Effect of capping groups at the N-and C-termini on the ... · 1 Supporting information Effect of...

1

Supporting information

Effect of capping groups at the N-and C-termini on the

conformational preference of α,β-peptoids.

Emiliana De Santis,a Thomas Hjelmgaard,

b,c Cécile Caumes,

b,c Sophie Faure,

b,c Bruce D. Alexander,

d

Simon J. Holder,e Giuliano Siligardi,

f Claude Taillefumier,

b,c* Alison A. Edwards.

a*

a Medway School of Pharmacy, Universities of Kent and Greenwich at Medway, Central Avenue,

Chatham Maritime, Kent, ME4 4TB, United Kingdom. Fax: +44 (0)1634 883927; Tel: +44 (0)1634 202947; [email protected]

bClermont Université, Université Blaise Pascal, Laboratoire SEESIB, BP 10448, F-63000 Clermont-

Ferrand cCNRS, UMR 6504, Laboratoire SEESIB, F-63177 AUBIERE cedex, France. Fax: +33 (0)4 73 40 77

17; Tel: +33 (0)4 73 40 54 27; E-mail: [email protected] dSchool of Science, University of Greenwich, Central Avenue, Chatham Maritime, Kent, ME4 4TB,

United Kingdom e Functional materials Group,

School of Physical Sciences, University of Kent, Canterbury, CN2 7NZ,

United Kingdom fDiamond Light Source Ltd., Diamond House, Harwell Science and Innovation Campus, Didcot, Oxfordshire, OX11 0DE, United Kingdom

Contents

CD studies ............................................................................................................................................... 4

Fig. S1 Molar ellipticity spectra of dimers in MeCN by ECD. All spectra were recorded at 20 °C at

known concentrations in the range 650 – 700 μM. ............................................................................. 4

Fig. S2 ECD spectra of dimers in MeCN processed by the number of chromophores. MCE is mean

chromophore ellipticity. All spectra were recorded at 20 °C at known concentrations in the range

650 – 700 μM. ..................................................................................................................................... 4

Table S1. Molar extinction coefficient (ε) of chromophores from literature.1 .................................... 5

Table S2 Processing strategy used to obtain MCE spectra. [] is molar ellipticity and (2n-1) is the

number of peptoid linkages within the backbone. ............................................................................... 5

Table S3 Position of positive and negative maxima for α,β-peptoid dimers in MeCN. All spectra

were recorded at 20 °C at known concentrations in the range 650 – 700 μM. .................................... 5

Fig. S3 MeCN/TFE solvent titration of 7 by ECD. All spectra were recorded at 20 °C at 699 μM or

700 μM. ............................................................................................................................................... 6

Fig. S4 ECD spectra of compounds (a) 7, (b) 1, (c) 10, (d) 4 and (e) 13. All spectra were recorded

at 20 °C at known concentrations in the range 650 - 750 μM. ............................................................ 7

Table S4 H-bonding ability of functional groups at the N- and C-termini.2-7

..................................... 7

Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2011

mailto:[email protected]

mailto:[email protected]

2

Fig. S5 Concentration studies of compounds (a) 4 and (b) 1 in MeCN by ECD. All spectra were

recorded at 20 °C at the concentrations stated. .................................................................................... 7

Fig. S6 Molar ellipticity spectra of (a) tetramers and (b) hexamers by ECD in MeCN. All spectra

were recorded at 20 °C at known concentrations in the range 499 – 500 μM for tetramers and 249 -

300 μM for hexamers. ......................................................................................................................... 8

Fig. S7 ECD spectra of hexamers in (a) MeCN, (b) TFE, (c) HFIP and (d) MeOH. All spectra were

recorded at 20 °C at known concentrations in the range 326 – 430 μM. ............................................ 8

Fig. S8 ECD spectra of hexamers of compounds (a) 9, (b) 3, (c) 12, (d) 6 and (e) 15 in different

solvents. All spectra were recorded at 20 °C at known concentrations in the range 326 – 430 μM. .. 9

Fig. S9 ECD spectra of dimers of a series in MeCN. (a) Molar ellipticity spectra and (b) MRE

spectra. All spectra were recorded at 20 °C at known concentrations in the range 299 - 700 μM. .... 9

Fig. S10 ECD spectra of dimers of b series in MeCN. (a) Molar ellipticity spectra and (b) MRE

spectra. All spectra were recorded at 20 °C at known concentrations in the range 299 – 700 μM. . 10

Fig. S11 ECD spectra of dimers of d series in MeCN. (a) Molar ellipticity spectra and (b) MRE

spectra. All spectra were recorded at 20 °C at known concentrations in the range 200 - 700 μM. .. 10

Fig. S12 ECD spectra of dimers of e series in MeCN. (a) Molar ellipticity spectra and (b) MRE

spectra. All spectra were recorded at 20 °C at known concentrations in the range 299 – 700 μM. . 10

Table S5 Actual concentrations used for CD analyses. All data have been recorded on a Chirascan

CD instrument (unless stated otherwise) by using a 0.01 cm path length cell. ................................. 11

IR studies and molecular modelling ...................................................................................................... 12

Fig. S13 Molecular modelling (PM6) for α,β-peptoid dimers 1, 4 and 13. ....................................... 12

Table S6. Assignment of IR bands for α,β-peptoid dimers 1, 4, 7 and 10 in CHCl3. ........................ 13

Fig. S14 N-H bonding spectral region and for α,β-peptoid 1 in CHCl3. All spectra were recorded at

room temperature at known concentrations in the range 1.43 – 23 mM but data are only shown for

the concentration range 5.75 – 23.0 mM. .......................................................................................... 14

Fig. S15 C=O bonding spectral region and for α,β-peptoid 1 in CHCl3. All spectra were recorded at

room temperature at known concentrations in the range 1.43 – 23 mM. .......................................... 14


room temperature at known concentrations in the range 1.43 – 23 mM but data are only shown for

the concentration range 5.75 – 23.0 mM. .......................................................................................... 14


room temperature at known concentrations in the range 1.43 – 23 mM. .......................................... 15

Fig. S18. N-H bonding spectral region and for α,β-peptoid hexamers 3, 6, 9, 12 and 15 in CHCl3.

All spectra were recorded at room temperature at known concentrations in the range ..................... 16

2 – 6 mM. .......................................................................................................................................... 16


3

Table S7. Actual concentration used for IR of α,β-peptoid dimers and hexamers in CHCl3. All

spectra have been recorded by using a KBr cell of 0.1 cm pathlength. ............................................. 16

Chemical structure of compounds 1a, 2a, 4a, 5a. ................................................................................. 17

Fig. S19 Chemical structure of intermediates 1a, 2a, 4a and 5a. ...................................................... 17

NMR studies .......................................................................................................................................... 17

Table S8. Cis/trans ratio for α,β-peptoid dimers in CDCl3 and CD3CN by NMR. ........................... 17

Table S9. Kcis/trans for α,β-peptoid 1, 2 and 3 in CD3CN calculated by 1H NMR.. ............................. 18

1H (400 MHz) and

13C (100.9 MHz) NMR spectra of compounds 1-20, 1a, 2a, 4a and 5a. ........ 19

Analytical HPLC analysis of peptoids .............................................................................................. 51

References ......................................................................................................................................... 55


4

CD studies

180 200 220 240 260-150

-100

-50

0

50

100

150

[] x 1

0-3

(deg.c

m2/d

mol)

wavelength (nm)

1

4

7

10

13

Fig. S1 Molar ellipticity spectra of dimers in MeCN by ECD. All spectra were recorded at 20 °C at

known concentrations in the range 650 – 700 μM.

Fig. S2 ECD spectra of dimers in MeCN processed by the number of chromophores. MCE is mean

chromophore ellipticity. All spectra were recorded at 20 °C at known concentrations in the range 650

– 700 μM.

Mean chromophore ellipticity (MCE) spectra were obtained by dividing the molar ellipticity spectra

by the number of chromophores that should contribute to the far UV region i.e. not only the tertiary

amide in the backbone. Therefore, this took into account the tertiary amide in the backbone, the

carbamate in the protecting group (Boc) and the free amine when the N-terminus was unprotected.

This was based on literature values identified for the molar extinction coefficient (ε) (reference S1)

(Table S1). The ester, the acid and the terminal amide were not considered due to their contribution to

the far UV region being negligible. When doing this calculation it was found that by considering these

three chromophores, all the compounds would have been divided by the same number. For this reason

it was decided to repeat the calculation without considering the amine chromophore which was the

least intense of the three (Table S2). However, it is of note that the values of ε reported for the isolated

chromophores are an approximation obtained from the value of the simplest molecule containing the

functional group considered. In addition to this MCE data were not corrected for the relative

contribution of the isolated chromophore i.e. all the contributing chromophores were assumed to have

the same contribution (same ε value). Due to these approximations, processing by MCE is arbitrary.


5

Despite this, the processing is still adequate to show that additional chromophores would change the

spectral intensity but not the spectral shape. This confirms that the difference observed in the MRE

spectra (Figure 2) was due to the effect of protecting groups on the conformational preference and not

simply to the presence of the additional chromophores.

Isolated

chromophore Reference compound

Typical

wavelength ε (liter mol

-1 cm

-1)

Tertiary amide CH3CON(CH3)2 218 1000

CH3CON(CH3)(Ph) 224 7870

Primary amide

CH3CONH2 205 162

HCONH2 205 158

Ester CH3COOEt 209 72

Carbamate NO2NHCOOC2H5 215 7943

Carboxyl CH3COOH 208 32

Secondary amine (CH3)2NH 191 3236

Table S1. Molar extinction coefficient (ε) of chromophores from literature.1

Series R

1 R

2 Processing

a H OtBu []/[(2n-1) + 0]

b H NH2 []/[(2n-1) + 0]

c Boc OtBu []/[(2n-1) + 1]

d Boc NH2 []/[(2n-1) + 1]

e TFA·H OH []/[(2n-1) + 0]

Table S2 Processing strategy used to obtain MCE spectra. [] is molar ellipticity and (2n-1) is the

number of peptoid linkages within the backbone.

Dimer λmax peak I λmax peak II λmax peak III

1 184 (+ve) 194 (-ve) 219 (-ve)

4 184 (+ve) 194 (-ve) 219 (-ve)

7 180 (+ve) 200 (-ve) 217 (-ve)

10 180 (+ve) 200 (-ve) 217 (-ve)

13 184 (+ve) 194 (-ve) 216 (-ve)

Table S3 Position of positive and negative maxima for α,β-peptoid dimers in MeCN. All spectra were

recorded at 20 °C at known concentrations in the range 650 – 700 μM.


6

180 190 200 210 220 230 240 250 260-50

-25

0

25

50

MR

E x

10

-3 (

deg.c

m2/d

mol)

wavelength (nm)

MeCN

MeCN:TFE 3:1

MeCN:TFE 1:1

MeCN:TFE 1:3

TFE

185 190 195-30

-20

-10

0

10

20

30

Fig. S3 MeCN/TFE solvent titration of 7 by ECD. All spectra were recorded at 20 °C at 699 μM

or 700 μM.

