Table 1. Condition optimization of N-terminal alkylation ^{a , b , c , f} .

Entry	Buffer	pH	(3a + 3a′) (%)	N-Selectivity d	3a′′ (%)
1	A	3.3	49	>99 : 1	38
2	B	4.0	58	98 : 2	30
3	A	6.0	60	95 : 5	22
4	B	6.1	78	>99 : 1	18
5	C	7.4	60	80 : 20	20
6	D	9.7	35	73 : 27	7
7	C	10.0	50	90 : 10	10
8 e	B	6.1	60	>99 : 1	16

^aThe reaction was performed with 2.7 μmol peptide, 5.4 μmol, benzaldehyde (0.5 M in DMSO), and 13.5 μmol NaBH₃CN in 300 μL aqueous solvent at room temperature for 6 h.

^bBuffer A is 25 mmol L^–1 acetic acid buffer; buffer B is 25 mmol L^–1 citric acid buffer; buffer C is 25 mmol L^–1 phosphate buffer; buffer D is 25 mmol L^–1 borate buffer.

^cThe conversion was calculated by area of the corresponding peak under 280 nm UV detection of the reaction system.

^dDetermined by MS/MS analysis.

^e1.5 equivalents benzaldehyde was used.

^fSee ESI Table S1 for more condition screening data.