Fluorous capping reagents and methods for peptide purification
Aspects of the present invention relate to compounds for preparing fluorocarbon compounds, methods for preparing fluorocarbon compounds, and methods for purifying a mixture of compounds. One aspect of the present invention relates to a trivalent iodonium fluorocarbon. The trivalent iodonium fluorocarbon compound of the invention is useful for attaching a fluorocarbon group to a compound that has a nucleophilic functional group. Another aspect of the present invention relates to a method of preparing a trivalent iodonium fluorocarbon. Another aspect of the present invention relates to a method of preparing a fluorocarbon by treating a compound bearing a nucleophilic functional group with a trivalent iodonium fluorocarbon compound. Another aspect of the present invention relates to a method or purifying a mixture comprising a first and a second compound by treating the mixture with a trivalent iodonium fluorocarbon to attach a fluorocarbon group to the second compound leaving the first compound unchanged, and purifying the mixture by fluorous-phase purification.
1. A compound represented by formula I:
wherein
R 1 is represented by formula
wherein R 8 is H, alkyl, or fluoroalkyl; R 9 is H, F, alkyl, or fluoroalkyl; R 10 is H or F; X is O, NR 5 , or S; m is 1-18 inclusive; p is 0-10 inclusive; q is 1-10 inclusive; r is 1, 2, 3, 4, 5, 6, 7, or 8; s is 1, 2, 3, 4, 5, or 6; and t is 0, 1, 2, 3, 4, 5, or 6;
R 2 is aryl, heteroaryl, alkenyl, or alkynyl;
R 3 and R 4 represent independently for each occurrence —SO 2 R 5 , —C(O)R 5 , —CO 2 R 5 , —C(O)N(R 6 ) 2 , —C(S)R 5 , —C(S)OR 5 , —C(S)N(R 6 ) 2 , or -aryl-(R 7 ) n ;
R 5 represents independently for each occurrence alkyl, fluoroalkyl, chloroalkyl, alkenyl, aryl, or aralkyl;
R 6 represents independently for each occurrence H, alkyl, fluoroalkyl, chloroalkyl, aryl, or aralkyl;
R 7 represents independently for each occurrence nitro, cyano, halogen, —SO 2 R 5 , —C(O)R 5 , —CO 2 R 5 , or —C(O)N(R 6 ) 2 ; and
n is independently 0, 1, 2, 3, 4, or 5 in accord with the rules of valence.
2. The compound of claim 1 , wherein R 1 is represented by formula:
wherein R 8 is H, alkyl, or fluoroalkyl; R 9 is H, F, alkyl, or fluoroalkyl; R 10 is H or F; and m is 1-18 inclusive.
3. The compound of claim 1 , wherein R 1 is represented by formula:
wherein R 8 is H; R 9 is H or F; R 10 is H or F; and m is 3-10 inclusive.
4. The compound of claim 1 , wherein R 1 is —CH 2 (CF 2 ) m CF 3 and m is 3-10 inclusive.
5. The compound of claim 1 , wherein R 1 is —CH 2 (CF 2 ) 6 CF 3 .
6. The compound of claim 1 , wherein R 1 is —CH 2 (CF 2 ) 8 CF 3 .
7. The compound of claim 1 , wherein R 2 is aryl.
8. The compound of claim 1 , wherein R 2 is optionally substituted phenyl.
9. The compound of claim 1 , wherein R 2 is phenyl.
10. The compound of claim 1 , wherein R 3 and R 4 represent independently for each occurrence —SO 2 R 5 , —C(O)R 5 , or —CO 2 R 5 .
11. The compound of claim 1 , wherein R 3 and R 4 represent independently for each occurrence —SO 2 R 5 .
12. The compound of claim 1 , wherein R 3 and R 4 represent independently for each occurrence —SO 2 R 5 , and R 5 is alkyl or fluoroalkyl.