180 200 220 240 260-150

-100

-50

0

50

100

150

(a)

[]

x 1

0-3

(de

g.c

m2/d

mo

l)

wavelength (nm)

MeCN

TFE

HFIP

MeOH

180 200 220 240 260-150

-100

-50

0

50

100

150

(b)[

] x 1

0-3 (

de

g.c

m2/d

mo

l)

wavelength (nm)

MeCN

TFE

HFIP

MeOH

180 200 220 240 260-150

-100

-50

0

50

100

150

(c)

[]

x 1

0-3

(de

g.c

m2/d

mo

l)

wavelength (nm)

MeCN

TFE

HFIP

MeOH

180 200 220 240 260-150

-100

-50

0

50

100

150

(d)

[]

x 1

0-3 (

de

g.c

m2/d

mo

l)

wavelength (nm)

MeCN

TFE

HFIP

MeOH


7

180 200 220 240 260-150

-100

-50

0

50

100

150

(e)

[]

x 1

0-3 (

de

g.c

m2/d

mo

l)

wavelength (nm)

MeCN

TFE

HFIP

MeOH

Fig. S4 ECD spectra of compounds (a) 7, (b) 1, (c) 10, (d) 4 and (e) 13. All spectra were recorded

at 20 °C at known concentrations in the range 650 - 750 μM.

Functional

group α-value β-value

3° Amide 0.00 0.69 - 0.78

Carbamate 0.00 0.6 - 0.65

2° Amine 0.08 0.6 - 0.7

Ester 0.00 0.47

1° Amide 0.54 0.66-0.69

Acid 0.55 0.45

Table S4 H-bonding ability of functional groups at the N- and C-termini.

2-7

190 200 210 220 230 240 250 260-50

-40

-30

-20

-10

0

10

(a)

wavelength (nm)

MR

E x

10

-3 (

deg.c

m2/d

mol)

1 mM

500 M

100 M

50 M

10 M

5 M

190 200 210 220 230 240 250 260-50

-40

-30

-20

-10

0

10

(b)

wavelength (nm)

MR

E x

10

-3 (

de

g.c

m2/d

mo

l)

1 mM

500 M

100 M

50 M

10 M

5 M

Fig. S5 Concentration studies of compounds (a) 4 and (b) 1 in MeCN by ECD. All spectra were recorded at 20 °C at the concentrations stated.


8

180 200 220 240 260-150

-100

-50

0

50

100

150

200

(a)

wavelength (nm)

[]

x 1

0-3

(d

eg

.cm

2/d

mo

l)

2

5

8

11

14

180 200 220 240 260

-300

-200

-100

0

100

200

300

(b)

[] x

10

-3 (d

eg.c

m2/d

mol

)

wavelength (nm)

3

6

9

12

15

Fig. S6 Molar ellipticity spectra of (a) tetramers and (b) hexamers by ECD in MeCN. All spectra were

recorded at 20 °C at known concentrations in the range 499 – 500 μM for tetramers and 249 - 300 μM

for hexamers.

180 200 220 240 260-80

-60

-40

-20

0

20

40

60

80

(a)

wavelength (nm)

MR

E x

10

-3 (

deg.c

m2/d

mol)

3

6

9

12

15

180 200 220 240 260

-80

-60

-40

-20

0

20

40

60

80

(b)

MR

E x

10

-3 (d

eg.c

m2/d

mol)

wavelength (nm)

3

6

9

12

15

180 200 220 240 260-80

-60

-40

-20

0

20

40

60

80

(c)

MR

E x

10

-3 (d

eg.c

m2/d

mol)

wavelength (nm)

3

6

9

12

15

180 200 220 240 260-80

-60

-40

-20

0

20

40

60

80

(d)

MR

E x

10

-3 (d

eg.c

m2/d

mol)

wavelength (nm)

3

6

9

12

15

Fig. S7 ECD spectra of hexamers in (a) MeCN, (b) TFE, (c) HFIP and (d) MeOH. All spectra were recorded at 20 °C at known concentrations in the range 326 – 430 μM.


9

180 200 220 240 260-400

-200

0

200

400

(a)[

] x 1

0-3

(deg.c

m2/d

mol)

wavelength (nm)

MeCN

TFE

HFIP

MeOH

180 200 220 240 260-400

-200

0

200

400

(b)

[] x 1

0-3

(deg.c

m2/d

mol)

wavelength (nm)

MeCN

TFE

HFIP

MeCN

180 200 220 240 260-400

-200

0

200

400

(c)

[] x 1

0-3

(deg.c

m2/d

mol)

wavelength (nm)

MeCN

TFE

HFIP

MeOH

180 200 220 240 260-400

-200

0

200

400

(d)

[]

x 1

0-3

(de

g.c

m2/d

mo

l)

wavelength (nm)

MeCN

TFE

HFIP

MeOH

180 200 220 240 260-400

-200

0

200

400

(e)

[] x 1

0-3

(deg.c

m2/d

mol)

wavelength (nm)

MeCN

TFE

HFIP

MeOH

Fig. S8 ECD spectra of hexamers of compounds (a) 9, (b) 3, (c) 12, (d) 6 and (e) 15 in different

solvents. All spectra were recorded at 20 °C at known concentrations in the range 326 – 430 μM.

180 200 220 240 260-300

-200

-100

0

100

200

300

(a)

[]

x 1

0-3 (

de

g.c

m2/d

mo

l)

wavelength (nm)

1

2

3

180 200 220 240 260-80

-60

-40

-20

0

20

40

60

80

(b)

MR

E x

10

-3 (

de

g.c

m2/d

mo

l)

wavelength (nm)

1

2

3

Fig. S9 ECD spectra of dimers of a series in MeCN. (a) Molar ellipticity spectra and (b) MRE spectra.

All spectra were recorded at 20 °C at known concentrations in the range 299 - 700 μM.


10

180 200 220 240 260-300

-200

-100

0

100

200

300(a)

[] x 1

0-3 (

deg.c

m2/d

mol)

wavelength (nm)

4

5

6

180 200 220 240 260-80

-60

-40

-20

0

20

40

60

80

(b)

MR

E x

10

-3 (

de

g.c

m2/d

mo

l)

wavelength (nm)

4

5

6

Fig. S10 ECD spectra of dimers of b series in MeCN. (a) Molar ellipticity spectra and (b) MRE

spectra. All spectra were recorded at 20 °C at known concentrations in the range 299 – 700 μM.

180 200 220 240 260-400

-300

-200

-100

0

100

200

300

400

(a)

[]

x 1

0-3 (

de

g.c

m2/d

mo

l)

wavelength (nm)

10

11

12

19

20

180 200 220 240 260

-80

-60

-40

-20

0

20

40

60

80(b)

MR

E x

10

-3 (

deg.c

m2/d

mol)

wavelength (nm)

10

11

12

19

20

Fig. S11 ECD spectra of dimers of d series in MeCN. (a) Molar ellipticity spectra and (b) MRE

spectra. All spectra were recorded at 20 °C at known concentrations in the range 200 - 700 μM.

180 200 220 240 260-300

-200

-100

0

100

200

300

(a)

[]

x 1

0-3 (

de

g.c

m2/d

mo

l)

wavelength (nm)

13

14

15

180 200 220 240 260-80

-60

-40

-20

0

20

40

60

80

(b)

MR

E x

10

-3 (

de

g.c

m2/d

mo

l)

wavelength (nm)

13

14

15

Fig. S12 ECD spectra of dimers of e series in MeCN. (a) Molar ellipticity spectra and (b) MRE

spectra. All spectra were recorded at 20 °C at known concentrations in the range 299 – 700 μM.


11

Series peptoid MeCN TFE HFIP MeOH

a

1 700 μM 779 μM 718 μM 705 μM

2 500 μM - - -

3 299 μM

441 μM* 402 μM* 384 μM* 381 μM*

b

4 700 μM 699 μM 750 μM 743 μM

5 500 μM - - -

6 299 μM

365 μM* 399 μM* 371 μM* 366 μM*

c

7

652 μM

2.3 mM* 700 μM

700 μM 734 μM MeCN/TFE 1:0 699 μM

MeCN/TFE 3:1 699 μM




8 499 μM

666 μM* - - -

9

249 μM

385 μM*

385 μM*

365 μM* 326 μM* 392 μM*

17 188 μM* - - -

18 150 μM* - - -

d

10

700 μM 710 μM 727 μM 710 μM






- -

11 500 μM - - -

12 300 μM

430 μM* 415 μM* 405 μM* 429 μM*

19 200 μM - - -

20 200 μM - - -

e

13 700 μM 703 μM 700 μM 724 μM

14 499 μM - - -

15

299 μM

352 μM* 370 μM* 399 μM* 382 μM*

* Data recorded by SRCD

Table S5 Actual concentrations used for CD analyses. All data have been recorded on a Chirascan CD

instrument (unless stated otherwise) by using a 0.01 cm path length cell.


12

IR studies and molecular modelling

Fig. S13 Molecular modelling (PM6) for α,β-peptoid dimers 1, 4 and 13.


13

Compound λ (cm-1

) Assignment

1

3420

3314

1714

1636

NH (amine) unassociated

NH (amine) H-bonded

C=O (ester)C=O (3º amide) H-bonded

4

3516

~3485

3402

3321

1681

1636

1600

1592

N-H (asym, 1º amide) unassociated

N-H (sym, 1º amide) H-bonded


NH (amine) H-bonded and

N-H (asym, 1ºamide) H-bonded

C=O (carbamate)

C=O (3º amide) H-bonded

δNH2 H-bonded H-bonded

δ NH2 H-bonded unassociated

7

1721

1688

1660

C=O (ester)

C=O (carbamate)C=O (3º amide) unassociated

10

3526

3485

3409

3344

1687

1656

1601(sh)

1592


N-H (sym, 1ºamide) H-bonded


N-H (asym, 1ºamide) H-bonded

C=O (carbamate)

C=O (3º amide)

δ NH2 H-bonded H-bonded

δ NH2 H-bonded unassociated

Table S6. Assignment of IR bands for α,β-peptoid dimers 1, 4, 7 and 10 in CHCl3.


14


room temperature at known concentrations in the range 1.43 – 23 mM but data are only shown for the

concentration range 5.75 – 23.0 mM.


room temperature at known concentrations in the range 1.43 – 23 mM.


room temperature at known concentrations in the range 1.55 – 25.0 mM.


15


room temperature at known concentrations in the range 1.55 – 25.0 mM.


16

Fig. S18. N-H bonding spectral region and for α,β-peptoid hexamers 3, 6, 9, 12 and 15 in CHCl3. All

spectra were recorded at room temperature at known concentrations in the range

2 – 6 mM.

Series Peptoid Concentration

(mM)

a 1 23.7 3 5.6

b 4 25.1 6 5.8

c 7 10.0 9 5.6

d 10 21.3 12 5.1

e 13 21.0 15 5.1

Table S7. Actual concentration used for IR of α,β-peptoid dimers and hexamers in CHCl3. All spectra

have been recorded by using a KBr cell of 0.1 cm pathlength.


17

Chemical structure of compounds 1a, 2a, 4a, 5a.

Fig. S19 Chemical structure of intermediates 1a, 2a, 4a and 5a.

NMR studies

Structure Peptoid cis/trans ratio in CDCl3 cis/trans ratio in

CD3CN

1 0.61 (38:62) (1H) 0.64 (39:61) (

1H)

4 0.43 (30:70) (

1H)

0.39 (28:72) (HSQC) 0.89 (47:53) (

1H)

7 inconclusive/overlapping

signals

inconclusive/overlapping

signals

10 inconclusive/overlapping

signals

inconclusive/overlapping

signals

13

0.69 (41:59) (

1H) 0.85 (46:54) (

1H)

Table S8. Cis/trans ratio for α,β-peptoid dimers in CDCl3 and CD3CN at 298 K by NMR.

OtBuN

O

Ph

HN

OPh

NH2N

O

Ph

HN

OPh

OtBuN

O

Ph

BocN

OPh

OHN

O

Ph

TFA.HN

OPh

NH2N

O

Ph

BocN

OPh


18

Structure Peptoid Kcis/trans (cis/trans ratio)

298K 318K 338K

1 0.65 (39:61) 0.63 (38:62) -

2 0.92 (48:52) 0.94 (49:51) 0.93 (48:52)

3 1.08 (52:48) 1.08 (52:48) 1.10 (53:47)

Table S9. Kcis/trans for α,β-peptoid 1, 2 and 3 in CD3CN calculated by 1H NMR.

