unified mild reaction conditions for c2-selective pd ... · s2 1. peptide arylation hplc data hplc...
TRANSCRIPT
S1
Supporting Information
for:
Unified mild reaction conditions for C2-selective Pd-
catalysed tryptophan arylation, including tryptophan-
containing peptides
Alan J. Reay, Thomas J. Williams and Ian J. S. Fairlamba
a Department of Chemistry, University of York, Heslington, York, YO10 5DD.
Email: [email protected]; Tel: 0044 (0)1904 324091.
Contents
1. Peptide Arylation HPLC Data............................................................................. S2
2. UV-Visible Spectroscopic Data ........................................................................ S11
3. NMR spectroscopic data .................................................................................. S18
Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry.This journal is © The Royal Society of Chemistry 2015
S2
1. Peptide Arylation HPLC Data
HPLC data for arylated peptides 4 and 6 are given in our preliminary communication on this
work.1
Arylated product of Ac-AlaTrpAla-OH 7, 8
HPLC-ESI-MS chromatogram (BPC) of the crude reaction material from Method A (arylated
tryptophan donated Trp*, diarylated tryptophans donated Trp**, dihydroxylated byproducts
donated Trp‡).
ESI-MS of the crude reaction material.
1 T. J. Williams, A. J. Reay, A. C. Whitwood and I. J. S. Fairlamb, Chem. Commun., 2014,
50, 3052.
Ac-AlaTrp*Ala-OH, m/z 465, 54%
Ac-AlaTrp**Ala-OH,
m/z 541, 8%
Ac-AlaTrp‡Ala-OH, m/z 497, 37%
S3
S4
HPLC-ESI-MS chromatogram (BPC) of the crude reaction material from Method B (arylated
tryptophan donated Trp*, starting material donated Trp).
ESI-MS of the crude reaction material.
Ac-AlaTrp*Ala-OH, m/z 465, 48%
Ac-AlaTrpAla-OH,
m/z 465, 52%
[MesPhI]+, m/z 323
S5
S6
S7
Arylated product of Ac-SerGlyTrpAla-OH 9, 10.
HPLC-ESI-MS chromatogram (BPC) of the crude reaction material from Method A (arylated
tryptophan donated Trp*, dihydroxylated byproducts donated Trp‡).
ESI-MS of the crude reaction material.
Ac-SerGlyTrp*Ala-OH, m/z 560, 42% Ac-SerGlyTrp‡Ala-OH,
m/z 570, 57%
S8
HPLC-ESI-MS chromatogram (BPC) of the crude reaction material from Method B (arylated
tryptophan donated Trp*, starting material donated Trp).
ESI-MS of the crude reaction material.
Ac-SerGlyTrp*Ala-OH, m/z 560, 56%
Ac-SerGlyTrpAla-OH,
m/z 560, 44% [MesPhI]+, m/z 323
S9
S10
S11
2. UV-Visible Spectroscopic Data
UV-visible spectroscopic analysis of 12b (concentration range in legend, mol dm-3)
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
270 370 470 570 670
Ab
so
rban
ce
Wavelength / nm
0.0001
0.00008
0.00006
0.00004
0.00002
y = 9725.4x R² = 1
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
0 0.00002 0.00004 0.00006 0.00008 0.0001
Ab
so
rban
ce
Concentration / mol dm-3
S12
UV-visible spectroscopic analysis of 13 (concentration range in legend, mol dm-3)
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
270 370 470 570 670
Ab
so
rban
ce
Wavelength / nm
0.0001
0.00008
0.00006