13. The compound of claim 1 , wherein R 3 and R 4 are —SO 2 CF 3 .
14. The compound of claim 1 , wherein R 1 is —CH 2 (CF 2 ) 6 CF 3 and R 2 is phenyl.
15. The compound of claim 1 , wherein R 1 is —CH 2 (CF 2 ) 8 CF 3 and R 2 is phenyl.
16. The compound of claim 1 , wherein R 1 is —CH 2 (CF 2 ) 6 CF 3 ; R 2 is phenyl; and R 3 and R 4 are —SO 2 CF 3 .
17. The compound of claim 1 , wherein R 1 is —CH 2 (CF 2 ) 8 CF 3 ; R 2 is phenyl; and R 1 and R 4 are —SO 2 CF 3 .
18. A method of preparing a fluorocarbon compound, comprising the step of:
treating a compound comprising a nucleophilic functional group with a trivalent iodonium compound to generate a fluorocarbon compound, wherein said trivalent iodonium compound is represented by formula I:
wherein
R 1 represented by formula
wherein R 8 is H, alkyl, or fluoroalkyl; R 9 is H, F, alkyl, or fluoroalkyl; R 10 is H or F; X is O, NR 5 , or S; m is 1-18 inclusive; p is 0-10 inclusive; q is 1-10 inclusive; r is 1, 2, 3, 4, 5, 6, 7, or 8; s is 1, 2, 3, 4, 5, or 6; and t is 0, 1, 2, 3, 4, 5, or 6;
R 2 is aryl, heteroaryl, alkenyl, or alkynyl;
R 3 and R 4 represent independently for each occurrence —SO 2 R 5 , —C(O)R 5 , —CO 2 R 5 , —C(O)N(R 6 ) 2 , —C(S)R 5 , —C(S)OR 5 , —C(S)N(R 6 ) 2 , or -aryl-(R 7 ) n ;
R 5 represents independently for each occurrence alkyl, fluoroalkyl, chloroalkyl, aryl, or aralkyl;
R 6 represents independently for each occurrence H, alkyl, fluoroalkyl, chloroalkyl, aryl, or aralkyl;
R 7 represents independently for each occurrence nitro, cyano, halogen, —SO 2 R 5 , —C(O)R 5 , —CO 2 R 5 , or —C(O)N(R 6 ) 2 ; and
n is independently 0, 1, 2, 3, 4, or 5 in accord with the rules of valence.
19. A compound represented by formula I:
wherein
R 1 is fluoroheteroalkyl, fluorocycloalkyl, fluoroheterocycloalkyl, fluorocycloalkyl(C 1 -C 6 )alkyl, fluoroheterocycloalkyl(C 1 -C 6 )alkyl, (fluoroalkyl)aralkyl, fluoroaralkyl, or fluoroalkenyl(C 1 -C 6 )alkyl;
R 2 is aryl, heteroaryl, alkenyl, or alkynyl;
R 3 and R 4 represent independently for each occurrence —SO 2 R 5 , —C(O)R 5 , —CO 2 R 5 , —C(O)N(R 6 ) 2 , —C(S)R 5 , —C(S)OR 5 , —C(S)N(R 6 ) 2 , or -aryl-(R 7 ) n ;
R 5 represents independently for each occurrence alkyl, fluoroalkyl, chloroalkyl, alkenyl, aryl, or aralkyl;
R 6 represents independently for each occurrence H, alkyl, fluoroalkyl, chloroalkyl, aryl, or aralkyl;
R 7 represents independently for each occurrence nitro, cyano, halogen, —SO 2 R 5 , —C(O)R 5 , —CO 2 R 5 , or —C(O)N(R 6 ) 2 ; and
n is independently 0, 1, 2, 3, 4, or 5 in accord with the rules of valence.
20. The compound of claim 19 , wherein R 1 is fluoroheteroalkyl, fluorocycloalkyl(C 1 -C 6 )alkyl, fluoroheterocycloalkyl(C 1 -C 6 )alkyl, or fluoroaralkyl.
21. The compound of claim 19 , wherein R 1 is fluorocycloalkyl(C 1 -C 6 )alkyl.
22. A method of preparing a fluorocarbon compound, comprising the step of:
treating a compound comprising a nucleophilic functional group with a trivalent iodonium compound to generate a fluorocarbon compound, wherein said trivalent iodonium compound is represented by formula I:
wherein
R 1 is fluoroheteroalkyl, fluorocycloalkyl, fluoroheterocycloalkyl, fluorocycloalkyl(C 1 -C6)alkyl, fluoroheterocycloalkyl(C 1 -C 6 )alkyl, (fluoroalkyl)aralkyl, fluoroaralkyl, or fluoroalkenyl(C 1 -C 6 )alkyl;
R 2 is aryl, heteroaryl, alkenyl, or alkynyl;
R 3 and R 4 represent independently for each occurrence —SO 2 R 5 , —C(O)R 5 , —CO 2 R 5 , —C(O)N(R 6 ) 2 , —C(S)R 5 , —C(S)OR 5 , —C(S)N(R 6 ) 2 , or -aryl-(R 7 ) n ;
R 5 represents independently for each occurrence alkyl, fluoroalkyl, chloroalkyl, aryl, or aralkyl;
R 6 represents independently for each occurrence H, alkyl, fluoroalkyl, chloroalkyl, aryl, or aralkyl;
R 7 represents independently for each occurrence nitro, cyano, halogen, —SO 2 R 5 , —C(O)R 5 , —CO 2 R 5 , or —C(O)N(R 6 ) 2 ; and
n is independently 0, 1, 2, 3, 4, or 5 in accord with the rules of valence.