OtBuN

O

Ph

HN

OPh

OtBuN

O

NH

O

Ph

Ph

2

OtBuN

O

NH

O

Ph

Ph

3


19

1H (400 MHz) and

13C (100.9 MHz) NMR spectra of compounds 1-20, 1a, 2a, 4a and 5a.


20

1H and

13C NMR spectra of compound 1 (CDCl3)

ppm (t1)0.01.02.03.04.05.06.07.0

10

.49

0.4

0

0.6

6

1.0

0

4.0

0

3.2

8

2.9

0

12

.11

ppm (t1)050100150

17

1.1

40

17

0.9

81

17

0.8

78

16

9.8

10

14

4.8

80

14

4.8

33

14

0.2

12

13

9.6

72

12

8.6

16

12

8.4

14

12

7.6

07

12

7.4

34

12

6.9

74

12

6.7

24

12

6.5

24

80

.89

5

80

.36

5

58

.26

4

58

.04

8

53

.92

3

51

.48

3

48

.81

7

48

.62

6

38

.87

3

38

.27

4

36

.14

2

34

.31

0

27

.95

5

27

.85

2

24

.61

0

24

.57

5

17

.91

6

16

.56

7

OtBuN

O

Ph

HN

OPh


21

1H NMR spectrum of compound 1 (CD3CN)

ppm (t1)050100150

17

4.6

10

17

4.4

75

17

3.6

97

17

3.2

68

17

2.5

13

17

2.3

61

17

1.7

01

16

8.9

86

16

8.9

25

16

8.5

13

16

8.0

57

16

7.9

15

15

5.7

50

15

5.5

99

14

1.9

31

14

1.3

83

14

1.0

54

14

0.5

07

14

0.1

00

13

9.7

25

13

9.5

58

13

9.3

26

13

9.2

26

13

8.9

98

13

8.8

42

12

8.9

36

12

8.7

21

12

8.6

53

12

8.4

29

12

8.3

77

12

8.2

51

12

7.6

72

12

7.5

62

12

7.4

23

12

7.2

50

12

7.0

82

12

6.9

62

12

6.8

15

12

6.7

29

12

6.5

45

81

.21

1

80

.05

4

55

.27

5

55

.17

5

55

.04

8

54

.84

0

54

.78

6

54

.70

9

54

.56

5

54

.37

2

54

.07

9

53

.21

8

53

.13

9

52

.47

7

51

.68

0

51

.54

5

51

.44

4

51

.28

2

50

.99

9

50

.78

6

45

.64

8

45

.45

3

45

.34

3

45

.15

8

44

.95

2

44

.56

8

44

.24

1

43

.93

9

43

.74

9

40

.80

4

39

.98

2

39

.70

3

38

.95

7

38

.79

2

38

.35

8

34

.83

5

34

.61

9

34

.36

3

33

.79

8

33

.50

4

33

.18

4

28

.32

0

18

.65

7

18

.52

9

18

.34

7

18

.26

7

18

.02

5

17

.93

4

17

.72

1

17

.62

5

17

.38

4

17

.22

4

17

.09

1

16

.85

0

16

.62

1

16

.44

2

16

.36

7

16

.17

3

16

.02

4

OtBuN

O

Ph

HN

OPh


22

1H and

13C NMR spectra of compound 1a (CDCl3)