0.00004
0.00002
y = 10138x R² = 0.9984
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
0 0.00002 0.00004 0.00006 0.00008 0.0001
Ab
so
rban
ce
Concentration / mol dm-3
S13
UV-visible spectroscopic analysis of 14a (concentration range in legend, mol dm-3)
0
0.2
0.4
0.6
0.8
1
1.2
270 370 470 570 670
Ab
so
rban
ce
Wavelength / nm
0.00005
0.00004
0.00003
0.00002
0.00001
y = 20684x R² = 0.9994
0
0.2
0.4
0.6
0.8
1
1.2
0 0.00001 0.00002 0.00003 0.00004 0.00005
Ab
so
rban
ce
Concentration / mol dm-3
S14
UV-visible spectroscopic analysis of 14b (concentration range in legend, mol dm-3)
0
0.2
0.4
0.6
0.8
1
1.2
1.4
270 370 470 570 670
Ab
so
rban
ce
Wavelength / nm
0.0001
0.00008
0.00006
0.00004
0.00002
y = 12188x R² = 0.9996
0
0.2
0.4
0.6
0.8
1
1.2
1.4
0 0.00002 0.00004 0.00006 0.00008 0.0001
Ab
so
rban
ce
Concentration / mol dm-3
S15
UV-visible spectroscopic analysis of 15 (concentration range in legend, mol dm-3)
0
0.1
0.2
0.3
0.4
0.5
0.6
270 370 470 570 670
Ab
so
rban
ce
Wavelength / nm
0.0001
0.00008
0.00006
0.00004
0.00002
y = 5733.7x R² = 0.9977
0
0.1
0.2
0.3
0.4
0.5
0.6
0 0.00002 0.00004 0.00006 0.00008 0.0001
Ab
so
rban
ce
Concentration / mol dm-3
S16
UV-visible spectroscopic analysis of 16a (concentration range in legend, mol dm-3)
0
0.2
0.4
0.6
0.8
1
1.2
270 370 470 570 670
Ab
so
rban
ce
Wavelength / nm
0.00005
0.00004
0.00003
0.00002
0.00001
y = 20467x R² = 0.9998
0
0.2
0.4
0.6
0.8
1
1.2
0 0.00001 0.00002 0.00003 0.00004 0.00005
Ab
so
rban
ce
Concentration / mol dm-3
S17
UV-visible spectroscopic analysis of 16b (concentration range in legend, mol dm-3)
0
0.2
0.4
0.6
0.8
1
1.2
270 370 470 570 670
Ab
so
rban
ce
Wavelength / nm
0.00013
0.000104
0.000078
0.000052
0.000026
y = 8711.5x R² = 0.9995
0
0.2
0.4
0.6
0.8
1
1.2
0 0.00002 0.00004 0.00006 0.00008 0.0001 0.00012 0.00014
Ab
so
rban
ce
Concentration / mol dm-3
S18
3. NMR spectroscopic data
NMR spectra for compounds 2b, 2e, 3, 4 and 2-Acetamidoacetic acid are given in our
preliminary communication on this work.1
S19
Methyl (2S)-2-amino-3-(1H-indol-3-yl)propanoate hydrochloride
1H NMR spectrum (400 MHz, CD3OD).
13C NMR spectrum (400 MHz, CD3OD).
S20
Methyl (2S)-2-acetamido-3-(1H-indol-3-yl)propanoate, 1a
1H NMR spectrum (400 MHz, CDCl3).
13C NMR spectrum (400 MHz, CDCl3).
S21
Methyl (2S)-2-{[(tert-butoxy)carbonyl]amino}-3-(1H-indol-3-yl)propanoate, 1b
1H NMR spectrum (400 MHz, CDCl3).
13C NMR spectrum (400 MHz, CDCl3).
S22
Methyl (2S)-3-(1H-indol-3-yl)-2-(trifluoroacetamido)propanoate, 1c
1H NMR spectrum (400 MHz, CDCl3).
13C NMR spectrum (400 MHz, CDCl3).
S23
19F NMR spectrum (376 MHz, CDCl3).
S24
Methyl (2S)-2-acetamido-3-(2-phenyl-1H-indol-3-yl)propanoate, 2a
1H NMR spectrum (400 MHz, CDCl3).
13C NMR spectrum (400 MHz, CDCl3).
S25
Methyl (2S)-2-acetamido-3-[2-(4-methoxyphenyl)-1H-indol-3-yl]propanoate, 2c
1H NMR spectrum (400 MHz, CDCl3).
13C NMR spectrum (400 MHz, CDCl3).
S26
Methyl (2S)-3-[2-(4-fluorophenyl)-1H-indol-3-yl]-2-acetamidopropanoate, 2d
1H NMR spectrum (400 MHz, CDCl3).
