Synthesis, Structure and Conformation of Partially-Modified Retro- and Retro-Inversoψ[NHCH(CF3)]Gly Peptides

Copyright Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, 2003Chem. Eur. J. 2003

Supporting Information

for

Synthesis, Structure and Conformation of Partially-Modified Retro and

Retro-inverso ![NHCH(CF3)]Gly-Peptides

Alessandro Volonterio*, Stefano Bellosta, Fabio Bravin, Maria Cristina Bellucci, Luca

Bruché, Giorgio Colombo, Luciana Malpezzi, Stefania Mazzini, Stefano V. Meille,

Massimiliano Meli, Carmen Ramírez de Arellano, and Matteo Zanda*

Crystal Packing

The geometry of the intermolecular hydrogen bonds in 3a, 9a, and 9c is reported in Table 6.

The configuration of the nitrogen atom N(2) adapts both to optimize the local conformation

and the hydrogen bonding network. In 3a, the N–H···O bond makes infinite chains of

molecules parallel to the a axis (see below for a figure of the crystal packings). In the crystal

of compound 9c, the molecules are stacked along the c axis direction forming linear

supermolecular structures connected by N–H···O hydrogen bonds. Similar hydrogen bonding

systems, connecting

molecules in infinite linear structures along the a-axis, are present also in the crystal packing of 9a.

Weak C-H...F and C-H...O hydrogen bonds connect the linear supermolecular assemblies.

Table S1. Hydrogen-bonding geometry.

Donor-H...Acceptor d(D-H) (Å)

d(H...A) (Å)

d(D...A) (Å)

<(DHA) (°)

Symmetry operation for Acceptor

Compound 3a N(2)-H(01)...O(4) 0.83(2) 2.31(2) 3.111(3) 164(2) [x-1,y,z]C(2)-H(2A)...O(1) 0.97 2.62 3.312(3) 128.1 [x+1/2,-y+3/2,-z]C(2)-H(2A)...F(1) 0.97 2.58 3.405(3) 143.3 [x-1/2,-y+3/2,-z]C(9)-H(9)...F(1) 0.93 2.66 3.388(3) 135.5 [4 x-1,y-1,z]

Compound 9aN(1)-H(1N)...O(3) 0.76(4) 2.29(4) 3.013(4) 160(3) [x+1/2,-y+1/2,-z+1]N(2)-H(2N)...O(3) 0.85(3) 2.34(4) 3.137(3) 157(3) [x+1/2,-y+1/2,-z+1]C(9)-H(9)...F(1) 0.93 2.63 3.310(5) 130.2 [-x+1,y-1/2,-z+1/2]C(18)-H(18A)...F(1) 0.96 2.67 3.427(5) 136.0 [-x+2,y-1/2,-z+1/2]C(13)-H(13)...O(2) 0.98 2.66 3.515(4) 147.9 [x-1/2,-y+1/2,-z+1]C(4)-H(4A)...O(4) 0.96 2.56 3.411(5) 147.9 [x,y,z]

Compound 9cN(2)-H(2N)...O(3) 0.97(5) 2.39(5) 3.195(6) 141(4) [x,y,z+1]N(1)-H(1N)...O(3) 0.73(6) 2.99(6) 3.652(7) 152(6) [x,y,z+1]C(13)-H(13)...O(4) 0.98 2.48 3.345(7) 147 [x,y,z-1]C(15)-H(15)...O(4) 0.98 2.31 3.248(9) 158.9 [x,y,z-1]C(18)-H(18A)...O(2) 0.96 2.65 3.239(10) 120.0 [-y,x-y,z]

Figure 1S. Crystal packing of compound 3a showing the hydrogen bond interactions: N2-H1...O4#,

C2-H2A...O1', C2-H2A...F1" and C9-H9...F1*.

Figure 2S. Intermolecular hydrogen bonded assemblies in the crystals of compounds 9a and 9c.

(a) (b)

Ab initio calculations

Figure 3S. Starting geometries for the structures TI, and for the amides 15a-c.