ppm (t1)0.01.02.03.04.05.06.07.0

15

.00

17

.30

1.8

6

2.9

6

3.8

7

2.5

6

0.4

8

0.4

0

0.2

1

0.1

6

0.4

6

0.2

6

0.2

0

ppm (t1)050100150

17

3.3

05

17

3.1

62

17

2.4

49

17

1.0

73

17

0.7

25

17

0.0

51

16

9.7

05

16

8.1

73

16

7.9

31

16

7.7

22

16

7.3

50

14

5.6

28

14

0.8

17

14

0.7

12

14

0.6

60

14

0.4

36

14

0.0

63

13

9.4

21

13

9.4

03

12

8.8

20

12

8.6

34

12

8.5

30

12

8.3

47

12

8.2

63

12

7.7

82

12

7.7

13

12

7.5

85

12

7.5

01

12

7.3

50

12

6.8

24

12

6.6

14

12

6.2

40

81

.18

1

80

.82

9

80

.54

7

80

.20

4

58

.31

2

58

.18

8

55

.33

8

55

.21

7

54

.61

2

54

.21

0

51

.87

3

51

.49

4

50

.98

4

45

.07

5

44

.97

3

44

.07

8

43

.51

4

39

.55

9

39

.22

9

38

.59

9

38

.27

9

36

.23

7

35

.75

8

34

.15

9

33

.63

5

27

.93

7

27

.88

2

24

.38

0

16

.40

5

16

.31

7

16

.07

5

15

.99

5

OtBuN

O

Ph

N

OPh

O

HN

Ph


23

1H and


ppm (t1)0.01.02.03.04.05.06.07.0

1.2

2

21

.06

21

.00

5.3

3

9.2

2

0.2

9

1.4

3

ppm (t1)050100150

17

2.2

62

17

2.1

06

17

1.3

14

17

1.1

82

17

1.0

72

17

1.0

06

17

0.9

13

17

0.7

79

17

0.6

10

17

0.2

92

17

0.2

47

17

0.0

05

16

9.9

53

16

9.6

65

16

8.3

05

16

8.0

37

16

7.8

84

16

7.7

54

16

7.6

17

16

7.4

01

16

7.0

04

16

6.9

08

14

4.7

94

14

0.6

27

14

0.5

01

14

0.3

11

14

0.1

78

13

9.9

51

13

9.9

13

13

9.7

32

13

9.3

68

13

9.2

35

13

9.0

31

12

8.9

39

12

8.6

23

12

8.5

59

12

8.3

53

12

7.9

94

12

7.7

65

12

7.5

43

12

7.4

30

12

7.2

93

12

6.9

29

12

6.8

50

12

6.6

62

12

6.5

14

12

6.3

68

12

6.0

45

12

5.9

40

80

.42

5

80

.15

8

58

.41

1

58

.36

0

57

.98

2

57

.83

1

57

.76

5

55

.12

6

55

.02

2

54

.51

6

54

.36

6

54

.19

5

54

.11

0

54

.03

3

52

.01

5

51

.82

5

51

.39

4

51

.32

1

51

.23

9

50

.74

9

49

.06

1

48

.88

1

48

.68

3

48

.52

7

45

.10

9

44

.92

4

44

.60

1

44

.04

6

43

.91

7

40

.26

1

40

.15

2

39

.91

9

39

.84

0

39

.55

3

39

.18

4

39

.07

9

38

.82

4

38

.50

4

38

.43

3

38

.32

9

36

.19

6

36

.11

4

35

.64

3

35

.55

1

34

.11

5

33

.96

2

33

.71

5

33

.57

2

33

.38

2

33

.14

8

32

.65

8

32

.54

3

27

.90

4

27

.86

0

24

.60

8

24

.56

0

24

.41

8

18

.56

2

18

.49

1

18

.38

5

18

.33

2

18

.26

3

18

.17

8

17

.83

1

16

.49

6

16

.37

7

16

.20

5

16

.15

4

15

.98

3

15

.82

3

OtBuN

O

NH

O

Ph

Ph

2


24



25

1H and


ppm (t1)0.01.02.03.04.05.06.07.0

25

.98

1.7

6

24

.00

2.0

1

10

.08

8.1

5

ppm (t1)050100150

17

3.1

97

17

3.0

75

17

2.3

61

17

1.6

80

17

1.3

68

17

1.2

40

17

1.1

40

17

0.9

17

17

0.7

33

17

0.0

79

17

0.0

01

16

9.6

31

16

9.5

78

16

8.5

97

16

8.5

31

16

8.4

10

16

8.1

92

16

8.1

17

16

7.8

93

16

7.8

26

16

7.7

45

16

7.5

55

16

7.3

99

16

7.2

68

16

7.0

91

16

7.0

26

14

4.9

48

14

4.8

72

14

0.7

83

14

0.6

16

14

0.5

45

14

0.4

10

14

0.3

05

14

0.1

96

14

0.0

21

13

9.8

03

13

9.4

33

13

9.2

13

13

8.9

80

12

8.8

29

12

8.7

90

12

8.6

70

12

8.5

46

12

8.3

63

12

8.3

09

12

7.9

20

12

7.8

16

12

7.6

21

12

7.5

55

12

7.3

75

12

7.2

81

12

7.0

23

12

6.7

95

12

6.6

69

12

6.3

65

12

6.2

31

12

6.1

62

12

6.1

03

80

.39

3

80

.35

1

58

.40

3

58

.31

0

58

.20

2

55

.58

0

55

.45

4

55

.39

1

55

.22

6

55

.18

9

55

.13

1

55

.01

0

54

.70

3

54

.57

8

54

.48

7

54

.43

1

54

.34

3

54

.17

7

51

.92

6

51

.76

8

51

.67

6

51

.50

8

51

.38

8

51

.24

2

50

.98

2

50

.92

5

50

.84

3

50

.66

4

45

.05

8

44

.98

3

44

.92

6

44

.79

9

44

.59

5

44

.49

2

44

.38

8

44

.26

3

44

.19

1

44

.04

5

43

.91

1

43

.42

0

41

.02

0

40

.71

3

40

.48

5

40

.44

1

40

.25

4

40

.16

5

39

.84

0

39

.56

0

39

.42

3

39

.36

6

39

.28

4

39

.13

4

38

.80

1

38

.46

4

38

.27

9

36

.20

0

36

.13

9

35

.61

6

34

.15

0

34

.03

8

33

.92

2

33

.84

4

33

.62

6

33

.47

1

33

.34

7

33

.28

0

33

.18

4

32

.88

4

32

.37

8

32

.23

1

27

.93

2

27

.87

3

24

.23

8

24

.10

3

23

.94

9

23

.87

7

23

.73

7

18

.74

3

18

.55

7

18

.43

3

18

.26

0

18

.10

7

17

.85

4

17

.72

1

16

.53

6

16

.39

7

16

.30

5

16

.21

6

16

.14

91

6.0

18

15

.78

8

OtBuN

O

N

O

Ph

Ph

2

HN

Ph

O


26

1H and


ppm (t1)0.01.02.03.04.05.06.07.0

31

.31

27

.00

2.1

2

2.6

4

12

.84

6.8

5

ppm (t1)050100150

17

2.2

41

17

2.1

84

17

2.0

46

17

1.4

78

17

1.2

60

17

1.1

15

17

1.0

03

17

0.9

07

17

0.7

82

17

0.6

14

17

0.2

24

17

0.1

37

16

9.9

55

16

8.5

39

16

8.4

18

16

8.1

07

16

8.0

66

16

7.8

48

16

7.8

03

16

7.1

93

16

7.0

79

14

4.8

31

14

0.9

99

14

0.9

25

14

0.7

45

14

0.6

12

14

0.4

87

14

0.4

13

14

0.2

51

14

0.1

55

14

0.0

54

13

9.9

42

13

9.8

06

13

9.7

38

13

9.4

13

13

9.3

50

13

9.2

07

13

9.1

30

13

9.0

52

12

8.5

72

12

8.3

27

12

7.5

03

12

7.3

45

12

6.8

93

12

6.7

66

12

6.6

31

12

6.4

89

12

6.3

70

12

6.2

92

80

.39

4

80

.28

1

58

.38

1

57

.89

4

57

.78

5

55

.37

8

55

.25

2

55

.16

1

55

.01

0

54

.95

0

54

.74

0

54

.60

3

54

.47

4

54

.41

8

54

.35

2

54

.25

3

54

.04

2

51

.79

6

51

.73

3

51

.63

8

51

.59

1

51

.44

9

51

.37

9

51

.21

7

51

.11

7

50

.90

3

50

.78

8

50

.64

8

50

.60

2

49

.04

3

48

.91

6

48

.63

0

48

.42

1

45

.14

0

45

.02

0

44

.90

7

44

.78

7

44

.72

0

44

.58

7

44

.50

8

44

.33

7

44

.26

7

44

.18

0

44

.12

5

43

.97

6

43

.86

8

40

.63

1

40

.22

7

40

.12

7

39

.83

4

39

.69

2

39

.52

4

39

.37

3

39

.25

1

39

.17

9

39

.09

4

38

.84

8

38

.75

8

38

.56

5

38

.41

5

38

.19

9

36

.15

0

36

.11

2

35

.55

3

34

.10

8

33

.91

3

33

.85

9

33

.79

1

33

.64

6

33

.51

6

33

.39

9

33

.29

8

33

.24

9

32

.53

9

32

.36

3

32

.23

5

27

.89

2

27

.83

2

24

.55

7

24

.41

7

24

.23

9

24

.04

0

18

.86

0

18

.66

2

18

.45

5

18

.37

8

18

.20

3

18

.14

7

18

.09

6

17

.97

6

17

.86

4

17

.69

8

17

.57

51

6.5

16

16

.36

81

6.2

64

16

.14

81

5.9

51

15

.82

3

OtBuN

O

NH

O

Ph

Ph

3


27



28

1H and


ppm (t1)0.01.02.03.04.05.06.07.0

10

.82

0.7

0

0.2

6

0.9

7

0.3

0

0.6

4

1.0

0

4.0

4

1.4

2

3.0

3

2.9

8

0.7

1

0.7

3

0.2

8

0.3

3

ppm (t1)050100150

17

3.7

18

17

2.1

25

17

1.2

23

17

1.0

10

14

4.6

12

14

0.3

45

13

9.4

14

12

8.7

08

12

8.4

74

12

7.7

85

12

7.5

36

12

7.0

97

12

6.8

76

12

6.6

99

12

6.5

80

58

.31

8

57

.95

2

54

.13

5

51

.41

7

48

.86

1

48

.45

3

39

.75

6

38

.60

8

35

.93

5

35

.61

5

24

.49

8

24

.36

8

17

.85

3

16

.42

8

NH2N

O

Ph

HN

OPh


29


ppm (t1)050100150

17

4.6

10

17

4.4

75

17

3.6

97

17

3.2

68

17

2.5

13

17

2.3

61

17

1.7

01

16

8.9

86

16

8.9

25

16

8.5

13

16

8.0

57

16

7.9

15

15

5.7

50

15

5.5

99

14

1.9

31

14

1.3

83

14

1.0

54

14

0.5

07

14

0.1

00

13

9.7

25

13

9.5

58

13

9.3

26

13

9.2

26

13

8.9

98

13

8.8

42

12

8.9

36

12

8.7

21

12

8.6

53

12

8.4

29

12

8.3

77

12

