# US 8,785,660 B2 · Polyoxyalkylene-modified lipid and method for producing the same

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 8,785,660 B2
- Document ID: US8785660B2
- Status: Granted
- Kind: B2
- Application number: 13/431,590
- Filed: 2012-03-27
- Published: 2012-10-04
- Granted: 2014-07-22
- Earliest claimed: 2011-03-29
- Assignees: Nof Corporation
- Applicants: Satoshi Matsuo; Yuji Yamamoto; Chika Itoh
- Inventors: Satoshi Matsuo; Yuji Yamamoto; Chika Itoh
- Web page: https://patentgrep.com/patent/US8785660B2

## CPC

- C07D 207/456: with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to other ring carbon atoms
- C07C 269/04: from amines with formation of carbamate groups
- C07C 271/16: to carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen atoms
- C07D 207/452: with hydrocarbon radicals, substituted by hetero atoms, directly attached to the ring nitrogen atom
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS

## Abstract

Provided are a thiol-reactive polyoxyalkylene-modified lipid which can be used to chemically modify bioactive substances and which can be used for drug delivery systems such as liposomes and a method for producing the same. The polyoxyalkylene-modified lipid is represented by the following formula (1): (wherein, R1 and R2 are hydrocarbon groups which are the same as or different from each other and which contain 4 to 24 carbon atoms, R3 is a divalent hydrocarbon group containing 1 to 6 carbon atoms, OA is oxyalkylene groups containing 2 to 4 carbon atoms, n is the average addition mole number of the oxyalkylene groups and is 5 to 1,000, and Z is a group containing either maleimide or iodoacetamide.)

## Claims

### Claim 1

A method for producing a polyoxyalkylene-modified lipid represented by the following formula (1), comprising Step (II) after Step (I):
wherein, R1 and R2 are hydrocarbon groups which are the same as or different from each other and which contain 4 to 24 carbon atoms, R3 is a divalent hydrocarbon group containing 1 to 6 carbon atoms, OA is oxyalkylene groups containing 2 to 4 carbon atoms, n is the average addition mole number of the oxyalkylene groups and is 5 to 1,000, and Z is a group containing either maleimide or iodoacetamide;
Step (I): a step of obtaining a compound represented by the following formula (3) by deprotecting P of a compound represented by the following formula (2) with a methanesulfonic acid:
P—R3—(OA)n-Z (2)
wherein, OA is oxyalkylene groups containing 2 to 4 carbon atoms, n is the average addition mole number of the oxyalkylene groups and is 5 to 1,000, R3 is a divalent hydrocarbon group containing 1 to 6 carbon atoms, Z is a group containing either maleimide or iodoacetamide, and P is a chemically protected amino group which is to be deprotected with acid;
X—R3—(OA)n-Z (3)
wherein, OA is oxyalkylene groups containing 2 to 4 carbon atoms, n is the average addition mole number of the oxyalkylene groups and is 5 to 1,000, R3 is a divalent hydrocarbon group containing 1 to 6 carbon atoms, Z is a group containing either maleimide or iodoacetamide, and X is an ion pair of an amino group and the methanesulfonic acid;
Step (II): a step of obtaining the compound represented by Formula (1) in such a manner that a solution containing the compound represented by Formula (3) is added dropwise to a solution containing a compound represented by the following formula (4) to cause reaction:
wherein, R1 and R2 are hydrocarbon groups which are the same as or different from each other and which contain 4 to 24 carbon atoms and Y is an activated carbonate group.

### Claim 2 (depends on 1)

The polyoxyalkylene-modified lipid-producing method according to claim 1, wherein Z is a group containing maleimide.

### Claim 3 (depends on 1)

The polyoxyalkylene-modified lipid-producing method according to claim 1, wherein the chemically protected amino group P which is to be deprotected with acid is a t-butyl carbamate group.