Production method of polyoxyethylene derivative having plurality of hydroxyl groups at terminal

Patent metadata

Field	Value
Publication number	US-10947343-B2
Application number	US-201816492883-A
Country	US
Kind code	B2
Filing date	Mar 22, 2018
Priority date	Mar 31, 2017
Publication date	Mar 16, 2021
Grant date	Mar 16, 2021

Abstract

A method of producing a polyoxyethylene derivative (1):

where L1 is a divalent linker, X is a functional group capable of reacting with a physiologically active substance, a is 1 or 2, and n is from 11 to 3,650. The method includes Step (A): protecting 4 or 6 hydroxyl groups in a polyhydric alcohol having 5 or 7 hydroxyl groups by cyclic benzylidene acetalization to obtain a compound having a hydroxyl group at a 1-position and a protective group of a cyclic benzylidene acetal structure; Step (B): polymerizing from 11 to 3,650 moles of ethylene oxide to the compound obtained in the step (A) to obtain a polyoxyethylene derivative; Step (C): converting the hydroxyl group at a terminal of the polyoxyethylene derivative to a functional group capable of reacting with a physiologically active substance; and Step (D): deprotecting the protective group of the polyoxyethylene derivative.

First claim

The invention claimed is:

1. A production method of a polyoxyethylene derivative represented by the following formula (1) which comprises performing the following step (A), step (B), step (C) and step (D):

(in the formula (1), L 1 is a divalent linker, X is a functional group capable of reacting with a physiologically active substance, a is 1 or 2, and n is from 11 to 3,650);
Step (A): a step wherein in a polyhydric alcohol having 5 or 7 hydroxyl groups, 4 or 6 hydroxyl groups are protected by cyclic benzylidene acetalization to obtain a compound having the hydroxyl group at a 1-position and a protective group of a cyclic benzylidene acetal structure;
Step (B): a step wherein from 11 to 3,650 moles of ethylene oxide are polymerized to the compound obtained in the step (A) to obtain a polyoxyethylene derivative;
Step (C): a step wherein the hydroxyl group at a terminal of the polyoxyethylene derivative obtained in the step (B) is converted to the functional group capable of reacting with a physiologically active substance; and
Step (D): a step wherein the protective group of the polyoxyethylene derivative is deprotected.

2. The method as claimed in claim 1 , wherein an acidic solution is used as a solvent in the step (A).

3. The method as claimed in claim 1 , wherein the step (C) and the step (D) are performed in succession.

4. The method as claimed in claim 1 , wherein the step (D) is performed under acidic conditions.

5. The method as claimed in claim 1 , wherein the step (D) is performed by a reduction reaction.

6. The method as claimed in claim 2 , wherein the step (C) and the step (D) are performed in succession.

Assignees

• Nof Corp

Inventors

• Yoshioka Hiroki
• Yamamoto Yuji

Classifications

• C08G65/3312

  acyclic · CPC title

• C08G65/2609 Primary

  containing aliphatic hydroxyl groups · CPC title

• C08G65/2606 Primary

  containing hydroxyl groups · CPC title

• C08G65/32

  Polymers modified by chemical after-treatment · CPC title

• A61K47/60

  the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol · CPC title