13C NMR spectrum (400 MHz, CDCl3).
S27
19F NMR spectrum (376 MHz, CDCl3).
S28
Methyl (2S)-2-acetamido-3-[2-(2,4,6-trimethylphenyl)-1H-indol-3-yl]propanoate, 2f
1H NMR spectrum (400 MHz, CDCl3).
13C NMR spectrum (400 MHz, CDCl3).
S29
Phenyl(2,4,6-trimethylphenyl)iodonium trifluoromethanesulfonate,11a
1H NMR spectrum (400 MHz, CDCl3).
13C NMR spectrum (400 MHz, CDCl3).
S30
Phenyl(2,4,6-triisopropylphenyl)iodonium trifluoromethanesulfonate, 11b
1H NMR spectrum (400 MHz, CDCl3).
13C NMR spectrum (400 MHz, CDCl3).
S31
Methyl (2S)-3-(2-phenyl-1H-indol-3-yl)-2-(trifluoroacetamido)propanoate, 12a
1H NMR spectrum (400 MHz, CDCl3).
13C NMR spectrum (400 MHz, CDCl3).
S32
19F NMR spectrum (376 MHz, CDCl3).
S33
Methyl (2S)-3-(2-phenyl-1H-indol-3-yl)-2-(trifluoroacetamido)propanoate, 12b
1H NMR spectrum (400 MHz, CDCl3).
13C NMR spectrum (400 MHz, CDCl3).
S34
19F NMR spectrum (376 MHz, CDCl3).
S35
2-(Trifluoroacetamido)acetic acid
1H NMR spectrum (400 MHz, CD3OD).
13C NMR spectrum (400 MHz, CD3OD).
S36
19F NMR spectrum (376 MHz, CD3OD).
S37
Methyl (2S)-3-(1H-indol-3-yl)-2-[2-(trifluoroacetamido)acetamido]propanoate, 13
1H NMR spectrum (400 MHz, CDCl3).
13C NMR spectrum (400 MHz, CDCl3).
S38
19F NMR spectrum (376 MHz, CDCl3).
S39
Methyl (2S)-3-(2-phenyl-1H-indol-3-yl)-2-[2-(trifluoroacetamido)acetamido]propanoate, 14a
1H NMR spectrum (400 MHz, CDCl3).
13C NMR spectrum (400 MHz, CDCl3).
S40
19F NMR spectrum (376 MHz, CDCl3).
S41
Methyl (2S)-2-[2-(trifluoroacetamido)acetamido]-3-[2-(2,4,6-trimethylphenyl)-1H-indol-3-
yl]propanoate, 14b
1H NMR spectrum (400 MHz, CDCl3).
13C NMR spectrum (400 MHz, CDCl3).
S42
19F NMR spectrum (376 MHz, CDCl3).
S43
(2R)-4-Methyl-2-(trifluoroacetamido)pentanoic acid
1H NMR spectrum (400 MHz, CD3OD).
13C NMR spectrum (400 MHz, CD3OD).
S44
19F NMR spectrum (376 MHz, CD3OD).
S45
Methyl (2S)-3-(1H-indol-3-yl)-2-[(2R)-4-methyl-2-trifluoroacetamido)pentanamido]
propanoate, 15
1H NMR spectrum (400 MHz, CDCl3).
13C NMR spectrum (400 MHz, CDCl3).
S46
19F NMR spectrum (376 MHz, CDCl3).
S47
Methyl (2S)-2-[(2R)-4-methyl-2-(trifluoroacetamido)pentanamido]-3-(2-phenyl-1H-indol-3-
yl)propanoate, 16a
1H NMR spectrum (400 MHz, CDCl3).
13C NMR spectrum (400 MHz, CDCl3).
S48
19F NMR spectrum (376 MHz, CDCl3).
S49
Methyl (2S)-2-[(2R)-4-methyl-2-(trifluoroacetamido)pentanamido]-3-[2-(2,4,6-
trimethylphenyl)-1H-indol-3-yl]propanoate, 16b
1H NMR spectrum (400 MHz, CDCl3).
13C NMR spectrum (400 MHz, CDCl3).
S50
19F NMR spectrum (376 MHz, CDCl3).