Uses
N-Boc-D-methionine is an N-Boc-protected form of D-Methionine (M260550). D-Methionine is an isomer of L-Methionine (M260440), and is known to be a cytoprotectant against Cisplatin (C499500), an anticancer agent. D-Methionine is also used to prevent noise- and drug-induced hearing loss, as well as hair loss (all of which may also be caused by Cisplatin or aminoglycosides).
Synthesis
(a) Preparation of tert-butoxycarbonyl-D-methionine: D-methionine (50.3 g, 0.34 mol) was dissolved in an aqueous solution (700 mL) containing sodium carbonate (71.5 g, 0.675 mol). To this solution was slowly added a solution of di-tert-butyl dicarbonate (81.0 g, 0.37 mol) in dioxane (250 mL), and the reaction mixture was stirred and reacted at room temperature for 16 hours. Upon completion of the reaction, it was diluted by adding water (1.5 L) and washed twice with ether (2 × 500 mL) to remove unreacted feedstock. Subsequently, the aqueous phase was acidified to pH 3 by addition of solid citric acid and the product was extracted with ethyl acetate (3 × 500 mL). The organic phases were combined, washed sequentially with water (2 × 500 mL) and saturated brine (500 mL), and finally dried with anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to afford tert-butoxycarbonyl-D-methionine as a colorless oil (87.6 g, 100% yield). The specific optical rotation of the product was [α]D +19.0° (c = 1%, methanol).
References
[1] Patent: US4863953, 1989, A
[2] Journal of the Chemical Society - Series Chemical Communications, 1989, # 22, p. 1740 - 1742
[3] Journal of Organic Chemistry, 1999, vol. 64, # 14, p. 5166 - 5175
[4] Journal of Medicinal Chemistry, 2011, vol. 54, # 13, p. 4815 - 4830
