Description
Fmoc-6-aminohexanoic acid can be used as a PROTAC linker in the synthesis of PROTACs and other conjugation applications. Fmoc-6-aminohexanoic acid is an alkane chian with terminal Fmoc-protected amine and carboxylic acid groups. The Fmoc group can be deprotected under basic condition to obtain the free amine which can be used for further conjugations. 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.
Synthesis
GENERAL STEPS: 389 mg (2.96 mmol) of 6-aminohexanoic acid was dissolved in 20 mL of a solvent mixture of acetone/water (1:1, v/v), 1.00 g (2.96 mmol) of 9-fluorenylmethyl-N-succinimidyl carbonate (FmocOSuc) and 250 mg (2.96 mmol) of sodium bicarbonate (NaHCO3) were added. The reaction suspension was stirred at room temperature for 3 hours. After completion of the reaction, acetone was removed by distillation under reduced pressure and 20 mL of dichloromethane (DCM) was added to the residue. Insoluble solids were removed by filtration. The organic phase was washed sequentially with 10 mL of 0.1 M hydrochloric acid (HCl) and 10 mL of water. The washed organic phase was dried with anhydrous sodium sulfate (Na2SO4), concentrated under reduced pressure to remove the solvent, and the residue was dried under vacuum to give 747 mg (71% yield) of the target product Fmoc-6-aminohexanoic acid as a colorless solid.
References
[1] Organic and Biomolecular Chemistry, 2018, vol. 16, # 39, p. 7139 - 7142
[2] Helvetica Chimica Acta, 1997, vol. 80, # 4, p. 1061 - 1072
[3] Beilstein Journal of Organic Chemistry, 2015, vol. 11, p. 493 - 498
[4] Bioconjugate Chemistry, 2018, vol. 29, # 9, p. 2909 - 2919
[5] Analytical Chemistry, 2005, vol. 77, # 10, p. 3301 - 3308
