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Boc-N-methyl-L-leucine, is an amino acid building block used in peptide synthesis. With a growing peptide drug market the fast, reliable synthesis of peptides is of great importance.

reaction type: Boc solid-phase peptide synthesis

Boc-N-methyl-L-leucine is a peptidyl nucleobase that has been shown to inhibit tumor cell growth and induce tumor regression in animal models. It is an amide of leucine and the antibiotic aminouracil, which is a guanine analogue. Boc-N-methyl-L-leucine has also shown to inhibit tumor growth by inhibiting mitochondrial membrane potential, which may lead to cell death in cancer cells. This compound has been shown to be effective against both solid tumors and leukemia cell lines. Boc-N-methyl-L-leucine also inhibits the proliferation of human prostate cancer cells by blocking the synthesis of nucleic acids and proteins.

To a solution of Boc-L-leucine (5.0 g, 21.6 mmol) in tetrahydrofuran (THF, 73 mL) at 0 °C was added sodium hydride (NaH, 60% dispersion in mineral oil, 10.0 g, 0.13 mol). After stirring at 0 °C for 30 min, iodomethane (MeI, 4.1 mL, 66.0 mmol) and N,N-dimethylformamide (DMF, 3.7 mL) were added sequentially. The reaction mixture was continued to be stirred at 0 °C for 30 min, followed by 4 h at room temperature. Upon completion of the reaction, the reaction was quenched with deionized water (50 mL). The mixture was extracted with ethyl acetate (EtOAc, 2 x 100 mL). The aqueous phase was acidified to pH 5 with 10% aqueous potassium bisulfate (KHSO4) and extracted again with ethyl acetate. All the ethyl acetate extracts were combined, washed with 5% sodium dithionite (Na2S2O4) solution and saturated brine in turn, dried with anhydrous sodium sulfate (Na2SO4), filtered and concentrated under reduced pressure to give Boc-N-methyl-L-leucine (5.2 g, 98% yield) as a colorless oil.