Reagents and methods for esterification

Patent metadata

Field	Value
Publication number	US-10428323-B2
Application number	US-201715730197-A
Country	US
Kind code	B2
Filing date	Oct 11, 2017
Priority date	Apr 9, 2015
Publication date	Oct 1, 2019
Grant date	Oct 1, 2019

Abstract

Methods and reagents for esterification of biological molecules including proteins, polypeptides and peptides. Diazo compounds of formula I:

where R is hydrogen, an alkyl, an alkenyl or an alkynyl, R A represents 1-5 substituents on the indicated phenyl ring and R M is an organic group, which includes a label, a cell penetrating group, a cell targeting group, or a reactive group or latent reactive group for reaction to bond to a label, a cell penetrating group, or a cell targeting group, among other organic groups are useful for esterification of biological molecules. Also provided are diazo compounds which are bifunctional and trifunctional coupling reagents as well as reagents for the synthesis of compounds of formula I.

First claim

We claim:

1. A method for esterifying one or more carboxylic acid groups in an organic or biological molecule which comprises contacting the organic or biological molecule with a compound of formula I:

or salts thereof, where:
R is an alkyl, alkenyl, alkynyl group or hydrogen,
R A is an alkyl or alkoxy at the para position on the indicated phenyl ring, and
R M is an alkyl, alkenyl, alkynyl, cycloalkyl, aryl, or arylalkyl group which is optionally substituted with one or more alkyl, alkoxy, aryl, alkylaryl, halogen, haloalkyl, or haloalkoxy group.

2. A method for enhancing cellular uptake of an organic or biological molecule having one or more carboxylate groups which comprises esterifying the organic or biological molecule by the method of claim 1 .

3. The method of claim 1 , wherein:
R M is an alkyl, alkenyl, alkynyl, phenyl or benzyl group.

4. The method of claim 1 , wherein R A is an alkyl group having 1-6 carbon atoms.

5. The method of claim 1 , wherein R M is an alkyl group having 1-6 carbon atoms or an alkynyl group having 2-6 carbon atoms.

6. The method of claim 1 , wherein R and R M are independently methyl or ethyl groups.

7. The method of claim 1 , wherein: R is alkyl, R A is an alkyl, and R M is an alkyl, alkenyl, alkynyl or aryl group.

8. The method of claim 7 , wherein R M is an alkyl.

9. The method of claim 7 , wherein R, R A and R M are all methyl groups.

10. The method of claim 1 , wherein R M is an alkyl, or a benzyl group.

11. The method of claim 10 , wherein R is hydrogen, or an alkyl group.

12. The method of claim 11 , wherein R A is an alkyl group.

13. The method of claim 11 , wherein R A is methyl group.

14. The method of claim 1 , wherein R A is an alkoxy.

15. The method of claim 14 , wherein R M is an alkyl, or a benzyl group.

16. The method of claim 15 , wherein R is hydrogen, or an alkyl group.

17. The method of claim 1 , wherein R A is an alkoxy group having 1-6 carbon atoms.

18. The method of claim 17 , wherein R M is an alkyl, or a benzyl group.

19. The method of claim 18 , wherein R is hydrogen, or an alkyl group.

20. The method of claim 1 , wherein R A is methoxy.

Assignees

• Wisconsin Alumni Res Found

Inventors

• Raines Ronald T
• Mix Kalie

Classifications

• C07C231/12

  by reactions not involving the formation of carboxamide groups · CPC title

• C07K1/13

  Labelling of peptides · CPC title

• C07D207/46

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

• C12N9/96 Primary

  Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates · CPC title

• C07C269/06

  by reactions not involving the formation of carbamate groups · CPC title