Description
Boc-N-methyl-L-leucine is the BOC (tert-butyloxycarbonyl) protected N-methylated leucine. The N-methylated amino acid is quite useful in the peptide synthesis, giving a lot of improved properties to peptide. Studies have shown that peptide containing N-methylated amino acids obtain increased proteolytic stability, increased membrane permeability, and altered conformation. The effects of N-methylated amino acids are quite important in the development of therapeutic peptide compound as well as in the assay of biological activity of some modified peptides. BOC group can be easily removed by treatment with strong acids such as trifluoroacetic acid.
Uses
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 suitability
reaction type: Boc solid-phase peptide synthesis
Biological Activity
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.
Synthesis
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.
References
https://en.wikipedia.org/wiki/Tert-Butyloxycarbonyl_protecting_group
http://pubs.acs.org/doi/abs/10.1021/cr030024zsrc=recsys&journalCode=chreay
