N-9-fluorenylmethoxycarbonyl-Se-4-methoxybenzylselenocysteine

Chemical Properties

White or off-white powder

Uses

peptide synthesis

General Description

Building block for the introduction of selenocysteine during Fmoc SPPS [1-3]. Selenocysteine derivatives can undergo enantiomerization during coupling and can form dehydroalanine and β-piperidinylalanine containing side products during subsequent chain elongation [3]. Therefore, activation methods, such as HBTU or PyBOP which involve the addition of a tertiary, base should be avoided for addtion of the Sec and all subsequent residues.



Cleavage and side-chain deprotection of Sec-containing peptides can be effected using tFA-m-cresol-thioanisole-EDT-water (80:5:5:5:5)[2] or TFA-water-DCM-TIS (89:5:51) at 4 °C [3]. As the Se-pMeOBzl bond is stable to TFA, these emthods result in formation of the corresponding Sev(pMeOBzl) peptide.



Peptides containing two Sec(pMeOBzl) residues can be oxidized directly to the corresponding selenocystinyl peptides by treatment with 5-10% DMSO in TFA [1-3].

reaction suitability

reaction type: Fmoc solid-phase peptide synthesis

Synthesis

The general procedure for the synthesis of N-fluorenylmethoxycarbonyl-3-[[(4-methoxyphenyl)methyl]selenyl]-L-alanine from the compound (CAS: 1365284-58-7) was as follows: a mixture of raw material 14 (790 mg, 1.5 mmol) and trimethyltin hydroxide (989 mg, 5.5 mmol) was dissolved in anhydrous 1,2-dichloroethane ( 15 mL). The reaction mixture was stirred at 35 °C overnight. Upon completion of the reaction, the mixture was filtered and the filtrate was evaporated to remove the solvent. The resulting crude product was purified by silica gel column chromatography with an eluent ratio of hexane:EtOAc = 2:1 to 0:1 to give product 15 as a colorless oil or white solid (702 mg, 91% yield). The spectral data of product 15 were in agreement with those reported in the literature37 and its purity was confirmed by 1H NMR and HPLC analyses.1H NMR (CDCl3) data were as follows: δ 2.98 (2H, m, β-H), 3.78 (3H, s, p-OMe), 3.79 (2H, s, CH2), 4.26 (1H, t, JHH 6.8 Hz, Fmoc-CH ), 4.45 (1H, d, JHH 6.7 Hz, Fmoc-CH2), 4.70 (1H, m, α-H), 5.54 (1H, d, JHH 7.8 Hz, NH), 6.83 (2H, d, JHH 8.4 Hz, ArH), 7.20 (2H, d, JHH 8.3 Hz, ArH), 7.33 (2H, m, ArH ), 7.42 (2H, m, ArH), 7.63 (2H, t, JHH 6.7 Hz, ArH), 7.78 (2H, m, ArH).13C NMR (CDCl3) data were as follows: δ 25.1, 27.7, 47.1, 53.6, 55.3, 67.3, 114.1, 120.0, 125.1, 127.1, 127.8, 130.0, 141.3, 143.6, 158.7. 77Se NMR (CDCl3) data are as follows: δ 216.7.

References

[1] Journal of Peptide Science, 2012, vol. 18, # 3, p. 155 - 162
[2] Arkivoc, 2016, vol. 2017, # 2, p. 260 - 271