8.2

51

12

7.6

72

12

7.5

62

12

7.4

23

12

7.2

50

12

7.0

82

12

6.9

62

12

6.8

15

12

6.7

29

12

6.5

45

81

.21

1

80

.05

4

55

.27

5

55

.17

5

55

.04

8

54

.84

0

54

.78

6

54

.70

9

54

.56

5

54

.37

2

54

.07

9

53

.21

8

53

.13

9

52

.47

7

51

.68

0

51

.54

5

51

.44

4

51

.28

2

50

.99

9

50

.78

6

45

.64

8

45

.45

3

45

.34

3

45

.15

8

44

.95

2

44

.56

8

44

.24

1

43

.93

9

43

.74

9

40

.80

4

39

.98

2

39

.70

3

38

.95

7

38

.79

2

38

.35

8

34

.83

5

34

.61

9

34

.36

3

33

.79

8

33

.50

4

33

.18

4

28

.32

0

18

.65

7

18

.52

9

18

.34

7

18

.26

7

18

.02

5

17

.93

4

17

.72

1

17

.62

5

17

.38

4

17

.22

4

17

.09

1

16

.85

0

16

.62

1

16

.44

2

16

.36

7

16

.17

3

16

.02

4

NH2N

O

Ph

HN

OPh


30

1H and


ppm (t1)0.01.02.03.04.05.06.07.0

9.0

0

15

.55

0.2

1

0.3

6

0.3

5

0.3

9

0.2

3

0.6

0

1.5

1

0.6

2

0.3

3

0.5

8

1.3

2

1.9

4

7.5

2

ppm (t1)050100150

17

3.8

64

17

3.3

35

17

3.1

61

17

2.9

95

17

2.6

24

17

2.5

17

16

8.3

68

16

8.1

95

16

7.8

56

14

5.5

64

14

5.4

58

14

4.9

62

14

4.8

82

14

0.8

56

14

0.7

60

14

0.4

26

14

0.3

02

14

0.1

67

14

0.0

81

13

9.1

70

13

9.1

22

12

8.8

67

12

8.6

66

12

8.5

64

12

8.3

85

12

8.3

20

12

7.9

52

12

7.8

39

12

7.7

69

12

7.6

44

12

7.5

29

12

7.4

48

12

7.3

83

12

6.8

95

12

6.8

33

12

6.7

61

12

6.6

00

12

6.3

36

58

.58

5

58

.39

9

58

.24

6

55

.52

9

55

.25

9

54

.83

5

54

.44

4

51

.88

5

51

.58

9

51

.22

9

51

.12

1

45

.13

1

44

.47

5

44

.17

1

43

.48

6

43

.42

5

40

.70

4

40

.24

6

38

.95

8

38

.62

8

35

.93

5

35

.70

3

35

.38

6

35

.24

4

33

.59

3

24

.32

8

23

.99

1

18

.52

7

18

.26

4

17

.70

8

16

.39

1

16

.25

0

16

.16

9

NH2N

O

Ph

N

OPh

O

HN

Ph


31

1H and


ppm (t1)0.01.02.03.04.05.06.07.0

12

.00

20

.96

0.4

4

0.1

5

0.0

7

1.2

2

1.0

2

0.2

7

1.1

3

0.2

3

0.8

3

8.0

1

5.1

3

ppm (t1)050100150

17

3.7

91

17

3.6

89

17

3.0

41

17

2.5

80

17

2.1

38

17

1.9

47

17

1.3

67

17

1.1

90

17

1.0

49

17

0.9

16

17

0.8

41

17

0.4

02

17

0.3

27

16

8.5

77

16

8.2

26

16

8.1

10

16

7.6

88

16

7.4

84

16

7.3

75

14

4.7

27

14

4.6

57

14

4.5

66

14

4.0

99

14

0.7

30

14

0.6

12

14

0.5

62

14

0.5

15

14

0.4

52

14

0.1

09

13

9.8

76

13

9.7

05

13

9.5

78

13

9.1

98

13

9.0

88

13

9.0

21

12

8.9

29

12

8.7

25

12

8.6

46

12

8.5

58

12

8.4

58

12

8.3

89

12

8.0

56

12

7.8

14

12

7.7

23

12

7.6

77

12

7.6

01

12

7.5

41

12

7.4

58

12

7.4

11

12

7.3

27

12

7.0

96

12

6.9

78

12

6.9

25

12

6.6

98

12

6.5

71

12

6.4

55

12

6.2

97

12

6.2

31

58

.42

4

58

.38

4

58

.21

4

58

.03

3

57

.84

4

57

.78

0

55

.32

8

55

.05

2

54

.80

3

54

.57

8

54

.36

4

54

.30

1

54

.05

3

52

.85

2

52

.01

1

51

.82

9

51

.53

8

51

.35

2

51

.08

8

50

.97

4

50

.85

3

49

.04

7

48

.94

3

48

.64

3

48

.29

9

47

.94

8

45

.33

5

45

.12

4

45

.04

4

44

.71

3

44

.40

8

44

.25

7

44

.12

6

43

.97

9

40

.45

3

40

.09

9

39

.79

3

39

.00

3

38

.88

4

38

.85

4

36

.09

9

35

.87

3

35

.68

8

35

.35

1

35

.22

9

34

.86

6

34

.20

1

34

.03

9

33

.91

5

33

.42

3

32

.45

9

24

.51

8

24

.43

1

24

.31

4

24

.28

9

23

.85

9

23

.46

1

18

.66

3

18

.51

3

18

.29

2

18

.23

9

18

.09

2

17

.87

8

17

.65

3

16

.85

7

16

.67

1

16

.48

6

16

.39

6

16

.21

2

16

.08

4

15

.95

1

NH2N

O

NH

O

Ph

Ph

2


32

1H and


ppm (t1)0.01.02.03.04.05.06.07.0

15

.00

26

.61

9.1

0

8.7

5

2.0

1

0.4

8

0.3

9

0.5

4

0.6

0

0.7

7

0.0

5

ppm (t1)050100150

17

4.3

94

17

4.1

27

17

3.8

06

17

3.3

82

17

3.2

21

17

3.1

46

17

2.8

70

17

2.6

35

17

2.4

85

17

2.3

95

17

2.2

71

17

2.1

48

17

1.8

75

17

1.6

88

17

1.3

90

17

1.3

08

17

0.8

05

16

8.7

75

16

8.6

71

16

8.1

75

16

7.9

73

16

7.9

11

16

7.7

89

16

7.5

06

16

7.4

72

16

7.3

09

14

5.3

26

14

5.1

94

14

4.9

42

14

1.0

34

14

0.7

79

14

0.6

72

14

0.4

51

14

0.2

84

14

0.1

55

14

0.1

24

14

0.0

75

13

9.8

43

13

9.6

16

13

9.3

96

13

9.0

87

13

9.0

08

13

8.9

24

12

8.9

26

12

8.7

87

12

8.6

46

12

8.5

91

12

8.4

81

12

8.4

47

12

8.3

46

12

8.2

56

12

8.1

08

12

7.9

80

12

7.7

90

12

7.6

60

12

7.4

79

12

7.3

54

12

7.2

82

12

7.1

53

12

7.0

59

12

6.8

68

12

6.7

54

12

6.6

73

12

6.5

84

12

6.5

48

12

6.5

14

12

6.4

36

12

6.3

67

12

6.1

82

12

6.0

88

58

.53

3

58

.50

0

58

.32

8

58

.19

6

58

.03

9

55

.82

3

55

.74

9

55

.67

6

55

.54

9

55

.41

2

55

.13

4

55

.05

1

54

.86

9

54

.70

6

54

.51

4

54

.40

5

54

.28

9

52

.37

6

52

.28

6

52

.13

6

51

.87

4

51

.69

3

51

.55

7

51

.37

6

51

.15

4

51

.00

7

50

.94

2

50

.86

5

45

.46

9

45

.29

0

45

.22

5

45

.17

6

45

.08

5

44

.88

4

44

.73

7

44

.57

3

44

.35

9

44

.19

4

44

.13

2

43

.99

6

43

.90

1

43

.52

4

43

.46

6

43

.40

5

43

.34

7

42

.91

1

42

.56

9

41

.77

9

41

.46

8

41

.35

6

41

.25

7

40

.79

1

40

.47

2

40

.28

8

40

.06

5

39

.30

0

39

.14

2

38

.98

4

38

.81

2

38

.61

8

36

.76

8

35

.80

5

35

.43

3

35

.31

6

34

.93

2

34

.30

9

34

.14

2

33

.92

7

33

.65

0

33

.49

5

33

.39

6

33

.07

9

32

.36

7

32

.17

9

24

.19

7

24

.13

0

24

.05

6

23

.96

6

18

.69

5

18

.59

5

18

.50

0

18

.43

3

18

.23

7

18

.15

1

17

.93

1

17

.83

3

17

.72

0

17

.66

6

17

.59

3

16

.96

3

16

.81

9

16

.71

8

16

.64

3

16

.32

1

16

.24

7

16

.14

61

6.0

48

15

.93

1

NH2N

O

N

O

Ph

Ph

2

HN

Ph

O


33

1H and


ppm (t1)0.01.02.03.04.05.06.07.0

32

.06

18

.00

2.4

1

2.0

5

0.5

8

0.4

8

0.2

5

13

.89

5.8

3

ppm (t1)050100150

17

3.5

21

17

3.3

76

17

2.6

81

17

2.2

38

17

2.0

65

17

1.9

75

17

1.8

10

17

1.6

47

17

1.5

83

17

1.3

29

17

1.1

83

17

0.7

09

17

0.5

67

17

0.4

44

17

0.2

73

16

8.9

37

16

8.5

64

16

8.3

11

16

8.0

73

16

7.8

86

16

7.7

32

16

7.6

28

16

7.3

54

14

4.4

51

14

4.2

12

14

0.7

66

14

0.6

22

14

0.4

96

14

0.3

84

14

0.2

92

14

0.2

15

14

0.1

35

14

0.0

22

13

9.9

18

13

9.7

38

13

9.6

17

13

9.4

35

13

9.3

57

13

9.2

47

13

9.1

56

13

9.0

66

13

8.9

54

13

8.5

53

12

8.7

62

12

8.6

43

12

8.4

33

12

8.0

67

12

7.6

99

12

7.5

82

12

7.5

41

12

7.4

37

12

7.2

95

12

7.1

92

12

7.0

69

12

6.7

84

12

6.7

27

12

6.6

33

12

6.5

32

12

6.3

94

58

.50

7

58

.41

9

58

.21

0

57

.98

6

55

.58

3

55

.49

3

55

.21

9

55

.00

2

54

.89

3

54

.78

9

54

.63

2

54

.56

8

54

.43

2

54

.33

5

54

.27

2

54

.04

3

53

.95

5

53

.84

5

53

.78

4

52

.30

2

51

.96

2

51

.90

2

51

.69

4

51

.64

0

51

.56

0

51

.43

8

51

.32

4

50

.99

3

50

.94

0

50

.74

0

48

.83

1

48

.80

1

48

.51

7

48

.47

3

45

.55

9

45

.29

5

45

.12

2

45

.05

0

44

.89

0

44

.84

0

44

.63

2

44

.34

2

44

.17

4

43

.93

2

43

.84

1

41

.18

5

41

.12

0

41

.00

6

40

.74

3

40

.57

3

40

.32

5

40

.29

2

40

.08

1