Experimental

3a: Rf = 0.22 (Hexane/EtOAc 80:20); [α]23D = + 33.0 (c = 0.7, CHCl3); mp: 71-72 °C; FTIR

(KBr): νmax = 3449, 1800, 1702, 1277, 1109 cm-1; 1H NMR (250 MHz, CDCl3): δ = 7.35-7.21 (m,

5H), 4.74 (m, 1H), 4.28 (m, 1H), 4.18 (dd, J = 9.0, 2.7 Hz, 1H), 3.70 (m, 1H), 3.63 (s, 3H), 3.64 (q,

J = 6.9 Hz, 1H), 3.45 (dd, J = 14.9, 3.9 Hz, 1H), 3.35 (dd, J = 13.5, 3.0 Hz, 1H), 3.10 (dd, J = 14.9,

9.6 Hz, 1H), 2.80 (dd, J = 13.5, 9.6 Hz, 1H), 1.32 (d, J = 6,9 Hz, 3H); 19F NMR (250 MHz, CDCl3):

δ = - 77.8 (d, J = 7.1 Hz); 13C (250 MHz, CDCl3): δ = 175.9, 169.3, 153.6, 135.7, 129.4, 129.0,

127.4, 126.1 (q, J = 282.5 Hz), 66.6, 55.9, 55.5, 55.1 (q, J = 29.4 Hz), 51.9, 37.9, 36.2, 19.5; MS

(70 eV): e/z (%): 402 (9) [M+], 370 (7), 343 (100).

15a

15b 15c

TI

4a: Rf = 0.12 (Hexane/EtOAc 80:20); 1H NMR (250 MHz, CDCl3): δ = 7.39-7.18 (m, 5H),

4.70 (m, 1H), 4.21 (m, 2H), 3.91 (m, 1H), 3.72 (s, 3H), 3.62 (q, J = 7.0 Hz, 1H), 3.37 (dd, J = 17.0,

9.6 Hz, 1H), 3.32 (dd, J = 13.5, 3.5 Hz, 1H), 3.13 (dd, J = 17.0, 3.5 Hz, 1H), 2.80 (dd, J = 13.5, 9.6

Hz, 1H), 1.32 (d, J = 7,0 Hz, 3H); 19F NMR (250 MHz, CDCl3): δ = - 75.9 (d, J = 7.1 Hz).

3b: Rf = 0.51 (Hexane/EtOAc 70:30); [α]23D = + 45.6 (c = 0.7, CHCl3); mp: 60-61 °C; FTIR

(KBr): νmax = 3342, 1798, 1724, 1707, 1277, 1221 cm-1; 1H NMR (250 MHz, CDCl3): δ = 4.50 (m,

1H), 4.38 (t, J = 8.5 Hz, 1H), 4.24 (dd, J = 8.5, 2.7 Hz, 1H), 3.69 (s, 3H), 3.64 (m, 1H), 3.63 (q, J =

6.9 Hz), 3.50 (dd, J = 14.7, 3.9 Hz, 1H), 3.01 (dd, J = 14.7, 10.0 Hz, 1H), 2.39 (m, 1H), 2.00 (br s,

1H), 1.30 (d, J = 6.9 Hz, 3H), 0.94 (d, J = 6.9 Hz, 3H), 0.91 (6.9 Hz, 3H); 19F NMR (250 MHz,

CDCl3): δ = - 77.6 (d, J = 7.2 Hz); 13C (250 MHz, CDCl3): δ = 175.8, 169.2, 154.3, 126.0 (q, J =

283.0 Hz), 63.7, 58.8, 55.6, 54.9 (q, J = 29.6 Hz), 51.9, 35.9, 28.4, 19.3, 18.0, 14.7; MS (70 eV): e/z

(%): 355 (44) [M++1], 295 (100).

4b: Rf = 0.38 (Hexane/EtOAc 70:30); 1H NMR (250 MHz, CDCl3): δ = 4.46 (m, 1H), 4.33 (m,

1H), 4.24 (dd, J = 8.8, 3.1 Hz, 1H), 3.91 (m, 1H), 3.73 (s, 3H), 3.61 (q, J = 6.9 Hz), 3.41 (dd, J =

17.0, 9.6 Hz, 1H), 3.14 (dd, J = 17.0, 3.5 Hz, 1H), 2.47 (br s, 1H), 2.37 (m, 1H), 1.33 (d, J = 6.9 Hz,

3H), 0.93 (d, J = 6.9 Hz, 3H), 0.88 (6.9 Hz, 3H); 19F NMR (250 MHz, CDCl3): δ = - 75.7 (d, J = 7.3

Hz).

