Coupling agents for peptide synthesis

1. A compound or a salt consisting of an anion and, wherein the compound or the cation of the salt is of the formula

wherein

R 1 and R 2 taken together with the carbon atoms to which they are attached form a pyridyl ring, said pyridyl ring may be unsubstituted or substituted with a lower alkyl group or an electron donating group;

Y 1 is N;

Q 1 is CR 16 ;

R 16 is H or lower alkyl;

R 14 is a positively charged electron withdrawing group,

SO 2 R 17 , lower alkyl carbonyl, lower arylalkyl carbonyl, aryl carbonyl, lower alkyl aryl, or BLK 1 -AA 1

R 17 is aryl, aryl lower alkyl or lower alkyl;

AA 1 is an amino acid or peptide less a hydrogen atom on the N-terminus and an OH on the C-terminus;

BLK 1 is an amino protecting group,

R 10 is OR 12 , lower alkyl, aryl, aryl lower alkyl, lower cycloalkyl, lower cycloalkyl lower alkyl, heterocyclic, heterocyclic lower alkyl, lower cycloalkenyl, or lower cycloalkenyl lower alkyl;

R 11 is OR 13 , lower alkyl, aryl, aryl lower alkyl, lower cycloalkyl, lower cycloalkyl lower alkyl, heterocyclic, heterocyclic lower alkyl, lower cycloalkenyl or lower cycloalkenyl lower alkyl;

and R 10 and R 11 may optionally be connected by a bridging group selected from the group consisting of O, S, NR 30 , or (CHR 30 ) m , wherein each R 30 is independently lower alkyl or hydrogen and m is 1-3; and

R 12 and R 13 are independently lower alkyl, lower cycloalkyl, lower cycloalkyl lower alkyl, heterocyclic, heterocyclic lower alkyl, lower cycloalkenyl or lower cyclalkenyl lower alkyl;

ring A 1 and ring B are independently an aromatic ring containing 6 to 14 ring carbon atoms or cycloalkenyl or cycloalkyl, each containing 5 to 14 ring carbon atoms, and

R b1 , R c1 , R b2 , R c2 are independently hydrogen, lower alkyl or electron donating group;

T is CHR 31 , O, S or NR 30 ; and

R 31 is hydrogen or lower alkyl.

2. The salt according to claim 1 wherein R 14 is a positively charged electron withdrawing group.

3. The salt according to claim 2 wherein R 14 is an electron withdrawing group of the formula

wherein

R 18 , R 19 , R 20 , R 21 , R 22 , R 23 , R 24 and R 25 are independently hydrogen, lower alkyl, or lower alkoxy lower alkyl or R 18 and R 19 taken together with the atoms to which they are attached form a ring containing up to 6 ring atoms and up to a total of 5 carbon ring atoms or R 20 and R 21 taken together with the nitrogen atom to which they are attached form a 5 or 6 membered nitrogen containing heterocyclic ring containing up to a total of 5 carbon ring atoms or R 18 and R 20 taken together with the nitrogen atom and the carbon atom to which they are attached form a heterocyclic ring, or R 22 and R 23 taken together with the atoms to which they are attached form a ring containing up to 6 ring atoms and up to a total of 5 carbon atoms or R 24 and R 25 taken together with the carbon atoms to which they are attached form a ring containing up to 6 ring atoms and up to a total of 5 carbon atoms.

4. The salt according to claim 3 wherein R 14 is

wherein R 19 , R 21 , R 24 and R 25 are independently hydrogen, or lower alkyl or lower alkoxy lower alkyl; and n 1 is 0 or 1.

5. The salt according to claim 4 wherein R 19 and R 21 or R 24 and R 25 are the same.

6. The salt according to claim 1 wherein R 14 is

wherein R 18 , R 19 , R 20 , R 21 , R 22 , R 23 , R 24 and R 25 are independently hydrogen, methyl, ethyl, propyl, butyl, pentyl, or CH 2 CH 2 OCH 2 CH 3 .

7. The salt according to claim 6 wherein R 23 , R 22 , R 20 , R 21 , R 24 , and R 25 are the same or R 18 , R 19 and R 20 are the same or R 19 and R 21 are the same.

8. The compound or salt according to claim 1 wherein R 14 is

lower alkyl carbonyl, lower arylalkyl carbonyl, aryl carbonyl,

wherein U is NH, or O.

9. The compound according to claim 1 wherein

R 14 is

10. A compound or a salt consisting of an anion and cation, wherein the compound or the cation of the salt is of the formula

wherein

R 1 and R 2 taken together with the carbon atoms to which they are attached form a pyridyl ring, said pyridyl ring may be unsubstituted or substituted with a lower alkyl group or an electron donating group;

Y is N;

Q 1 is CR 16 ;

R 16 is H or lower alkyl;

R 14 is

R 10 is OR 12 , lower alkyl, aryl, or aryl lower alkyl;

R 11 is OR 13 , lower alkyl, aryl, or aryl lower alkyl;

and R 10 and R 11 may optionally be connected by a bridging group selected from the consisting of O, S, NH, and (CH 2 ) m ;

m is 1-3; and

R 12 and R 13 are independently lower alkyl, aryl, or aryl lower alkyl.

11. The compound according to claim 1 wherein

wherein R 10 and R 11 are independently lower alkyl or aryl.

12. The compound according to claim 1 wherein

wherein R 11 and R 12 are independently lower alkyl or aryl.

13. The compound or salt according to claim 1 wherein the compound or the cation of the salt has the formula

wherein R 1 , R 2 , Q 2 and R 14 are as defined in claim 1 .

