Reagents and methods for esterification
AssigneeWisconsin Alumni Research Foundation
InventorsRonald T. Raines, Nicholas McGrath
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Abstract
A method for esterification of one or more carboxylic acid groups in a compound containing one or more carboxylic acid groups wherein the esterification reagent is a diazo-compound of formula: wherein the R1 and R2 groups of the diazo compound are selected such that the corresponding organic compound of formula: exhibits a —C—H pKa value between 18 and 29 as measured in DMSO. Specific reagents and methods for esterification are provided. The esterification reagents provided exhibit high selectivity for esterification of carboxylic acid groups over reaction with amine, alcohol or thiol groups in the compound containing one or more carboxylic acid groups. The method can be used to selectively esterify carboxylic acid groups in peptides or proteins.
Claims20
A method for esterification of one or more carboxylic acid groups in a compound containing one or more carboxylic acid groups which comprises the step of reacting the one or more compounds with a diazo-compound of formula:
- wherein the R1 and R2 groups of the diazo compound are selected such that the corresponding organic compound of formula:
- exhibits a —C—H pKa value between 18 and 29 as measured in DMSO;
- wherein the one or more esters formed are bio-reversible;
- wherein the reaction is carried out in buffered aqueous solvent at a pH between 5 and 7, in the absence of catalyst;
- wherein the compound containing the one or more carboxylic acid groups is not an amino acid;
- and
- wherein:
- R1 comprises an electron withdrawing group selected from nitro, cyano, halogen, ammonium (—NR′3+), aryloxy, alkoxy, sulfonic ester (—SO2—R′), sulfonium (—S(R′)2+), phosphonium (—P(R′)3+), —COOR′, —COR′, —CON(R′)2, —OCOR′, alkylthio, arylthio, aryl, —C≡CR′, and —C═CR′2, where each R′ independently, is hydrogen, or an optionally substituted alky, alkenyl, alkynyl, aryl, alkylaryl, or arylalkyl, where two R′ on the same atom may together with that atom form a 5- to 8-member carbocyclic or heterocyclic ring in which one or more ring atoms can be replaced with —CO—, —O—, —CS—, —S— or —NR—, where R is hydrogen or an alkyl group having 1-3 carbon atoms;
- and
- R2 is selected from the group consisting of an alkyl, aryl, alkyl aryl, heteroaryl, and heterocyclic group, each of which is optionally substituted.
Dependencies are inferred from the claim text.