3d: Rf = 0.34 (Hexane/Et2O 60:40); [α]23D = +37.3 (c = 1.0, CHCl3); mp: 83-84 °C; 1H NMR

(500 MHz, CDCl3): δ = 7.39-7.31 (m, 5H), 5.15 (d, J = 12.4 Hz, 1H), 5.07 (d, J = 12.4 Hz, 1H),

4.45 (m, 1H), 4.32 (m, 1H), 4.21 (dd, J = 8.7, 2.7 Hz, 1H), 3.58 (m, 1H), 3.45 (dd, J = 15.1, 4.1 Hz,

1H), 3.37 (d, J = 5.0 Hz, 1H), 3.04 (dd, J = 15.1, 9.2 Hz, 1H), 2.38 (m, 1H), 1.99 (m, 1H), 1.81 (br

s, 1H), 0.95 (d, J = 6.9 Hz, 3H), 0.92 (d, J = 6.9 Hz, 3H), 0.89 (d, J = 6.9 Hz, 3H), 0.83 (d, J = 6.9

Hz, 3H); 19F NMR (500 MHz, CDCl3): δ = - 76.7 (d, J = 6.9 Hz); 13C (500 MHz, CDCl3): δ =

174.9, 169.2, 154.2, 135.6, 128.6, 128.4, 128.1, 126.0 (q, J = 282.2 Hz), 66.5, 66.4, 63.7, 58.8, 55.4

(q, J = 29.3 Hz), 36.3, 31.7, 28.4, 19.3, 18.0, 17.4, 14.7; MS (70 eV): e/z (%): 460 (5) [M++1], 323

(100), 91 (40).

4d: Rf = 0.25 (Hexane/Et2O 60:40); 19F NMR (500 MHz, CDCl3): δ = - 75.5 (d, J = 6.7 Hz).

3e: Rf = 0.38 (Hexane/EtOAc 50:50); [α]23D = − 2.5 (c = 0.5, CHCl3); mp: 86-87 °C; 1H NMR


4.41 (m, 2H), 4.00 (m, 2H), 3.60 (q, J = 6.6 Hz, 1H), 3.34 (d, J = 5.0 Hz, 1H), 3.26 (d, J = 6.6 Hz,

2H), 1.99 (m, 1H), 1.86 (br s, 1H), 0.95 (d, J = 6,6 Hz, 3H), 0.84 (d, J = 6,6 Hz, 3H); 19F NMR (250

MHz, CDCl3): δ = - 77.8 (d, J = 6.9 Hz); 13C (250 MHz, CDCl3): δ = 175.1, 169.7, 153.7, 135.7,

128.6, 128.4, 128.2, 126.0 (q, J = 282.3 Hz), 66.8, 66.6, 62.3, 56.2 (q, J = 29.4 Hz), 35.6, 31.8,

19.3, 17.5; MS (70 eV): e/z (%): 417 (9) [M++1], 281 (100), 91 (29).

4e: Rf = 0.38 (Hexane/EtOAc 50:50); 19F NMR (250 MHz, CDCl3): δ = - 76.0 (d, J = 7.2 Hz).

3f: Rf = 0,32 (Hexane/EtOAc 80:20); [α]23D = + 19.0 (c = 0.2, CHCl3); mp: 95-96 °C; 1H

NMR (250 MHz, CDCl3): δ = 7.40-7.16 (m, 15H), 5.07 (d, J = 12.0 Hz, 1H), 5.00 (d, J = 12.0 Hz,

1H), 4.63 (m, 1H), 4.22 (m, 1H), 4.14 (dd, J = 9.0, 3.0 Hz, 1H), 3.90 (t, J = 6.5 Hz, 1H), 3.69 (m,

1H), 3.34 (m, 2H), 3.10 (dd, J = 15.5, 10.0 Hz, 1H), 2.96 (m, 2H), 2.69 (dd, J = 13.5, 10.0 Hz, 1H);

19F NMR (250 MHz, CDCl3): δ = - 77.3 (d, J = 6.8 Hz); 13C (250 MHz, CDCl3): δ = 174.0, 169.1,

153.6, 136.4, 135.4, 135.3, 129.5, 129.3, 129.0, 128.6, 128.45, 128.40, 128.3, 127.4, 126.9, 126.0

(q, J = 283.0 Hz), 66.8, 66.5, 61.7, 55.5, 55.2 (q, J = 29.4 Hz), 39.9, 37.9, 36.3; MS (70 eV): e/z

(%): 555 (5) [M++1], 463 (100), 419 (80), 91 (9).

