Branched chain-containing aromatic compound

A method of protecting a carboxyl group or an amido group, wherein R is a hydrogen atom, an alkyl group, or an aralkyl group, of amino acid or peptide, comprising reacting said carboxyl group or said amido group with a branched chain-containing aromatic compound represented by formula (I):

• wherein
• each Q is independently a single bond, or —O—, —S—, —C(═O)O—, —C(═O)NH— or —NH—;
• each Ra is independently an organic group having at least one aliphatic hydrocarbon group having one or more branched chains, wherein a total number of branched chains in each Ra is not less than 3 and a total carbon number in each Ra is not less than 14 and not more than 300;
• k is an integer of 1 to 4;
• R1 is a hydrogen atom or, when Z is a group represented by formula (a), it optionally forms a single bond together with R2 to form a fluorene ring together with ring B;
• ring A optionally further has, in addition to R1, (QRa)k, and C(X)(Y)Z or more substituents 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;
• X is a hydrogen atom or a phenyl group;
• Y is a hydroxyl group, an —NHR group (wherein R is a hydrogen atom, an alkyl group, or an aralkyl group), or a halogen atom;
• and
• Z is a hydrogen atom or a group represented by formula (a):
• wherein
• * indicates the bonding position;
• m is an integer of 0 to 4;
• each Q is as defined above
• each Rb is independently an organic group having at least one aliphatic hydrocarbon group having one or more branched chains, wherein a total number of the branched chain in each Rb is not less than 3 and a total carbon number in each Rb is not less than 14 and not more than 300;
• R2 is a hydrogen atom, or optionally forms a single bond together with R1 to form a fluorene ring together with ring A;
• and
• ring B optionally further has, in addition to (QRb)m and R2, one or more substituents 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;
• wherein said organic group having at least one aliphatic hydrocarbon group having one or more branched chains, a total number of the branched chain of not less than 3 and a total carbon number of not less than 14 and not more than 300 for each Ra and Rb is a group having 3 or more of the same or different divalent groups represented by formula (b):
• wherein
• * indicates the bonding position with the adjacent atom;
• R3 and R4 are each independently a hydrogen atom or a C1-4 alkyl group;
• X1 is a single bond, a C1-4 alkylene group, or an oxygen atom,
• provided that R3 and R4 are not hydrogen atoms at the same time.

A branched chain-containing aromatic compound adduct which is protected by the branched chain-containing aromatic compound represented by formula (I):

• wherein
• each Q is independently a single bond, or —O—, —S—, —C(═O)O—, —C(═O)NH— or —NH—;
• each Ra is independently an organic group having at least one aliphatic hydrocarbon group having one or more branched chains, wherein a total number of branched chains in each Ra is not less than 3 and a total carbon number in each Ra is not less than 14 and not more than 300;
• k is an integer of 1 to 4;
• R1 is a hydrogen atom or, when Z is a group represented by formula (a), it optionally forms a single bond together with R2 to form a fluorene ring together with ring B;
• ring A optionally further has, in addition to R1, (QRa)k, and C(X)(Y)Z, one or more substituents 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;
• X is a hydrogen atom or a phenyl group;
• Y is a hydroxyl group, an —NHR group (wherein R is a hydrogen atom, an alkyl group, aralkyl group), or a halogen atom;
• and
• Z is a hydrogen atom or a group represented by formula (a):
• wherein
• * indicates the bonding position;
• m is an integer of 0 to 4;
• each Q is as defined above;
• each Rb is independently an organic group having at least one aliphatic hydrocarbon group having one or more branched chains, wherein a total number of the branched chain in each Rb is not less than 3 and a total carbon number in each Rb is not less than 14 and not more than 300;
• R2 is a hydrogen atom, or optionally forms a single bond together with R1 to form a fluorene ring together with ring A;
• and
• ring B optionally further has, in addition to (ORb)m and R2, one or more substituents 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;
• wherein said organic group having at least one aliphatic hydrocarbon group having one or more branched chains, a total number of the branched chain of not less than 3 and a total carbon number of not less than 14 and not more than 300 for each Ra and Rb is a group having 3 or more of the same or different divalent groups represented by formula (b):
• wherein
• * indicates the bonding position with the adjacent atom;
• R3 and R4 are each independently a hydrogen atom or a C1-4 alkyl group;
• X1 is a single bond, a C1-4 alkylene group, or an oxygen atom,
• provided that R3 and R4 are not hydrogen atoms at the same time.

A method of producing a peptide comprising:

• (1) condensing a branched chain-containing aromatic compound with a C-terminus of a first N-protected amino acid or an N-protected peptide in a solvent solubilizing said compound, to obtain an N-protected C-protected amino acid or a first N-protected C-protected peptide having a C-terminus protected with an anchor which is a protecting group derived from the compound;
• (2) removing the N-terminal protecting group from said N-protected C-protected amino acid or N-protected C-protected peptide to obtain a C-protected amino acid or C-protected peptide;
• (3) condensing a second N-protected amino acid or N-protected peptide with the N-terminus of said C-protected amino acid or C-protected peptide to obtain a second N-protected C-protected peptide;
• and
• (4) removing the N-terminal protecting group and the C-terminal anchor from said second N-protected C-protected peptide, to obtain said peptide,
• wherein said branched chain-containing aromatic compound is represented by formula (I):
• wherein
• each Q is independently a single bond, or —O—, —S—, —C(═O)O—, —C(═O)NH— or —NH—;
• each Ra is independently an organic group having at least one aliphatic hydrocarbon group having one or more branched chains, wherein a total number of branched chains in each Ra is not less than 3 and a total carbon number in each Ra is not less than 14 and not more than 300;
• k is an integer of 1 to 4;
• R1 is a hydrogen atom or, when Z is a group represented by formula (a), it optionally forms a single bond together with R2 to form a fluorene ring together with ring B;
• ring A optionally further has, in addition to R1, (QRa)k, and C(X)(Y)Z, one or more substituents 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;
• X is a hydrogen atom or a phenyl group;
• Y is a hydroxyl group, an —NHR group (wherein R is a hydrogen atom, an alkyl group, or an aralkyl group), or a halogen atom;
• and
• Z is a hydrogen atom or a group represented by formula (a):
• wherein
• * indicates the bonding position;
• m is an integer of 0 to 4;
• each Q is as defined above,
• each Rb is independently an organic group having at least one aliphatic hydrocarbon group having one or more branched chains, wherein a total number of the branched chain in each Rb is not less than 3 and a total carbon number in each Rb is not less than 14 and not more than 300;
• R2 is a hydrogen atom, or optionally forms a single bond together with R1 to form a fluorene ring together with ring A;
• and
• ring B optionally further has, in addition to (QRb)m and R2, one or more substituents 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;
• wherein said organic group having at least one aliphatic hydrocarbon group having one or more branched chains, a total number of the branched chain of not less than 3 and a total carbon number of not less than 14 and not more than 300 for each Ra and Rb is a group having 3 or more of the same or different divalent groups represented by formula (b):
• wherein
• * indicates the bonding position with the adjacent atom;
• R3 and R4 are each independently a hydrogen atom or a C1-4 alkyl group;
• X1 is a single bond, a C1-4 alkylene group, or an oxygen atom,
• provided that R3 and R4 are not hydrogen atoms at the same time.