On the basis of the above logics, we tuned the distance parameter to improve H2BK108-selectivity through optimizing the structure of catalyst 2. We decreased the carbon chain length of the side chain at residue-7 from n = 4 (Lys) to n = 1-3 (diaminopropionic acid (Dap): 5, diaminobutyric acid (Dab): 6, and ornithine (Orn): 7) (Figure ). Remarkably, H2BK108 acylation yield using catalyst 6 or 7 was higher than that using catalyst 2, whereas H2BK116 acylation yield was comparable or decreased (Figure ). In contrast, H2BK108-selectivity of catalyst 5 was significantly lower than other catalysts (Figure ), suggesting that H2BK108 was outside CER of catalyst 5.