4f: Rf = 0,30 (Hexane/EtOAc 80:20); 19F NMR (250 MHz, CDCl3): δ = - 75.9 (d, J = 7.6 Hz).

3g: Rf = 0.36 (hexane/Et2O 70:30); 1H NMR (250 MHz, CDCl3): δ = 7.39-7.18 (m, 10H), 4.67

(m, 1H), 4.25 (m, 1H), 4.16 (dd, J = 8.8, 3.2 Hz, 1H), 3.74 (m, 1H), 3.66 (m, 1H), 3.45 (dd, J =

15.3, 4.0 Hz, 1H), 3.34 (dd, J = 13.7, 3.2 Hz, 1H), 3.04 (dd, J = 15.3, 9.6 Hz, 1H), 2.92 (m, 2H),

2.75 (dd, J = 13.7, 10.4 Hz, 1H), 2.15 (br s, 1H), 1.33 (s, 9H); 19F NMR (250 MHz, CDCl3): δ = -

76.9 (d, J = 6.6 Hz); 13C (250 MHz, CDCl3): δ = 173.1, 169.1, 153.6, 136.6, 135.3, 129.5, 129.0,

128.3, 127.4, 126.8, 125.9 (q, J = 281.4 Hz), 81.8, 66.5, 61.7, 55.4, 54.9 (q, J = 29.6 Hz), 39.7,

37.8, 36.0, 27.9.

4g: Rf = 0.30 (hexane/Et2O 70:30); 19F NMR (250 MHz, CDCl3): δ = - 75.0 (d, J = 7.0 Hz).

3h: Rf = 0.36 (Hexane/EtOAc 80:20); [α]23D = +18.4 (c = 0.8, CHCl3); mp: 72-73 °C; 1H

NMR (250 MHz, CDCl3): δ = 7.40-7.20 (m, 10H), 5.12 (d, J = 12.5 Hz, 1H), 5.06 (d, J = 12.5 Hz,

1H), 4.73 (m, 1H), 4.26 (m, 1H), 4.16 (dd, J = 8.9, 3.1 Hz, 1H), 3.62 (m, 2H), 3.51 (dd, J = 15.1,

3.9 Hz, 1H), 3.36 (dd, J = 13.5, 3.1 Hz, 1H), 3.08 (dd, J = 15.1, 10.0 Hz, 1H), 2.78 ( dd, J = 13.5,

10.0 Hz), 2.10 (br s, 1H), 1.81 (m, 1H), 1.46 (m, 2H), 0.91 (d, J = 3.1 Hz, 3H), 0.88 (d, J = 3.1 Hz,

3H); 19F NMR (250 MHz, CDCl3): δ = - 77.5 (d, J = 6.9 Hz, 3F); 13C (250 MHz, CDCl3): δ = 175.8,

169.3, 153.6, 135.6, 135.4, 129.3, 129.0, 128.6, 128.3, 128.0, 127.4, 126.1 (q, J = 176.4 Hz), 66.7,

66.6, 59.4, 55.5, 55.4 (q, J = 18.3 Hz), 42.9, 37.9, 36.3, 24.7, 23.0, 21.6; MS (70 eV): e/z (%): 521

(8) [M++1], 385 (100), 91 (34).

4h: Rf = 0.26 (Hexane/EtOAc 80:20); 1H NMR (250 MHz, CDCl3): δ = 7.40-7.18 (m, 10H),

5.17 (d, J = 12.0 Hz, 1H), 5.10 (d, J = 12.5 Hz, 1H), 4.66 (m, 1H), 4.19 (m, 2H), 3.87 (m, 1H), 3.45

(dd, J = 17.0, 8.5 Hz, 1H), 3.30 (dd, J = 13.5, 3.1 Hz, 1H), 3.06 (dd, J = 17.0, 3.9 Hz, 1H), 2.76 (dd,

J = 13.5, 9.7 Hz), 1.92 (br s, 1H), 1.69 (m, 1H), 1.42 (m, 2H), 0.88 (d, J = 6.6 Hz, 6H); 19F NMR

(250 MHz, CDCl3): δ = - 75.9 (d, J = 7.0 Hz).

