Fmoc-Arg(Pbf)-OH CAS 154445-77-9

Fmoc-Pbf-Arginine CAS No.: 154445-77-9

Properties Melting point: 132 °C Optical rotation: -5.5 º (c=1, DMF) Density: 1.37±0.1 g/cm³ (Predicted) Storage condition: Store at -15 °C to -25 °C Solubility: Slightly soluble in DMF, DMSO and methanol Form: Solid pKa: 3.83±0.21 (Predicted) Color: White to off-white Optical Rotation [α]/D: -5.5±1.0°, c=1 in DMF BRN: 8302671

Application & Synthesis Method Description: Arginine is an amino acid. For research use in peptide synthesis, amino group and guanidino group of arginine need protection to reduce side reactions. Fmoc-Pbf-arginine is an arginine derivative, with amino group protected by Fmoc (9-fluorenylmethoxycarbonyl) and guanidino group protected by Pbf (2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran-5-sulfonyl).

Application: Used for peptide synthesis research.

Synthesis Route: (1) Esterification a1. Add 100 L anhydrous ethanol into pre-dried 300 L reactor, cool to -5～-10 ℃ with ice brine, dropwise add 13 L thionyl chloride. b1. Add 21.5 kg D-Arg·HCl, stop ice brine cooling, warm naturally to room temperature and react for 24 h. c1. Heat to 35 ℃ for reaction, monitor by TLC, reaction completes in about 48 h. d1. Concentration: Concentrate under reduced pressure to obtain Arg·Oet·2HCl oily intermediate.

(2) Boc group introduction a2. Add 150 L water and 25.2 kg sodium bicarbonate into 300 L reactor under stirring; slowly add the Arg·Oet·2HCl oil, then add 30 L tetrahydrofuran, add 26.2 kg (Boc)₂O in batches, stir at room temperature and track by TLC until raw material is consumed. b2. Acidification: Adjust pH to 3-4 after reaction, extract with petroleum ether / ethyl acetate (50 L:25 L). c2. Saturate with salt, adjust pH back to 6-7, extract target product with ethyl acetate, wash organic phase with saturated brine. d2. Drying: Add 60 kg anhydrous sodium sulfate into ethyl acetate organic phase, dry for 8 h. e2. Purification and concentration: Filter out sodium sulfate, concentrate ethyl acetate phase under reduced pressure to get Boc-ArgOet·HCl oil.

(3) Pbf group introduction a3. Add Boc-ArgOet·HCl obtained from step 2, 31.9 kg Pbf-Cl, 200 L acetone and 41.7 kg potassium carbonate into 300 L reactor, add a small amount of water while stirring, keep temperature at 40-45 ℃, monitor reaction by TLC until Boc-ArgOet·HCl is fully consumed. b3. Filter to remove insoluble solids, distill acetone under reduced pressure to obtain Boc-Arg(Pbf)Oet oil for next use.

(4) Boc deprotection a4. Add 120 L 3N HCl/ethyl acetate solution into dry 300 L reactor, add Boc-Arg(Pbf)Oet oil under stirring, maintain 10-15 ℃ and stir at room temperature. b4. After deprotection completes, wash with water to transfer product into aqueous phase, add sodium carbonate to adjust aqueous pH to 7.

(5) Saponification a5. Add 100 L 95% ethanol into aqueous phase from step (4) under stirring, dropwise add 10 N NaOH aqueous solution to adjust pH to 11-12 for saponification. b5. After saponification, adjust pH to 7 with 6 N HCl, cool to -10～0 ℃ for freeze crystallization. Centrifuge, stir and wash solid with ethyl acetate, centrifuge and collect solid. Recrystallize to obtain H-Arg(Pbf)OH solid.

(6) Synthesis of Fmoc-Pbf-Arginine a6. Add H-Arg(Pbf)-OH, 120 L water and THF into reactor, adjust pH to 8.5 with Na₂CO₃. b6. Gradually add Fmoc-Osu (Fluorenylmethyloxycarbonyl succinimide), control temperature 15-20 ℃ and pH 8-9 to consume Arg(Pbf), avoid excess Fmoc-Osu. Track reaction by TLC, reaction lasts 6 h after feeding Fmoc-Osu. c6. Purification: Extract with petroleum ether / ethyl acetate (2:1). Acidify aqueous phase with HCl to pH=3 and stir for 2 h at 0-10 ℃. Extract product with ethyl acetate, wash organic phase with saturated brine until pH reaches 6. Dry with anhydrous sodium sulfate, filter, concentrate filtrate under reduced pressure, vacuum dry to get final solid product. Product purity: 99.6%, maximum single impurity: 0.09%, L-isomer: 0.15%.

Safety Information Hazard symbol: Xi Risk codes: 36/37/38 Safety statements: 26-36 WGK Germany: 1 HS code: 29359090 Hazard class: IRRITANT Storage class: 11 - Combustible solid MSDS: Available upon request