Reaction conditions, product formation and conversion for on-bead CuAAC cyclized peptides.
| Entry | Cu(i) (eq.) | Reagents (eq.)/solvent | Time (hrs) (inert gas) | Monomer % | Dimer | % conversiona |
|---|---|---|---|---|---|---|
| A | CuI (1.5) | Ascorbic acid (5), 20% piperidine/DMF | 15 | 51.1 | 13.0 | 87.4 |
| B | CuBr (1.0) | Sodium ascorbate (3)/2,6-lutidine (10)/DIEA (10)/MeCN : DMF (9.6 : 90.4) | 6 (argon) | 22.85 | 0e | 33.0 |
| C | CuI (0.5) | 2,6-Lutidine (2), DMSO : MeCN (20 : 80) | 16 (argon) | 3.8 | n.d.b,c | n.d.b,d |
a
With respect to linear starting material, the percentage of CuAAC products.
b
Could not be determined.
c
Mass corresponding to dimer could not be found.
d
Total yield could not be determined because of lack of dimer mass.
e
Linear peptide with one triazole formed instead of dimer; DMSO dimethyl sulfoxide, ACN acetonitrile, DMF dimethylformamide, Pip piperidine, DIEA diisopropylethylamine