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DOI: 10.1055/s-2008-1077887
Novel N,S-Phenacyl Protecting Group and Its Application for Peptide Synthesis
Publication History
Publication Date:
19 June 2008 (online)
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Abstract
The phenacyl group can be introduced onto amino and thio groups by N,S-alkylation reactions. Conversely, these groups are removed rapidly by employing magnesium in acetic acid. This protecting group was successfully applied to a short peptide synthesis of Boc-l-Cys-Gly-OMe.
Key words
protecting groups - alkyl halides - magnesium - peptides - thiols
- Supporting Information for this article is available online:
- Supporting Information
- 1
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References and Notes
Synthesis of Substrate
Materials 1-12; Typical Protection Procedure
To
an ice-cooled solution of amino or thio compound (5 mmol) in EtOAc
(20 mL) was added Et3N (0.55 g, 5.5 mmol) and phenacyl
bromide (1.1 g, 5.5mmol). After stirring at r.t. for 4 h, the reaction
mixture was diluted with EtOAc (25 mL). The organic layer was washed
with brine (10 mL), sat. NaHCO3 (10 mL), brine (2 × 10
mL), dried over Na2SO4, and filtered. The
filtrate was evaporated in vacuo and the crude product was purified
by silica gel chromatography using a mixture of PE-EtOAc.
Typical Deprotection Procedure
To
a solution of the protected substrate (2 mmol) in MeOH (15 mL) was
added AcOH (1.5 mL, 24 mmol) and Mg turnings (288 mg, 12 mmol).
The solution was stirred for 50-70 min (followed by TLC)
at r.t. The reaction mixture was filtered, and the filtrate was
concentrated in vacuo. The residue was diluted with 5% NaHCO3 (10
mL), EtOAc (2 10 mL), and combined organic solution.
The organic layer was washed with brine (2 10
mL), dried with Na2SO4, and filtered. The
filtrate was evaporated in vacuo. The crude product was purified
by silica gel chromatography using a mixture of PE-EtOAc.
N
-[
N
-(
tert
-Butoxycarbonyl)-
S
-(phenacylthio)cyste-inyl]glycine
Methyl Ester
(15)
Brown solid. ¹H
NMR (400 MHz, CDCl3): d = 1.44 (s, 9 H), 2.89-2.99
(m, 2 H), 3.73 (s, 3 H), 3.97-4.08 (m, 4 H), 4.49 (s, 1
H), 5.64 (d, J = 8.0
Hz), 7.30 (s, 1 H), 7.30-7.49 (m, 2 H), 7.57-7.61
(m, 1 H), 7.96-7.98 (m, 2 H) ppm. ¹³C
NMR (100 MHz, CDCl3): d = 195.2, 170.8, 169.8,
155.6, 135.2, 133.6, 128.7, 128.6, 80.3, 53.3, 52.3, 41.2, 38.3,
34.9, 28.2 ppm. ESI-MS: m/z = 411.2 [M + H]+,
433.1 [M + Na]+; [a]D
²0 -19.3
(c 1, MeOH). ESI-HRMS: m/z calcd
for [C19H26N2O6S + Na]+:
433.1409; found: 433.1411; for [C19H26N2O6S + H]+:
411.1590; found: 411.163.
N
-[
N
-(
tert
-Butoxycarbonyl)cysteinyl]glycine Methyl Ester (16)
Clear oil. ¹H
NMR (400 MHz, CDCl3): d = 1.46 (s, 9 H), 1,69
(dd, J = 7.6,
2.8 Hz), 2.73-2.75 (m, 1 H), 3.11-3.15 (m, 1 H),
3.76 (s, 3 H), 3.99-4.13 (m, 2 H), 4.42 (s, 1 H), 5.54
(d, J = 7.6
Hz, 1 H), 6.96 (s, 1 H) ppm. ¹³C NMR
(100 MHz, CDCl3): d = 170.5, 169.9, 155.4, 128.1
125.6, 80.9, 55.4, 52.4, 41.2, 28.2, 28.1, 26.9 ppm. ESI-MS: m/z = 293.1 [M + H]+,
315.1 [M + Na]+.