Reagents and methods for esterification

1. 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 R 1 and R 2 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:

R 1 comprises an electron withdrawing group selected from nitro, cyano, halogen, ammonium (—NR′ 3 + ), aryloxy, alkoxy, sulfonic ester (—SO 2 —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

R 2 is selected from the group consisting of an alkyl, aryl, alkyl aryl, heteroaryl, and heterocyclic group, each of which is optionally substituted.

2. The method of claim 1 , wherein:

optional substitution is substitution with one or more oxo group, thioxo group, halogen, nitro, cyano, cyanate, azido, thiocyano, isocyano, isothiocyano, sulfhydryl, hydroxyl, alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, alkynyloxy, aryl, aryloxy, heteroaryl, heteroaryloxy, carbocyclyl, carbocyclyloxy, heterocyclyl, heterocyclyloxy, alkylthio, alkenylthio, alkynylthio, arylthio, thioheteroaryl, thiocarbocyclyl, thioheterocyclyl, —COR s , —COH, —OCOR s , —OCOH, —CO—OR s , —CO—OH, —CO—O—CO—R s , —CON(R s ) 2 , —CONHR s , —CONH 2 , —NR s —COR s , —NHCOR s , —NHR s , —N(R s ) 2 , —O—SO 2 —R s , —SO 2 —R s , —SO 2 —NHR s , —SO 2 —N(R s ) 2 , —NR s —SO 2 —R s , —NH—SO 2 —R s , —NR s CO—N(R s ) 2 , —NH—CO—N HRs, —O—PO(OR s ) 2 , —O—PO(OR s )(N(R s ) 2 ), —O—PO(N(R s ) 2 ) 2 , —N—PO(OR s ) 2 , —N—PO(OR s )(N(R s ), —P(R s ) 2 , —B(OH) 2 , —B(OH)(OR s ), or —B(OR s ) 2 , where each R s independently is an alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, or heterocyclyl group or two R s within the same substituent optionally together form a carbocyclic or heterocyclic ring having 3 to 10 ring atoms.

3. The method of claim 1 , wherein R 1 is —CON(R′) 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.

4. The method of claim 1 , wherein R 1 is —CON(R′) 2 , where each R′ independently, is hydrogen, or an optionally substituted alky, alkenyl, alkynyl, aryl, alkylaryl, or arylalkyl.

5. The method of claim 4 , wherein optional substitution is substitution with one or more oxo group, thioxo group, halogen, nitro, cyano, azido, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocyclyl, alkylthio, alkenylthio, alkynylthio, arylthio, thioheteroaryl, thiocarbocyclyl, thioheterocyclyl, —COR s , —COH, —OCOR s , —OCOH, —CO—OR s , —CO—OH, —CO—O—CO—R s , where each R s independently is an alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, or heterocyclyl group.

6. The method of claim 4 , wherein optional substitution is substitution with one or more alkyl, aryl, heteroaryl, carbocyclyl, heterocyclyl or alkylthio.

7. The method of claim 4 , wherein R 2 is an alkyl, alkenyl, alkynyl, aryl, alkylaryl, arylalkyl, heteroaryl, or heterocyclic group, each of which groups is optionally substituted.

8. The method of claim 4 , wherein R 2 is an aryl, alkylaryl, heteroaryl, or heterocyclic group, each of which groups is optionally substituted.

9. The method of claim 1 , wherein R 2 is an optionally substituted aryl group.

10. The method of claim 4 , wherein R 2 is an optionally substituted aryl group.

11. The method of claim 4 , wherein R 2 is an optionally substituted phenyl group.

12. The method of claim 11 , wherein R 2 is a phenyl ring substituted with an optionally substituted methyl or methoxy group.

13. The method of claim 12 , wherein optional substitution is substitution with one or more —COR s , —OCOR s , —CO—OR s , or —CO—O—CO—R s , where each R s independently is an alkyl, alkenyl, alkynyl, aryl, or carbocyclyl group.

14. The method of claim 12 , wherein optional substitution is substitution with one or more —OCOR s , where each R s independently is an alkyl, alkenyl, alkynyl, aryl, or carbocyclyl group.

15. The method of claim 11 , wherein optional substitution is substitution with one or more nitro, cyano, azido, alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, heterocyclyl, —COR s , —COH, —OCOR s , —OCOH, —CO—OR s , —CO—OH, or —CO—O—CO—R s , where each R s independently is an alkyl, alkenyl, alkynyl, aryl, heteroaryl, carbocyclyl, or heterocyclyl group.

16. The method of claim 11 , wherein optional substitution is substitution with one or more —COR s , —OCOR s , —CO—OR s , or —CO—O—CO—R s .

17. The method of claim 1 , wherein the reaction is carried out in buffered aqueous solvent at a pH between 5.5 and 6.5.

18. The method of claim 1 , wherein the reaction is carried out in aqueous acetonitrile.

19. The method of claim 1 , wherein the compound to be esterified contains one or more amine groups, alcohol groups or thiol groups in addition to the one or more carboxylic acid groups.

20. The method of claim 1 , where the compound containing one or more carboxylic acid groups is a peptide or protein.