Description
Boc-8-aoc-oh can be used as a PROTAC linker in the synthesis of PROTACs. Boc-8-aoc-oh is an alkane chain with terminal carboxlic acid and Boc-protected amino groups. The terminal carboxylic acid can react with primary amine groups in the presence of activators (e.g. EDC, or HATU) to form a stable amide bond. The Boc group can be deprotected under mild acidic conditions to form the free amine.
Synthesis
GENERAL METHOD: Di-tert-butyl dicarbonate ((Boc)2O, 11.0 mmol) was dissolved in acetone (5 mL) and slowly added dropwise to a stirred acetone-water mixture (v:v 1:1, 20 mL) of 8-aminooctanoic acid (10.0 mmol) and triethylamine (Et3N, 20.0 mmol). The reaction mixture was stirred continuously at room temperature for 4-8 hours until complete consumption of 8-aminooctanoic acid was confirmed by thin layer chromatography (TLC) detection. Subsequently, the organic solvent was removed under reduced pressure and the remaining aqueous phase was adjusted to pH 4-5 with dilute hydrochloric acid. the aqueous phase was extracted with ethyl acetate (EtOAc), and the combined organic phases were washed with saturated saline and dried over anhydrous sodium sulfate (Na2SO4). Finally, the organic phase was concentrated under reduced pressure and the product was freeze-dried at -80 °C to obtain Boc-8-aminooctanoic acid.
References
[1] Journal of Asian Natural Products Research, 2017, vol. 19, # 3, p. 272 - 298
[2] ACS Medicinal Chemistry Letters, 2013, vol. 4, # 4, p. 402 - 407
[3] Chemical and Pharmaceutical Bulletin, 2000, vol. 48, # 12, p. 1964 - 1972
[4] Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 718 - 738
[5] Journal of Medicinal Chemistry, 2001, vol. 44, # 26, p. 4696 - 4703