39

.88

8

39

.69

3

39

.29

3

39

.19

9

39

.11

5

38

.93

7

38

.75

8

36

.53

4

36

.25

8

36

.18

2

35

.86

9

35

.81

1

35

.46

1

35

.36

0

35

.20

6

35

.01

0

34

.90

4

34

.80

0

34

.35

8

34

.18

9

34

.08

3

33

.93

2

33

.79

3

33

.73

5

33

.49

7

33

.40

4

33

.30

7

32

.50

2

32

.29

8

32

.18

2

31

.98

7

24

.39

8

24

.31

0

24

.17

1

23

.95

7

23

.85

9

23

.73

7

18

.70

2

18

.58

3

18

.43

5

18

.34

1

18

.22

5

18

.12

9

18

.03

1

17

.98

9

17

.89

5

17

.66

71

7.4

00

17

.28

61

6.9

50

16

.86

41

6.7

94

16

.69

01

6.5

74

16

.30

21

6.2

21

16

.09

61

6.0

31

15

.90

3

NH2N

O

NH

O

Ph

Ph

3


34

1H and


ppm (t1)0.01.02.03.04.05.06.07.0

10

.86

4.0

0

2.4

1

9.4

5

15

.77

0.4

2

0.5

3

0.3

6

0.6

3

ppm (t1)050100150

17

1.0

63

16

9.9

12

16

8.1

91

15

5.6

61

13

9.6

48

12

8.6

35

12

8.4

47

12

8.2

86

12

7.6

26

12

7.4

74

12

7.1

05

12

6.8

90

12

6.5

22

80

.36

9

79

.97

4

54

.87

6

54

.06

7

53

.09

1

53

.03

4

52

.94

5

51

.70

3

51

.56

9

51

.38

1

45

.25

5

45

.10

9

44

.82

9

39

.23

6

38

.37

3

36

.28

3

34

.21

8

28

.36

5

27

.99

2

27

.92

7

17

.99

0

16

.92

7

16

.47

8

OtBuN

O

Ph

BocN

OPh


35


ppm (t1)050100150

17

4.6

10

17

4.4

75

17

3.6

97

17

3.2

68

17

2.5

13

17

2.3

61

17

1.7

01

16

8.9

86

16

8.9

25

16

8.5

13

16

8.0

57

16

7.9

15

15

5.7

50

15

5.5

99

14

1.9

31

14

1.3

83

14

1.0

54

14

0.5

07

14

0.1

00

13

9.7

25

13

9.5

58

13

9.3

26

13

9.2

26

13

8.9

98

13

8.8

42

12

8.9

36

12

8.7

21

12

8.6

53

12

8.4

29

12

8.3

77

12

8.2

51

12

7.6

72

12

7.5

62

12

7.4

23

12

7.2

50

12

7.0

82

12

6.9

62

12

6.8

15

12

6.7

29

12

6.5

45

81

.21

1

80

.05

4

55

.27

5

55

.17

5

55

.04

8

54

.84

0

54

.78

6

54

.70

9

54

.56

5

54

.37

2

54

.07

9

53

.21

8

53

.13

9

52

.47

7

51

.68

0

51

.54

5

51

.44

4

51

.28

2

50

.99

9

50

.78

6

45

.64

8

45

.45

3

45

.34

3

45

.15

8

44

.95

2

44

.56

8

44

.24

1

43

.93

9

43

.74

9

40

.80

4

39

.98

2

39

.70

3

38

.95

7

38

.79

2

38

.35

8

34

.83

5

34

.61

9

34

.36

3

33

.79

8

33

.50

4

33

.18

4

28

.32

0

18

.65

7

18

.52

9

18

.34

7

18

.26

7

18

.02

5

17

.93

4

17

.72

1

17

.62

5

17

.38

4

17

.22

4

17

.09

1

16

.85

0

16

.62

1

16

.44

2

16

.36

7

16

.17

3

16

.02

4

OtBuN

O

Ph

BocN

OPh


36

1H and


ppm (t1)0.01.02.03.04.05.06.07.0

20

.83

1.2

1

0.5

9

0.5

9

1.2

1

7.7

4

3.9

4

30

.00

ppm (f1)050100150

17

2.3

47

17

2.2

76

17

1.6

07

17

1.4

04

17

1.2

00

17

1.0

85

17

0.9

55

17

0.8

40

17

0.6

66

17

0.5

69

17

0.4

18

17

0.3

51

17

0.0

82

17

0.0

01

16

9.5

99

16

9.1

55

16

8.5

83

16

8.3

99

16

8.0

14

16

7.8

64

16

7.3

15

16

7.1

57

16

6.9

96

15

5.7

20

15

5.6

45

15

5.5

06

14

1.3

64

14

1.2

71

14

0.8

90

14

0.8

02

14

0.6

78

14

0.5

73

14

0.2

89

13

9.9

35

13

9.6

99

13

9.4

43

13

9.2

46

13

9.0

04

12

8.9

21

12

8.7

62

12

8.6

29

12

8.3

85

12

8.2

43

12

8.0

29

12

7.5

98

12

7.5

08

12

7.4

57

12

7.3

44

12

7.1

32

12

7.0

51

12

6.9

14

12

6.7

61

12

6.6

70

12

6.4

24

12

6.2

34

80

.34

8

79

.86

4

79

.78

8

55

.35

5

55

.08

6

54

.71

1

54

.50

4

54

.24

6

54

.14

1

53

.98

8

53

.89

5

53

.19

5

52

.84

7

52

.77

2

51

.85

3

51

.67

2

51

.48

6

51

.26

2

51

.18

5

50

.82

6

45

.59

1

45

.53

5

45

.22

4

45

.03

8

44

.94

9

44

.59

4

44

.14

9

43

.97

8

40

.63

6

40

.08

6

39

.62

9

39

.52

6

39

.27

2

39

.05

7

38

.49

6

38

.33

1

36

.23

4

36

.18

0

35

.75

0

35

.65

0

34

.17

0

34

.09

5

33

.85

8

33

.62

3

33

.33

8

33

.25

4

28

.31

7

27

.97

0

27

.89

6

18

.64

7

18

.45

2

18

.40

6

18

.28

7

18

.08

7

17

.87

0

17

.76

7

17

.17

3

17

.10

4

16

.43

6

16

.23

3

16

.01

7

15

.88

5

15

.79

2

OtBuN

O

NBoc

O

Ph

Ph

2


37

1H and


ppm (t1)0.01.02.03.04.05.06.07.0

2.5

6

2.7

7

30

.00

11

.22

37

.15

5.6

7

ppm (f1)050100150

17

2.3

50

17

1.5

29

17

1.3

48

17

1.1

56

17

1.1

00

17

0.7

22

17

0.6

62

17

0.3

15

17

0.0

09

16

9.5

55

16

8.9

36

16

8.8

61

16

8.5

46

16

8.3

52

16

8.1

44

16

7.8

81

16

7.7

10

16

7.3

11

16

7.0

97

16

7.0

15

15

5.6

90

15

5.6

15

15

5.4

94

14

1.3

83

14

1.3

11

14

1.1

89

14

0.8

11

14

0.5

60

14

0.3

43

14

0.1

14

13

9.7

58

13

9.3

80

13

9.1

98

13

8.9

29

12

8.8

40

12

8.7

95

12

8.5

91

12

8.3

69

12

8.2

37

12

8.1

86

12

7.5

55

12

7.4

67

12

7.3

96

12

7.0

24

12

6.8

61

12

6.7

40

12

6.6

70

12

6.4

79

12

6.3

85

12

6.3

05

79

.85

3

79

.74

2

79

.58

7

55

.65

8

55

.49

7

55

.25

5

55

.03

6

54

.54

5

54

.47

3

54

.18

5

53

.29

6

53

.17

0

51

.79

3

51

.62

2

51

.46

8

51

.40

9

51

.22

6

51

.12

8

50

.85

5

50

.78

9

50

.68

5

45

.50

0

44

.93

4

44

.76

0

44

.66

2

44

.48

3

44

.19

7

44

.03

2

43

.91

9

40

.70

8

40

.57

4

40

.26

8

40

.07

1

39

.38

6

39

.23

2

39

.12

4

38

.99

9

38

.46

4

38

.25

2

36

.20

5

35

.59

3

34

.15

7

33

.95

2

33

.54

1

33

.44

5

33

.26

8

33

.18

2

28

.30

1

27

.94

4

27

.88

3

27

.31

8

18

.80

4

18

.67

8

18

.56

6

18

.38

7

18

.27

4

18

.18

2

18

.06

6

18

.00

9

17

.87

1

17

.68

9

17

.18

9

17

.07

1

16

.42

3

16

.30

8

16

.15

2

15

.97

6

15

.86

6

15

.77

5

OtBuN

O

NBoc

O

Ph

Ph

3


38

1H and


ppm (t1)0.01.02.03.04.05.06.07.0

10

.75

0.6

2

2.4

3

0.6

8

2.1

7

15

.00

3.8

9

ppm (t1)050100150

17

3.9

08

17

3.7

43

16

9.0

75

16

8.7

48

15

5.7

64

15

5.6

49

14

1.5

51

14

1.4

40

14

1.3

60

14

1.2

85

13

9.3

04

12

8.7

05

12

8.4

71

12

8.3

08

12

7.8

09

12

7.5

12

12

7.2

02

12

6.8

17

12

6.6

66

12

6.6

23

80

.46

5

80

.27

2

80

.12

3

80

.00

0

79

.91

5

79

.83

4

55

.09

7

54

.98

5

54

.38

6

54

.20

9

53

.97

6

53

.15

9

52

.86

0

52

.78

1

52

.71

1

51

.63

9

51

.54

0

51

.44

1

45

.65

5

45

.53

2

45

.41

8

45

.33

8

45

.00

9

44

.88

1

44

.84

4

40

.11

5

38

.77

1

36

.10

6

35

.91

8

35

.85

9

35

.78

2

35

.65

2

35

.55

3

35

.50

8

28

.36

2

18

.13

1

17

.84

0

16

.32

7

NH2N

O

Ph

BocN

OPh


39


ppm (t1)050100150

17

4.6

10

17

4.4

75

17

3.6

97

17

3.2

68

17

2.5

13

17

2.3

61

17

1.7

01

16

8.9

86

16

8.9

25

16

8.5

13

16

8.0

57

16

7.9

15

15

5.7

50

15

5.5

99

14

1.9

31

14

1.3

83

14

1.0

54

14

0.5

07

14

0.1

00

13

9.7

25

13

9.5

58

13

9.3

26

13

9.2

26

13

8.9

98

13

8.8

42

12

8.9

36

12

8.7

21

12

8.6

53

12

8.4

29

12

8.3

77

12

8.2

51

12

7.6

72

12

7.5

62

12

7.4

23

12

7.2

50

12

7.0

82

12

6.9

62

12

6.8

15

12

6.7

29

12

6.5

45

81

.21

1

80

.05

4

55

.27

5

55

.17

5

55

.04

8

54

.84

0

54

.78

6

54

.70

9

54

.56

5

54

.37

2

54

.07

9

53

.21

8

53

.13

9

52

.47

7

51

.68

0

51

.54

5

51

.44

4

51

.28

2

50

.99

9

50

.78

6

45

.64

8

45

.45

3

45

.34

3

45

.15

8

44

.95

2

44

.56

8

