Branched monodispersed polyethylene glycol, intermediate and methods for producing same

Patent metadata

Field	Value
Publication number	US-11905367-B2
Application number	US-201916981395-A
Country	US
Kind code	B2
Filing date	Mar 19, 2019
Priority date	Mar 20, 2018
Publication date	Feb 20, 2024
Grant date	Feb 20, 2024

Abstract

A branched monodispersed polyethylene glycol represented by the formula (1):wherein X1 is a functional group that forms a covalent bond upon a reaction with a functional group present in a biofunctional molecule; n is an integer of 4 to 50, which represents number of repeating units of ethylene oxide units; and L1 represents a single bond, —NH—, -L2-(CH2)m1- or -L2-(CH2)m1-L3-(CH2)m2-, L2 represents an ether bond, an amide bond, an urethane bond or a single bond, L3 represents an ether bond, an amide bond or an urethane bond, and m1 and m2 represent each independently an integer of 1 to 5.

First claim

The invention claimed is:

1. A branched monodispersed polyethylene glycol represented by formula (1) wherein 90% or more of PEG compounds constituting the branched monodispersed PEG have the same number of repeating ethylene oxide units n:

wherein, in the formula (1),
X 1 is a functional group that forms a covalent bond upon a reaction with a functional group present in a biofunctional molecule and is selected from the group consisting of an active ester group, an active carbonate group, an aldehyde group, an isocyanate group, an isothiocyanate group, an epoxy group, a maleimide group, a vinyl sulfone group, an acryl group, a sulfonyloxy group, a carboxy group, a thiol group, a dithiopyridyl group, an α-haloacetyl group, an alkynyl group, an allyl group, a vinyl group, an amino group, an oxyamino group, a hydrazide group and an azide group;
n is an integer of 8 to 24, which represents number of repeating units of ethylene oxide units; and
L 1 represents a single bond, —NH—, -L 2 -(CH 2 ) m1 - or -L 2 -(CH 2 ) m1 -L 3 -(CH 2 ) m2 -, L 2 represents an ether bond, an amide bond, an urethane bond or a single bond, L 3 represents an ether bond, an amide bond or an urethane bond, and m1 and m2 represent each independently an integer of 1 to 5.

2. An intermediate of a branched monodispersed polyethylene glycol, which is represented by formula (2):

wherein, in the formula (2),
Y 1 is an amino group; and
n is an integer of 8 to 24, which represents number of repeating units of ethylene oxide units.

3. A method for producing the intermediate according to claim 2 , wherein the following three steps:
a step (A) of coupling a monodispersed polyethylene glycol derivative represented by following formula (3) and a compound represented by following formula (4) to obtain a compound represented by following formula (5):
A-(CH 2 CH 2 O) n -CH 3   (3)

wherein, in the formula (3),
A is a leaving group; and
n is an integer of 8 to 24, which represents number of repeating units of ethylene oxide units,

wherein, in the formula (4),
Y 2 is a nitrogen atom; and
k is an integer of 2,

wherein, in the formula (5),
Y 2 is a nitrogen atom;
n is an integer of 8 to 24, which represents number of repeating units of ethylene oxide units,
k is an integer of 2,
a step (B) of subjecting the compound represented by the formula (5) to extraction purification with water and an organic solvent, and
a step (C) of performing a treatment of cleaving the benzyl group contained in the compound represented by the formula (5) to obtain the intermediate of the branched monodispersed polyethylene glycol represented by the formula (2), are performed in the order of the step (A), the step (B) and the step (C).

4. The method according to claim 3 , wherein the step (C) is effected by performing a catalytic hydrogen reduction treatment.

5. A method for producing the branched monodispersed polyethylene glycol according to claim 1 , comprising a step (D) of converting Y 1 of an intermediate of a branched monodispersed polyethylene glycol, which is represented by formula (2) into L 1 -X 1 :

wherein, in the formula (2),
Y 1 is an amino group; and
n is an integer of 8 to 24, which represents number of repeating units of ethylene oxide.

Assignees

• Nof Corp

Inventors

• HAMURA Mika
• Matsuno Yuki
• Yoshioka Hiroki

Classifications

• C08G65/3311 Primary

  containing a hydroxy group · CPC title

• C08G65/3332

  containing carboxamide group · CPC title

• C07C205/43 Primary

  to carbon atoms of the same non-condensed six-membered aromatic ring or to carbon atoms of six-membered aromatic rings being part of the same condensed ring system · CPC title

• C07D207/46 Primary

  with hetero atoms directly attached to the ring nitrogen atom · CPC title

• C07C43/164

  containing six-membered aromatic rings · CPC title