Table 6. Overview of commonly used cysteine and selenocysteine protecting groups, their stability and standard cleavage conditions.
The most utilized protecting groups are marked in grey. A more complete overview of cysteine and selenocysteine protecting groups and cleavage conditions can be found in these reviews.155,156
| Chemistry | Protecting Group | Structure | Stability | Removal conditions |
|---|---|---|---|---|
| General Synthesis | Sulfur | |||
| Boc (Fmoc) |
4-Methylbenzyl (S-Meb) |
|
Base TFA |
HF 5% DMSO/TFA 60ºC |
| Boc (Fmoc) |
4-Methoxybenzyl (S-Mob) |
|
Base TFA |
HF TFMSA |
| Fmoc | Triphenylmethyl (S-Trt) |
|
Base | 1% TFA Tl(III) I2 |
| Fmoc | 2,4,6-Trimethoxybenzyl (S-Tmob) |
|
Base | 7% TFA/scavengers |
| Orthogonal Synthesis | ||||
| Boc | 9-Fluorenylmethyl (S-Fm) |
|
TFA HF |
Base |
| Boc | 3-Nitro-2-pyridylsulfenyl (S-Npys) |
|
TFA HF |
Reducing agents Thiols |
| Boc Fmoc |
Acetomidomethyl (S-Acm) |
|
Base TFA HF |
I2 Hg(II); Ag(II); Tl(II); |
| Boc Fmoc |
tert-Butylsulfenyl (S-S-tBu) |
|
TFA HF (partial) |
Reducing agents Thiols |
| Fmoc (Boc) |
tert-Butylmercapto (S-tBu) |
|
TFA Base |
5% DMSO/TFA 25ºC HF (20ºC) |
| Fmoc | 9H-Xanthen-9-yl (S-Xan) |
|
Base | 1% TFA/scavengers I2 Tl(III) |
| Selenium | ||||
| Boc | Benzyl (Se-Bzl) |
|
Base | Na/NH3 |
| Boc | 4-Methylbenzyl (Se-Meb) |
|
Base TFA |
HF |
| Boc Fmoc |
4-Nitro-benzyl (Se-pNB) |
|
Base TFA HF |
Zn, then I2
SnCl2, then I2 |
| Fmoc (Boc) |
Acetomidomethyl (Se-Acm) |
|
Base TFA HF (partial) |
I2 |
| Fmoc | 4-Methoxybenzyl (Se-Mob) |
|
Base | HF TFMSA or TMSBr TFA/DMSO/scavenger DTNP/TFA |