L-Tyrosine → HCID 87647670, compound
Reaction equation
F[P-](F)(F)(F)(F)F.[N:8]1(O[P+](N(C)C)(N(C)C)[N:19]([CH3:21])[CH3:20])[C:12]2[CH:13]=CC=C[C:11]=2N=N1.C[CH2:29][N:30](C(C)C)[CH:31]([CH3:33])[CH3:32].N[C@H](C(O)=O)[C@@H](C)O.[NH2:45][C@H:46](C(O)=O)[CH2:47][C:48]1C=CC(O)=[CH:50][CH:49]=1>>[CH3:13][CH:12]([CH3:11])[N:8]=[C:29]=[N:30][CH:31]([CH3:33])[CH3:32].[CH3:20][N:19]([C:48]1[CH:49]=[CH:50][N:45]=[CH:46][CH:47]=1)[CH3:21]Participants
Procedure
Ester bond between the pipecolic handle and side chain of amino acids was formed by using BOP/DIEA coupling for 90 minutes. Loading was determined by Fmoc titration on aliquots of resins 12, 14 and 18 for Thr, Ser and Tyr-functionalized resins, respectively (Table 3). Surprisingly, use of DIC/DMAP activation didn't give better result than BOP/DIEA mediated esterification. In a general manner, alcohol immobilization was less efficient than amine loading, according to Fmoc titration results, even when a negative malachite green test was observed. In particular with resins 12 and 14, obtained by the esterification of Fmoc-Thr-OMe and Fmoc-Ser-OMe side chains, experimental loadings were only 0.30 mmol/g and 0.32 mmol/g (i.e. 43% and 44% yield compared to maximum theoretical loading of 0.70 mmol/g). This result has to be put in perspective with the difficulty of loading primary alcohols on trityl-based resins giving experimental loading yields lower than 20% when compared to theoretical maximum loading (Barlos et al., 1988).
Workup
- customfor 90 minutes
Sources & evidence
- ORD record
- ord-85fe13396aa74778913eb48eb688ee5c
- Source dataset
- uspto-grants-2013_10
- Patent number
- US08546533B2
Reaction notes
Loading…