Lysine-glutamic acid dipeptide derivatives
The invention relates to compounds of the formula I. The compounds of formula I are versatile peptide intermediates for the solid phase peptide synthesis (SPPS) of peptide drugs which comprise a Glu-fatty alkyl side chain building block attached to a Lys-part of the peptide chain.
1. A compound of the formula
wherein,
R 1 is t-butyl,
R 2 is hydrogen or an ester protecting group,
R 3 is hydrogen or an amino protecting group, and
R 4 is C 12-20 -alkyl,
and enantiomers, diastereomers and salts thereof.
2. The compound of claim 1 wherein, the ester protecting group is selected from C 1-4 -alkyl, optionally substituted with phenyl, C 2-4 -alkenyl, piperidinyl or dimethylaminoboranyl.
3. The compound of claim 1 , wherein
R 2 is hydrogen or C 2-4 -alkenyl.
4. The compound of claim 1 , wherein R 2 is hydrogen or allyl.
5. The compound of claim 1 , wherein R 3 is 9H-fluoren-9-ylmethoxycarbonyl.
6. The compound of claim 1 , wherein R 4 is C 14-16 -alkyl.
7. A compound of the formula
wherein,
R 1 is t-butyl,
R 2 is hydrogen or an ester protecting group,
R 3 is hydrogen or an amino protecting group, and
R 4 is C 12-20 -alkyl,
and salts thereof.
8. The compound of claim 7 , wherein,
R 2 is hydrogen, R 3 is 9H-fluoren-9-ylmethoxycarbonyl and R 4 is C 15 -alkyl; or
R 2 is allyl, R 3 is 9H-fluoren-9-ylmethoxycarbonyl and R 4 is C 15 -alkyl.
9. The compound of claim 7 , wherein,
R 2 is hydrogen, R 3 is 9H-fluoren-9-ylmethoxycarbonyl and R 4 is pentadecyl; or
R 2 is allyl, R 3 is 9H-fluoren-9-ylmethoxycarbonyl and R 4 is pentadecyl.
10. The compound of claim 1 , wherein R 2 is hydrogen, R 3 is 9H-fluoren-9-ylmethoxycarbonyl and R 4 is C 15 -alkyl.
11. The compound of claim 1 , wherein R 2 is allyl, R 3 is 9H-fluoren-9-ylmethoxycarbonyl and R 4 is C 15 -alkyl.
12. The compound of claim 1 , wherein R 2 is hydrogen, R 3 is 9H-fluoren-9-ylmethoxycarbonyl and R 4 is pentadecyl.
13. The compound of claim 1 , wherein R 2 is allyl, R 3 is 9H-fluoren-9-ylmethoxycarbonyl and R 4 is pentadecyl.
14. A compound of the formula
wherein,
R 1 is t-butyl,
R 2 is hydrogen or an ester protecting group,
R 3 is hydrogen or an amino protecting group, and
R 4 is C 12-20 -alkyl,
and salts thereof.
15. The compound of claim 14 , wherein,
R 2 is hydrogen, R 3 is 9H-fluoren-9-ylmethoxycarbonyl and R 4 is C 15 -alkyl; or
R 2 is allyl, R 3 is 9H-fluoren-9-ylmethoxycarbonyl and R 4 is C 15 -alkyl.
16. The compound of claim 14 , wherein,
R 2 is hydrogen, R 3 is 9H-fluoren-9-ylmethoxycarbonyl and R 4 is pentadecyl; or
R 2 is allyl, R 3 is 9H-fluoren-9-ylmethoxycarbonyl and R 4 is pentadecyl.
17. The compound of claim 1 , wherein R 2 is allyl.
18. The compound of claim 7 , wherein R 2 is hydrogen or allyl.
19. The compound of claim 7 , wherein R 3 is 9H-fluoren-9-ylmethoxycarbonyl.
20. The compound of claim 7 , wherein R 4 is C 14-16 -alkyl.
21. The compound of claim 7 wherein R 2 is allyl.
22. The compound of claim 14 , wherein R 2 is hydrogen or allyl.
23. The compound of claim 14 , wherein R 3 is 9H-fluoren-9-ylmethoxycarbonyl.
24. The compound of claim 14 , wherein R 4 is C 14-16 -alkyl.
25. The compound of claim 14 , wherein R 2 is allyl.