14. A compound or a salt consisting of an anion and cation, wherein the compound or the cation of the salt has the formula

wherein

A is N or CR 24 ;

D is CR 25 or N;

E is CR 26 or N;

G is CR 27 or N;

R 24 , R 25 , R 26 and R 27 are independently hydrogen, a lower alkyl group or an electron donating group, or R 25 and R 26 or R 24 and R 25 or R 26 and R 27 taken together with the carbon atoms to which they are respectively attached form an aryl ring;

wherein one of A, D, E and G, is N;

Y 1 is N;

Q 1 is CR 16 ;

R 16 is H or lower alkyl;

R 14 is a positively charged electron withdrawing group,

SO 2 R 17 , lower alkyl carbonyl, aryl carbonyl, lower alkyl aryl, or BLK 1 -AA 1

R 17 is aryl, aryl lower alkyl or lower alkyl;

AA 1 is an amino acid or peptide less a hydrogen atom on the N-terminus and an OH on the C-terminus;

BLK 1 is an amino protecting group,

R 10 is OR 12 , lower alkyl, aryl, aryl lower alkyl, lower cycloalkyl, lower cycloalkyl lower alkyl, heterocyclic, heterocyclic lower alkyl, lower cycloalkenyl, or lower cycloalkenyl lower alkyl;

R 11 is OR 13 , lower alkyl, aryl, aryl lower alkyl, lower cycloalkyl, lower cycloalkyl lower alkyl, heterocyclic, heterocyclic lower alkyl, lower cycloalkenyl or lower cycloalkenyl lower alkyl;

and R 10 and R 11 may optionally be connected by a bridging group selected from the group consisting of O, S, NR 30 , or (CHR 30 ) m , wherein each R 30 is independently lower alkyl or hydrogen and m is 1-3; and

R 12 and R 13 are independently lower alkyl, lower cycloalkyl, lower cycloalkyl lower alkyl, heterocyclic, heterocyclic lower alkyl, lower cycloalkenyl or lower cyclalkenyl lower alkyl;

ring A 1 and ring B are independently an aromatic ring containing 6 to 14 ring carbon atoms or cycloalkenyl or cycloalkyl, each containing 5 to 14 ring carbon atoms, and

R b1 , R c1 , R b2 , R c2 are independently hydrogen, lower alkyl or electron donating group;

T is (CHR 31 ), O, S or NR 31 ; and

R 31 is hydrogen or lower alkyl.

15. The compound or salt according to claim 14 where the compound or the cation has the formula

wherein

A is N or CR 24 ;

D is CR 25 or N;

E is CR 26 or N;

G is CR 27 or N;

R 24 , R 25 , R 26 and R 27 are independently hydrogen or lower alkyl;

wherein one of A, D, E and G, is N;

Y 1 is N;

Q 1 is CR 16 ;

R 16 is H or lower alkyl;

R 14 is a positively charged electron withdrawing group,

SO 2 R 17 , lower alkyl carbonyl, aryl carbonyl, loweralkyl aryl, or BLK 1 -AA 1

R 17 is aryl, aryl lower alkyl or lower alkyl;

AA 1 is an amino acid or peptide less a hydrogen atom on the N-terminus and an OH on the C-terminus;

BLK 1 is an amino protecting group,

R 10 is OR 12 , lower alkyl, aryl, aryl lower alkyl, lower cycloalkyl, lower cycloalkyl lower alkyl, heterocyclic, heterocyclic lower alkyl, lower cycloalkenyl, or lower cycloalkenyl lower alkyl;

R 11 is OR 13 , lower alkyl, aryl, aryl lower alkyl, lower cycloalkyl, lower cycloalkyl lower alkyl, heterocyclic, heterocyclic lower alkyl, lower cycloalkenyl or lower cycloalkenyl lower alkyl;

and R 10 and R 11 may optionally be connected by a bridging group selected from the group consisting of O, S, NR 30 , or (CHR 30 ) m , wherein each R 30 is independently lower alkyl or hydrogen and m is 1-3; and

R 12 and R 13 are independently lower alkyl, lower cycloalkyl, lower cycloalkyl lower alkyl, heterocyclic, heterocyclic lower alkyl, lower cycloalkenyl or lower cyclalkenyl lower alkyl;

ring A 1 and ring B are independently an aromatic ring containing 6 to 14 ring carbon atoms or cycloalkenyl or cycloalkyl, each containing 5 to 14 ring carbon atoms, and

R b1 , R c1 , R b2 , R c2 are independently hydrogen, lower alkyl or electron donating group;

T is (CHR 31 ), O, S or NR 31 ; and

R 31 is hydrogen or lower alkyl.

16. The compound according to claim 15 wherein R 14 is

wherein R 10 and R 11 , R b1 , R b2 , R c1 , R c2 are independently hydrogen or lower alkyl and T is O, CH 2 , NH or S and ring A 1 and ring B are independently an aromatic ring containing 6 to 14 ring carbon atoms.

17. The compound according to claim 1 wherein

wherein R 12 , R 11 , R b1 , R b2 , R c1 and R c2 are independently hydrogen or lower alkyl;

ring A 1 and ring B are independently phenyl; and

T is CH 2 , O, S or NH.

18. The compound according to claim 1 , wherein the compound is a salt, the cation of which has the formula

19. The compound according to claim 1 wherein the compound has the formula

wherein R b , R b1 , R c , are independently lower alkyl or hydrogen and T is CH 2 , NH, O or S.