44

.24

1

43

.93

9

43

.74

9

40

.80

4

39

.98

2

39

.70

3

38

.95

7

38

.79

2

38

.35

8

34

.83

5

34

.61

9

34

.36

3

33

.79

8

33

.50

4

33

.18

4

28

.32

0

18

.65

7

18

.52

9

18

.34

7

18

.26

7

18

.02

5

17

.93

4

17

.72

1

17

.62

5

17

.38

4

17

.22

4

17

.09

1

16

.85

0

16

.62

1

16

.44

2

16

.36

7

16

.17

3

16

.02

4

NH2N

O

Ph

BocN

OPh


40

1H and


ppm (t1)0.01.02.03.04.05.06.07.0

21

.24

21

.00

4.1

9

7.5

8

1.3

4

0.1

5

1.4

5

2.0

3

ppm (t1)050100150

17

4.3

39

17

4.0

42

17

2.2

09

17

1.7

66

17

1.5

02

17

1.3

69

16

9.2

48

16

8.9

50

16

8.7

01

16

8.5

59

16

8.0

10

16

7.8

11

16

7.6

11

15

5.8

67

15

5.6

80

15

5.5

37

14

1.3

45

14

1.1

48

14

1.0

43

14

0.6

86

14

0.4

66

13

9.6

19

13

9.5

13

13

9.1

96

12

8.9

21

12

8.8

02

12

8.6

89

12

8.6

12

12

8.5

17

12

8.3

93

12

8.3

28

12

8.2

04

12

8.1

10

12

7.8

06

12

7.6

51

12

7.5

44

12

7.3

80

12

7.3

10

12

7.2

79

12

7.0

55

12

6.9

63

12

6.7

52

12

6.6

33

12

6.3

73

80

.55

9

80

.12

3

79

.99

8

79

.82

0

55

.21

8

55

.04

4

54

.91

2

54

.63

4

54

.54

2

54

.40

6

54

.32

9

51

.95

2

51

.48

8

51

.39

3

51

.00

0

50

.90

6

45

.27

5

45

.17

0

45

.08

1

44

.95

8

44

.45

2

44

.20

4

43

.98

6

41

.10

5

40

.92

7

40

.08

3

39

.95

0

38

.99

5

38

.80

5

36

.30

1

35

.87

1

35

.39

2

35

.25

5

34

.99

7

33

.60

8

33

.37

3

28

.35

4

28

.31

6

18

.25

8

17

.92

3

17

.66

5

16

.71

4

16

.24

4

16

.03

8

NH2N

O

NBoc

O

Ph

Ph

2


41

1H and


ppm (t1)0.01.02.03.04.05.06.07.0

6.5

8

0.1

5

32

.91

11

.76

6.3

2

27

.00

ppm (t1)050100150

17

2.7

48

17

2.5

60

17

2.2

78

17

1.9

00

17

1.8

16

17

1.6

69

17

1.5

94

17

1.3

93

17

1.2

65

16

8.9

21

16

8.5

99

16

8.3

94

16

8.1

41

16

7.9

29

16

7.6

95

16

7.4

79

15

5.6

25

14

1.3

55

14

0.9

68

14

0.8

11

14

0.6

93

14

0.5

45

14

0.2

96

14

0.1

95

13

9.8

92

13

9.4

97

13

9.3

76

13

9.1

18

13

9.0

14

12

8.7

45

12

8.6

46

12

8.5

06

12

8.4

35

12

8.3

66

12

8.2

20

12

7.9

23

12

7.7

03

12

7.6

16

12

7.5

36

12

7.4

24

12

7.3

36

12

7.1

47

12

7.1

01

12

6.9

54

12

6.8

48

12

6.7

48

12

6.6

23

12

6.4

60

12

6.4

21

80

.08

7

80

.03

0

79

.93

7

79

.88

6

79

.77

5

55

.60

7

55

.52

4

55

.43

7

55

.25

9

55

.14

2

55

.05

7

54

.89

5

54

.81

2

54

.70

4

54

.49

7

54

.40

7

54

.35

4

54

.18

5

54

.03

4

53

.90

8

53

.82

8

53

.75

3

53

.67

6

53

.33

0

53

.26

2

53

.20

6

53

.13

6

52

.35

0

52

.29

3

52

.11

0

51

.98

8

51

.70

5

51

.54

5

51

.46

3

51

.07

8

50

.99

2

50

.81

6

50

.57

4

50

.50

5

45

.49

0

45

.31

2

45

.24

7

45

.16

3

45

.09

3

45

.02

1

44

.90

1

44

.75

8

44

.71

9

44

.62

3

44

.50

7

44

.42

7

44

.31

3

44

.07

4

43

.96

9

40

.92

2

40

.85

1

40

.67

4

40

.61

4

40

.21

3

40

.03

5

39

.87

0

39

.38

1

39

.21

1

39

.01

8

38

.92

9

38

.80

5

38

.70

4

38

.37

5

36

.26

7

36

.10

2

35

.88

2

35

.80

5

35

.66

0

35

.56

1

35

.38

2

35

.17

7

34

.97

9

34

.35

6

34

.16

0

33

.95

4

33

.84

2

33

.70

0

33

.62

8

33

.57

2

33

.48

4

33

.26

5

32

.36

7

32

.26

0

32

.09

9

31

.94

9

31

.79

3

29

.18

4

28

.31

5

18

.75

1

18

.65

4

18

.51

9

18

.26

0

18

.13

0

17

.91

9

17

.81

71

7.6

56

17

.42

11

6.9

83

16

.87

71

6.7

67

16

.63

91

6.3

18

16

.09

0

NH2N

O

NBoc

O

Ph

Ph

3


42

1H and


ppm (t1)0.01.02.03.04.05.06.07.0

0.0

4

0.3

6

0.5

0

0.9

5

1.8

8

10

.55

1.9

3

2.0

0

0.0

6

2.8

7

3.0

2

ppm (t1)050100150

17

4.8

71

17

3.5

18

16

5.4

63

16

5.0

61

16

2.0

74

16

1.7

36

16

1.3

69

16

0.9

97

13

8.7

36

13

8.0

96

13

5.0

70

13

5.0

15

12

9.7

00

12

9.6

64

12

9.3

76

12

9.3

30

12

8.9

30

12

8.6

64

12

8.2

65

12

8.0

49

12

7.9

67

12

7.1

65

12

6.5

70

11

7.4

74

11

4.5

83

59

.20

9

59

.12

8

55

.09

8

53

.12

4

46

.02

3

39

.43

1

39

.04

6

33

.81

4

33

.36

5

19

.58

3

19

.32

0

17

.53

9

16

.28

0

OHN

O

Ph

TFA.HN

OPh


43


ppm (t1)050100150

17

4.6

10

17

4.4

75

17

3.6

97

17

3.2

68

17

2.5

13

17

2.3

61

17

1.7

01

16

8.9

86

16

8.9

25

16

8.5

13

16

8.0

57

16

7.9

15

15

5.7

50

15

5.5

99

14

1.9

31

14

1.3

83

14

1.0

54

14

0.5

07

14

0.1

00

13

9.7

25

13

9.5

58

13

9.3

26

13

9.2

26

13

8.9

98

13

8.8

42

12

8.9

36

12

8.7

21

12

8.6

53

12

8.4

29

12

8.3

77

12

8.2

51

12

7.6

72

12

7.5

62

12

7.4

23

12

7.2

50

12

7.0

82

12

6.9

62

12

6.8

15

12

6.7

29

12

6.5

45

81

.21

1

80

.05

4

55

.27

5

55

.17

5

55

.04

8

54

.84

0

54

.78

6

54

.70

9

54

.56

5

54

.37

2

54

.07

9

53

.21

8

53

.13

9

52

.47

7

51

.68

0

51

.54

5

51

.44

4

51

.28

2

50

.99

9

50

.78

6

45

.64

8

45

.45

3

45

.34

3

45

.15

8

44

.95

2

44

.56

8

44

.24

1

43

.93

9

43

.74

9

40

.80

4

39

.98

2

39

.70

3

38

.95

7

38

.79

2

38

.35

8

34

.83

5

34

.61

9

34

.36

3

33

.79

8

33

.50

4

33

.18

4

28

.32

0

18

.65

7

18

.52

9

18

.34

7

18

.26

7

18

.02

5

17

.93

4

17

.72

1

17

.62

5

17

.38

4

17

.22

4

17

.09

1

16

.85

0

16

.62

1

16

.44

2

16

.36

7

16

.17

3

16

.02

4


44

1H and


ppm (t1)0.01.02.03.04.05.06.07.0

3.5

2

12

.00

1.3

7

20

.27

1.3

8

8.4

0

ppm (t1)050100150

17

4.7

30

17

4.6

40

17

3.4

76

17

3.2

33

17

2.5

87

17

2.2

47

17

1.8

40

17

1.5

12

17

0.8

61

16

8.5

27

16

8.3

32

16

8.1

65

16

7.9

25

16

5.4

95

16

5.3

66

16

4.7

71

16

1.4

86

16

1.1

15

14

0.4

96

14

0.4

00

14

0.0

79

14

0.0

27

13

9.5

56

13

9.3

89

13

9.2

62

13

9.1

23

13

8.7

16

13

5.1

75

13

5.0

42

13

4.9

82

13

4.9

01

13

4.7

93

12

9.9

72

12

9.8

19

12

9.7

61

12

9.6

70

12

9.5

93

12

9.4

36

12

9.3

67

12

9.0

15

12

8.9

32

12

8.8

35

12

8.6

63

12

8.5

71

12

8.4

16

12

8.3

39

12

8.1

69

12

7.9

62

12

7.8

91

12

7.7

98

12

7.6

84

12

7.5

84

12

7.5

32

12

7.4

42

12

7.3

53

12

7.1

06

12

6.7

26

12

6.6

10

12

6.5

22

12

6.3

87

12

6.2

32

12

0.2

56

11

7.3

65

11

4.4

90

11

1.6

07

59

.19

4

59

.11

1

58

.97

7

55

.96

7

55

.52

7

55

.43

9

55

.30

2

55

.17

8

55

.13

8

55

.00

2

54

.54

2

53

.51

8

53

.16

6

52

.95

6

52

.89

8

51

.47

5

51

.40

3

51

.28

2

46

.05

7

46

.01

4

45

.92

3

45

.75

0

45

.67

5

45

.56

6

45

.45

7

45

.33

7

45

.24

7

45

.10

9

45

.04

4

44

.74

7

44

.54

5

44

.44

3

44

.22

6

44

.02

4

41

.30

1

41

.09

7

40

.68

7

40

.62

4

40

.37

9

40

.20

4

40

.10

5

40

.00

7

39

.84

1

39

.42

6

39

.34

9

39

.26

1

39

.14

2

39

.01

2

38

.93

6

38

.68

1

34

.43

7

34

.02

4

33

.87

0

33

.75

7

33

.58

9

32

.58

2

32

.29

4

31

.82

2

19

.89

2

19

.59

3

19

.47

2

19

.41

2

19

.33

5

18

.54

5

18

.43

9

18

.13

4

18

.05

5

17

.77

4

17

.71

4

16

.93

2

16

.53

2

16

.27

7

16

.13

9

16

.04

9

OHN

O

NTFA.H

O

Ph

Ph

2


45

1H NMR spectrum of compound 15 (CDCl3)

