unified mild reaction conditions for c2-selective pd ... · s2 1. peptide arylation hplc data hplc...

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: ian.fairlamb@york.ac.uk; 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).