Protective groups acid/anisole

Deprotection of synthetic peptides. The protecting groups of synthetic peptides are generally removed by treatment with anhydrous HF and anisole. Most of the protecting groups can be removed by a low concentration of HF in dimethyl sulfide (1 3, v/v), and this method also decreases various side reactions caused by strong acids. Rate studies indicate that low-concentration HF cleavage is SN2, whereas an SN1 mechanism is involved in absolute HF. The mixture HF-S(CH3)2-p-cresol (25 65 10) is somewhat more potent. 

After the last amino acid had been incorporated, the A"-Boc protecting groups were removed before 1 g of the peptide-resin conjugate was treated with a mixture of 14 mL of HF, 1.5 mL of anisole, and 0.25 mL of methylethyl sulfide at —20 °C for 0.5 hour and at 0 °C for 0.5 hour. The HF was removed in vacuo at 0 °C, and the resulting peptide and resin mixture was washed twice with ether and twice with CHCI3 and ether alternately. The peptide was extracted five times with 2 M CH3COOH, and the extract was lyophilized. 

Solid-phase synthesis of a-/p-MSH were achieved in our group in 1980 (103), both using A -Boc chemistry. In the preparation of a-MSH, amino acids were coupled successively to valine-BHA resin with threefold excess of A -Boc amino acid and 2.4-fold excess of DCC in 1-15 hours. Removal of the A -Boc protecting group was achieved by a treatment of 45% TFA in DCM that contained 2% anisole. The side-chain protections were as follows Ser and Asp were protected by Bn groups ... 

Cresol, 5% thiocresol, 90% HF. In the HF deprotection of thioethers and many other protective groups, anisole serves as a scavenger for the liberated cation formed during the deprotection process. If cations liberated during this deprotection are not scavenged, they can react with other amino acid residues,... 

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