionally joined to form an optionally substituted C1-22 alkylene bond;
• Y is a single bond, an oxygen atom or NR, wherein R is a hydrogen atom, an alkyl group or an aralkyl group;
• and
• Z is a group represented by formula (a2):
• wherein
• * indicates the bonding position to Y;
• R4 is a hydrogen atom, or when Rb is a group represented by the following formula (a3), R4 is optionally a single bond or —O— in combination with R6 to form a fluorenyl group or a xanthenyl group together with ring B;
• each of k Q is independently a single bond, or —O—, —S—, —OC(═O)—, —NHC(═O)— or —NH—;
• each of k R5 is independently an organic group containing an alkyl group having not less than 10 and not more than 300 carbon atoms and/or an alkenyl group containing not less than 10 and not more than 300 carbon atoms;
• k is an integer of 1 to 4;
• ring A optionally further has, in addition to k of QR5, a substituent selected from the group consisting of a halogen atom, a C1-6 alkyl group optionally substituted by one or more halogen atoms, and a C1-6 alkoxy group optionally substituted by one or more halogen atoms;
• Ra is a hydrogen atom;
• Rb is a hydrogen atom, or a group represented by formula (a3):
• wherein
• * indicates a bonding position;
• j is an integer of 0 to 4;
• each of j Q is as defined above;
• each of j R7 is independently an organic group having an alkyl group containing not less than 10 and not more than 300 carbon atoms and/or an alkenyl group containing not less than 10 and not more than 300 carbon atoms;
• R6 is a hydrogen atom, or optionally a single bond or —O— in combination with R4 to form a fluorenyl group or a xanthenyl group together with ring A;
• and
• ring B optionally further has, in addition to j of QR7, a substituent selected from the group consisting of a halogen atom, a C1-6 alkyl group optionally substituted by one or more halogen atoms, and a C1-6 alkoxy group optionally substituted by one or more halogen atoms, or
• Ra and Rb are joined to form an oxygen atom.