ppm (t1)0.01.02.03.04.05.06.07.0

18

.00

2.1

9

30

.69

5.4

8

2.7

1

12

.18

ppm (t1)050100150

17

4.6

10

17

4.4

75

17

3.6

97

17

3.2

68

17

2.5

13

17

2.3

61

17

1.7

01

16

8.9

86

16

8.9

25

16

8.5

13

16

8.0

57

16

7.9

15

15

5.7

50

15

5.5

99

14

1.9

31

14

1.3

83

14

1.0

54

14

0.5

07

14

0.1

00

13

9.7

25

13

9.5

58

13

9.3

26

13

9.2

26

13

8.9

98

13

8.8

42

12

8.9

36

12

8.7

21

12

8.6

53

12

8.4

29

12

8.3

77

12

8.2

51

12

7.6

72

12

7.5

62

12

7.4

23

12

7.2

50

12

7.0

82

12

6.9

62

12

6.8

15

12

6.7

29

12

6.5

45

81

.21

1

80

.05

4

55

.27

5

55

.17

5

55

.04

8

54

.84

0

54

.78

6

54

.70

9

54

.56

5

54

.37

2

54

.07

9

53

.21

8

53

.13

9

52

.47

7

51

.68

0

51

.54

5

51

.44

4

51

.28

2

50

.99

9

50

.78

6

45

.64

8

45

.45

3

45

.34

3

45

.15

8

44

.95

2

44

.56

8

44

.24

1

43

.93

9

43

.74

9

40

.80

4

39

.98

2

39

.70

3

38

.95

7

38

.79

2

38

.35

8

34

.83

5

34

.61

9

34

.36

3

33

.79

8

33

.50

4

33

.18

4

28

.32

0

18

.65

7

18

.52

9

18

.34

7

18

.26

7

18

.02

5

17

.93

4

17

.72

1

17

.62

5

17

.38

4

17

.22

4

17

.09

1

16

.85

0

16

.62

1

16

.44

2

16

.36

7

16

.17

3

16

.02

4

OHN

O

NTFA.H

O

Ph

Ph

3


46

1H and


ppm (t1)0.01.02.03.04.05.06.07.0

21

.00

3.7

1

7.4

0

21

.47

0.1

3

0.6

6

1.6

1

0.6

0

1.4

7

ppm (t1)050100150

17

4.6

10

17

4.4

75

17

3.6

97

17

3.2

68

17

2.5

13

17

2.3

61

17

1.7

01

16

8.9

86

16

8.9

25

16

8.5

13

16

8.0

57

16

7.9

15

15

5.7

50

15

5.5

99

14

1.9

31

14

1.3

83

14

1.0

54

14

0.5

07

14

0.1

00

13

9.7

25

13

9.5

58

13

9.3

26

13

9.2

26

13

8.9

98

13

8.8

42

12

8.9

36

12

8.7

21

12

8.6

53

12

8.4

29

12

8.3

77

12

8.2

51

12

7.6

72

12

7.5

62

12

7.4

23

12

7.2

50

12

7.0

82

12

6.9

62

12

6.8

15

12

6.7

29

12

6.5

45

81

.21

1

80

.05

4

55

.27

5

55

.17

5

55

.04

8

54

.84

0

54

.78

6

54

.70

9

54

.56

5

54

.37

2

54

.07

9

53

.21

8

53

.13

9

52

.47

7

51

.68

0

51

.54

5

51

.44

4

51

.28

2

50

.99

9

50

.78

6

45

.64

8

45

.45

3

45

.34

3

45

.15

8

44

.95

2

44

.56

8

44

.24

1

43

.93

9

43

.74

9

40

.80

4

39

.98

2

39

.70

3

38

.95

7

38

.79

2

38

.35

8

34

.83

5

34

.61

9

34

.36

3

33

.79

8

33

.50

4

33

.18

4

28

.32

0

18

.65

7

18

.52

9

18

.34

7

18

.26

7

18

.02

5

17

.93

4

17

.72

1

17

.62

5

17

.38

4

17

.22

4

17

.09

1

16

.85

0

16

.62

1

16

.44

2

16

.36

7

16

.17

3

16

.02

4

OHN

O

NBoc

O

Ph

Ph

2


47

1H and


ppm (t1)0.01.02.03.04.05.06.07.0

41

.24

3.4

8

3.9

5

15

.65

7.5

2

42

.00

ppm (f1)050100150

17

2.2

00

17

2.1

23

17

1.9

87

17

1.8

28

17

1.5

41

17

1.4

72

17

1.2

09

17

1.0

06

17

0.9

12

17

0.8

18

17

0.5

25

17

0.1

96

16

9.8

73

16

9.5

00

16

9.4

29

16

9.3

04

16

8.8

22

16

8.7

67

16

8.6

71

16

8.6

07

16

8.3

82

16

8.3

34

16

8.2

05

16

8.1

02

16

7.9

72

16

7.9

34

16

7.7

51

16

7.5

95

16

7.2

91

16

7.1

93

16

7.1

01

16

6.8

68

16

6.8

19

15

5.4

83

15

5.3

72

14

1.1

68

14

1.0

59

14

0.9

48

14

0.6

96

14

0.6

29

14

0.4

34

14

0.2

97

14

0.1

60

14

0.0

29

13

9.8

61

13

9.7

56

13

9.6

39

13

9.5

94

13

9.4

68

13

9.4

20

13

9.2

82

13

9.1

56

13

8.9

84

12

8.4

63

12

8.2

51

12

8.1

17

12

7.8

23

12

7.4

41

12

7.3

47

12

7.2

60

12

7.2

02

12

7.0

04

12

6.9

15

12

6.6

22

12

6.2

66

12

6.1

81

79

.71

4

79

.57

1

55

.63

9

55

.54

6

55

.37

2

55

.31

9

55

.15

8

54

.94

1

54

.81

6

54

.52

4

54

.30

6

54

.24

9

54

.15

2

54

.06

4

53

.30

7

53

.20

9

53

.04

8

51

.64

5

51

.50

1

51

.33

6

51

.21

4

51

.15

8

51

.07

2

51

.02

7

50

.92

5

50

.66

6

50

.56

5

45

.37

0

44

.83

6

44

.68

3

44

.49

2

44

.38

0

44

.31

4

44

.19

1

44

.16

0

44

.07

1

43

.96

9

43

.82

6

40

.61

2

40

.44

7

40

.14

4

40

.07

6

39

.94

4

39

.70

0

39

.47

0

39

.29

8

39

.11

1

38

.98

7

38

.88

6

38

.77

6

38

.45

0

38

.32

9

38

.14

4

38

.05

6

36

.02

6

35

.92

7

35

.78

8

35

.45

1

34

.02

9

33

.82

1

33

.71

9

33

.41

9

33

.34

0

33

.17

9

33

.03

1

32

.91

5

32

.41

7

32

.17

9

31

.91

3

28

.18

0

27

.82

1

27

.76

1

19

.13

2

19

.08

3

19

.00

1

18

.91

9

18

.65

8

18

.59

9

18

.47

4

18

.38

1

18

.24

9

18

.07

2

18

.01

4

17

.92

2

17

.73

5

17

.60

8

17

.12

4

16

.95

8

16

.70

9

16

.60

4

16

.30

01

6.1

86

16

.05

11

5.8

61

OtBuN

O

NBoc

O

Ph

Ph

4


48

1H and


ppm (t1)0.01.02.03.04.05.06.07.0

4.4

2

4.8

4

52

.13

19

.28

9.8

9

48

.00

ppm (t1)050100150

17

2.3

72

17

2.3

15

17

2.2

00

17

2.1

01

17

1.9

58

17

1.6

42

17

1.5

24

17

1.4

13

17

1.3

24

17

1.1

11

17

1.0

23

17

0.9

21

17

0.7

19

17

0.6

67

17

0.6

02

17

0.5

27

17

0.2

87

16

9.9

75

16

9.5

33

16

8.5

86

16

8.4

62

16

8.1

96

16

8.0

81

16

7.8

56

16

7.7

82

16

7.6

92

16

7.5

23

16

7.3

56

16

7.3

02

16

7.1

99

16

7.1

48

16

6.9

84

16

6.9

07

15

5.6

80

15

5.5

98

15

5.5

05

14

1.5

23

14

1.3

03

14

1.1

78

14

1.0

53

14

0.8

08

14

0.6

32

14

0.5

42

14

0.4

78

14

0.2

88

14

0.1

69

14

0.0

32

13

9.7

13

13

9.5

75

13

9.4

10

13

9.2

63

13

9.0

78

13

8.9

91

12

8.5

77

12

8.3

54

12

7.9

44

12

7.5

47

12

7.4

64

12

7.3

22

12

7.0

03

12

6.7

07

12

6.6

54

12

6.3

69

12

6.2

85

79

.87

8

79

.72

3

79

.59

1

55

.46

7

55

.27

6

55

.14

2

55

.04

4

54

.89

7

54

.68

3

54

.55

0

54

.42

2

54

.14

5

53

.93

6

53

.26

7

53

.15

9

51

.76

0

51

.60

3

51

.40

3

51

.26

5

51

.12

2

51

.01

3

50

.77

3

50

.66

1

45

.46

1

45

.15

1

44

.92

6

44

.78

5

44

.55

1

44

.47

4

44

.39

8

44

.22

9

44

.10

1

43

.90

6

40

.76

8

40

.55

9

40

.11

6

40

.03

6

39

.91

9

39

.42

5

39

.20

1

39

.10

0

38

.99

8

38

.78

6

38

.46

3

38

.24

3

36

.16

2

36

.11

6

35

.56

8

34

.14

3

33

.93

3

33

.41

6

33

.32

1

32

.38

0

32

.31

3

32

.16

2

28

.28

7

27

.92

9

27

.86

8

19

.24

6

19

.11

7

18

.97

3

18

.85

4

18

.71

1

18

.57

4

18

.40

9

18

.33

1

18

.17

2

18

.05

6

17

.87

4

17

.80

4

17

.72

1

17

.48

5

17

.17

5

17

.05

6

16

.41

3

16

.29

5

16

.14

6

15

.96

2

OtBuN

O

NBoc

O

Ph

Ph

5


49

1H and


ppm (t1)0.01.02.03.04.05.06.07.0

33

.00

41

.63

8.1

8

15

.00

8.3

3

ppm (t1)050100150

17

2.4

41

17

2.2

33

17

1.7

15

17

1.4

40

17

1.2

37

17

0.7

45

16

8.7

39

16

8.5

04

16

8.1

00

16

7.9

48

16

7.7

10

16

7.3

67

16

7.0

03

15

5.6

46

14

0.9

65

14

0.8

58

14

0.7

31

14

0.6

70

14

0.5

16

14

0.2

75

14

0.1

47

14

0.0

27

13

9.7

14

13

9.4

85

13

9.3

56

13

9.1

12

13

9.0

23

12

8.5

93

12

8.4

99

12

8.4

09

12

8.3

58

12

8.1

80

12

7.5

89

12

7.3

79

12

7.1

36

12

7.0

27

12

6.8

64

12

6.7

03

12

6.6

21

12

6.4

42

79

.86

4

79

.81

4

79

.73

6

55

.58

8

55

.46

9

55

.36

9

55

.20

8

55

.08

1

55

.03

9

54

.92

3

54

.80

0

54

.66

8

54

.49

9

54

.35

0

54

.30

1

54

.08

2

53

.94

2

52

.00

2

51

.88

4

51

.75

0

51

.58

9

51

.49

4

51

.39

9

51

.28

8

51

.19

0

51

.15

1

51

.00

5

50

.81

5

45

.62

0

45

.53

5

45

.44

5

45

.29

8

45

.25

2

45

.12

1

44

.94

9

44

.90

2

44

.59

4

44

.48

9

44

.39

0

44

.28

9

44

.16

6

44

.10

7

43

.97

7

43

.77

9

41

.19

0

40

.95

1

40

.87

5

40

.73

1

40

.63

5

40

.59

0

40

.42

5

40

.06

2

39

.94

4

39

.85

4

39

.39

7

39

.21

4

39

.11

5

39

.01

0

38

.96

1

38

.87

4

38

.84

1

38

.67

9

34

.00

7

33

.83

0

33

.76

3

33

.58

1

33

.47

5

33

.32

4

32

.20

0

32

.06

7

31

.91

2

31

.75

3

28

.29

3

18

.26

4

18

.16

1

18

.08

6

18

.02

6

17

.85

1

17

.68

4

17

.34

3

17

.09

2

17

.01

9

16

.93

6

16

.80

9

16

.73

1

16

.51

1

16

.24

9

16

.10

3

16

.01

1

NH2N

O

NBoc

O

Ph

Ph

4


50

1H NMR spectrum of compound 20 (CDCl3)

ppm (t1)0.01.02.03.04.05.06.07.0

39

.00

9.8

0

18

.97

5.5

0

4.7

2

52

.14

NH2N

O

NBoc

O

Ph

Ph

5


51

Analytical HPLC analysis of peptoids

General conditions: Solvent A: water (1% TFA); solvent B: MeCN; solvent C: MeOH; 214 nm.

0,0 5,0 10,0 15,0 20,0 25,0 30,0

-100

200

400

600

900060708 #130 [modified by Administrateur] 51 UV_VIS_1mAU

min

1 - 6,677

WVL:214 nm

Peptoid 1 (A/B 40:60, flow = 0.80). Peptoid 1a (A/B 40:60, flow = 0.80).

0,0 5,0 10,0 15,0 20,0 25,0 30,0 35,0 40,0 45,0

-50

100

200

300


min

1 - 23,424

WVL:214 nm

Peptoid 2 (A/B 40:60, flow = 0.80). Peptoid 2a (A/B 30:70, flow = 0.80).

0,0 10,0 20,0 30,0 40,0 50,0

-50

0

50

100

150

200

250060708 #98 [modified by Administrateur] 68-1-3 UV_VIS_1mAU

min

1 - 27,262

WVL:214 nm

Peptoid 3 (A/B 30:70, flow = 0.80). Peptoid 4 (A/C 40:60, flow = 0.40).

0,0 5,0 10,0 15,0 20,0 25,0 30,0 35,0

-50

100

200

300


min

1 - 13,919

WVL:214 nm

0,0 5,0 10,0 15,0 20,0 25,0 30,0 35,0 40,0

-50

100

200

300


min

1 - 16,233

WVL:214 nm

0,0 5,0 10,0 15,0 20,0 25,0 30,0 35,0

-200

0

250

500

750

1 000

1 400060708 #220 [modified by Administrateur] 92 UV_VIS_1mAU

min

1 - 11,174

WVL:214 nm


52

0,0 5,0 10,0 15,0 20,0 25,0 30,0

-200

500

1 000

1 500


min

1 - 9,209

WVL:214 nm

Peptoid 4a (A/C 30:70, flow = 0.50). Peptoid 5 (A/C 30:70, flow = 0.50).

0,0 10,0 20,0 30,0 40,0 55,0

-100

0

100

200

300

400

500


min

1 - 30,685

WVL:214 nm

Peptoid 5a (A/C 30:70, flow = 0.50). Peptoid 6 (A/C 20:80, flow = 0.60).

0,0 5,0 10,0 15,0 20,0 25,0 30,0 35,0 40,0

-100

0

125

250

375

500

700060708 #128 [modified by Administrateur] 53-4-1 UV_VIS_1mAU

min

1 - 16,180

WVL:214 nm

Peptoid 7 (A/B 20:80, flow = 0.80). Peptoid 8 (A/B 20:80, flow = 0.80).

0,0 5,0 10,0 15,0 20,0 25,0 30,0 35,0

-200

250

500

750

1 000

1 250


min

1 - 14,493

WVL:214 nm

0,0 5,0 10,0 15,0 20,0 25,0 30,0 35,0

-200

0

250

500

750

1 000


min

1 - 11,918

WVL:214 nm

0,0 10,0 20,0 30,0 40,0 50,0

-100

0

100

200

300

400

500


min

1 - 29,422WVL:214 nm


53

0,0 5,0 10,0 15,0 20,0 25,0 30,0 35,0 40,0

-100

0

100

200

300

400

500


min

1 - 17,815

WVL:214 nm

Peptoid 9 (A/B 10:90, flow = 0.80). Peptoid 10 (A/C 20:80, flow = 0.60).

0,0 10,0 20,0 30,0 40,0 50,0

-100

200

400

600


min

1 - 26,556

WVL:214 nm

Peptoid 11 (A/C 20:80, flow = 0.60). Peptoid 12 (A/C 10:90, flow = 0.75).

0,0 5,0 10,0 15,0 20,0 25,0 30,0

-200

250

500

750

1 000

1 250

1 600060708 #281 [modified by Administrateur] 111-1 UV_VIS_1mAU

min

1 - 7,230

WVL:214 nm


0,0 5,0 10,0 15,0 20,0 25,0 30,0 35,0

-200

0

250

500

750

1 000


min

1 - 11,116

WVL:214 nm

0,0 5,0 10,0 15,0 20,0 25,0 30,0 35,0

-200

0

250

500

750

1 000


min

1 - 10,252

WVL:214 nm

0,0 5,0 10,0 15,0 20,0 25,0 30,0

-200

0

250

500

750

1 000


min

1 - 7,063

WVL:214 nm


54

0,0 5,0 10,0 15,0 20,0 25,0 30,0 35,0

-100

200

400

600

800


min

1 - 13,553

WVL:214 nm

Peptoid 15 (A/C 20:80, flow = 0.60). Peptoid 16 (A/B 30:70, flow = 0.80).

0,0 5,0 10,0 15,0 20,0 25,0 30,0 35,0

-100

200

400

600

800

1 000060708 #190 [modified by Administrateur] UV_VIS_1mAU

min

1 - 12,650

WVL:214 nm

Peptoid 17 (A/C 5:95, flow = 0.80). Peptoid 17 after purification by preparative

HPLC (A/C 5:95, flow = 0.80).

0,0 5,0 10,0 15,0 20,0 25,0 30,0 35,0 40,0

-100

200

400

600

800


min

1 - 17,041WVL:214 nm

Peptoid 18 (A/C 5:95, flow = 0.80). Peptoid 18 after purification by preparative

HPLC (A/C 5:95, flow = 0.80).

0,0 5,0 10,0 15,0 20,0 25,0 30,0 35,0 40,0

-100

0

100

200

300

400

500

600060708 #85 [modified by Administrateur] 56-2 UV_VIS_1mAU

min

1 - 17,460

WVL:214 nm

0,0 5,0 10,0 15,0 20,0 25,0 30,0 35,0

-200

0

250

500

750

1 000


min

1 - 10,416

WVL:214 nm

0,0 5,0 10,0 15,0 20,0 25,0 30,0 35,0

-100

200

400

600

900060708 #254 [modified by Administrateur] 75-HPLC UV_VIS_1mAU

min

1 - 14,358

WVL:214 nm


55

0,0 5,0 10,0 15,0 20,0 25,0 30,0 35,0

-100

200

400

600

800


min

1 - 14,891

WVL:214 nm


References

1 Chemical Rubber Co, Robinson, James W, Handbook of spectroscopy, Boca Raton, Fla.

CRC Press 1974.

2 Kamlet MJ, Abboud JL, Abraham MH and Taft RW (1983) Linear solvation energy

relationships. 23. A comprehensive collection of the solvatochromic parameters, π*, α and β

and some methods for simplifying the generalized solvatochromic equation. J Org Chem 48:

2877-2887.

3 Kamlet MJ, Doherty RM, Abraham MH, Marcus Y and Taft RW (1988) Linear solvation

energy relationship. 46. An improved equation for correlation and prediction of octanol/water

partition coefficients of organic nonelectrolytes (including strong hydrogen bond donor

solutes). J Phys Chem 92: 5244-5255.

4 Besseau F, Laurence C and Berthelot M (1994) Hydrogen-bond basicity of esters, lactones

and carbonates. J Chem Soc , Perkin Trans 2 485-489.

5 Le Questel JY, Laurence C, Lachkar A, Helbert M and Berthelot M (1992) Hydrogen-bond

basicity of secondary and tertiary amides, carbamates, ureas and lactams. J Chem Soc , Perkin

Trans 2 2091-2094.

6 Leo AJ (2000) Evaluating hydrogen-bond donor strength. J Pharm Sci 89: 1567-1578.

7 Schwöbel J, Ebert RU, Kühne R and Schüürmann G (2009) Prediction of the intrinsic

hydrogen bond acceptor strength of chemical substances from molecular structure. J Phys

Chem A 113: 10104-10112.

0,0 5,0 10,0 15,0 20,0 25,0 30,0 35,0 40,0 45,0

-100

0

125

250

375

500


min

1 - 25,025

WVL:214 nm


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