Uses
Fmoc-Tle-OH is a versatile reactant used in the discovery of potent antagonists of antiapoptotic protein X-linked inhibitor of apoptosis (XIAP) for treatment of cancer. It is also used as reactant in the preparation of phosphino dipeptide derivatices as ligand in copper-phosphine catalyst for asymmetric conjugate addition of alkylzinc reagents to unsaturated ketones.
Synthesis
General procedure for the synthesis of Fmoc-L-tert-leucine from L-tert-leucine and 9-fluorenylmethyl chloroformate: a 500 mL reaction flask was taken and to it was added L-tert-leucine (5.1 g, 38.6 mmol), dioxane (40 mL), and 10% sodium carbonate solution (100 mL). The reaction flask was placed in an ice bath and a dioxane solution (100 mL) of methyl chloroformate-9-fluorenyl (10.0 g, 38.6 mmol) was slowly added through a dropping funnel under mechanical stirring. After dropwise addition, the solution was gradually returned to room temperature and stirring was continued overnight. After completion of the reaction, 100 mL of water was added and extracted three times with 50 mL of ether, retaining the aqueous phase. The aqueous phase was cooled in an ice bath and the pH was adjusted slowly to 1 by adding 1 M dilute hydrochloric acid. subsequently, the aqueous solution was extracted three times with 50 mL of ethyl acetate. The organic phases were combined, dried with anhydrous magnesium sulfate, filtered and concentrated to dryness to give the intermediate Fmoc-L-tert-leucine (14.3 g, 96% yield).
References
[1] Patent: CN106588987, 2017, A. Location in patent: Paragraph 0195; 0196; 0197
[2] Angewandte Chemie - International Edition, 2013, vol. 52, # 45, p. 11846 - 11851
[3] Angew. Chem., 2013, vol. 125, # 45, p. 12062 - 12067,6
[4] Chemistry - A European Journal, 2014, vol. 20, # 21, p. 6526 - 6531
[5] Patent: WO2018/145021, 2018, A1. Location in patent: Page/Page column 134