3i: Rf = 0.33 (Hexane/Et2O 60:40); [α]23D = + 29.2 (c = 1.0, CHCl3); FTIR (film): νmax 2962,

1784, 1732, 1699, 1388, 1162 cm-1; 1H NMR (500 MHz, CDCl3): δ = 7.39-7.30 (m, 5H), 5.12 (d, J

= 12.4 Hz, 1H), 5.08 (d, J = 12.4 Hz, 1H), 4.48 (m, 1H), 4.33 (m, 1H), 4.21 (dd, J = 9.2, 2.7 Hz,

1H), 3.59 (m, 2H), 3.51 (dd, J = 14.7, 3.7 Hz, 1H), 2.98 (dd, J = 14.7, 10.1 Hz, 1H), 2.39 (m, 1H),

1.80 (m, 1H), 1.67 (m, 1H), 1.42 (m, 2H), 0.90 (m, 12H); 19F NMR (500 MHz, CDCl3): δ = - 76.8

(d, J = 6.3 Hz); 13C (500 MHz, CDCl3): δ = 175.8, 169.2, 154.3, 135.6, 128.6, 128.4, 128.0, 126.1

(q, J = 282.6 Hz), 66.6, 63.7, 59.2, 58.9, 55.1 (q, J = 29.4 Hz), 42.8, 36.1, 28.5, 24.6, 23.0, 21.5,

18.0, 14.7; MS (70 eV): e/z (%): 475 (2) [M++1], 337 (100), 281 (27), 91 (30).

4i: Rf = 0.24 (Hexane/Et2O 60:40); 1H NMR (250 MHz, CDCl3): δ = 7.35 (m, 5H), 5.15 (d, J

= 12.0 Hz, 1H), 5.09 (d, J = 12.0 Hz, 1H), 4.42 (m, 1H), 4.25 (m, 2H), 3.82 (m, 1H), 3.45 (m, 2H),

3.04 (dd, J = 17.0, 3.9 Hz, 1H), 2.36 (m, 1H), 1.88 (br s, 1H), 1.67 (m, 1H), 1.40 (m, 2H), 0.89 (m,

12H); 19F NMR (250 MHz, CDCl3): δ = - 75.9 (d, J = 8.1 Hz).

3j: Rf = 0.27 (hexane/EtOAc 80:20); [α]23D = + 3.3 (c = 0.3, CHCl3); FTIR (film): νmax 2954,

1784, 1741, 1704, 1392, 1168, 1111 cm-1; 1H NMR (250 MHz, CDCl3): δ = 7.38-7.17 (m, 10H),

5.16 (d, J = 12.4 Hz, 1H), 5.06 (d, J = 12.4 Hz, 1H), 4.71 (m, 1H), 4.35 (m, 1H), 4.26 (m, 1H), 4.16

(dd, J = 8.1, 3.5 Hz, 1H), 3.55 (dd, J = 17.8, 9.3 Hz, 1H), 3.30 (dd, J = 13.5, 3.1 Hz, 1H), 3.25 (m,

1H), 3.08 (dd, J = 17.8, 3.9 Hz, 1H), 3.00 (m, 1H), 2.75 (dd, J = 13.5, 9.6 Hz, 1H), 1.92 (m, 4H);


153.5, 135.8, 135.1, 129.4, 128.9, 128.5, 128.1, 127.4, 126.4 (q, J = 190.5 Hz), 66.6, 66.4, 60.9,

57.0 (q, J = 27.7 Hz), 50.2, 37.8, 32.3, 30.3, 24.2; MS (70 eV): e/z (%): 505 (2) [M++1], 369 (100),

91 (12).

4j: Rf = 0.21 (hexane/EtOAc 80:20); 1H NMR (250 MHz, CDCl3): δ = 7.41-7.16 (m, 10H),

5.11 (d, J = 12.4 Hz, 1H), 5.03 (d, J = 12.4 Hz, 1H), 4.68 (m, 1H), 4.39-4.10 (m, 3H), 3.89 (dd, J =

8.9, 3.9 Hz, 1H), 3.47 (dd, J = 14.3, 4.6 Hz, 1H), 3.31 (m, 1H), 3.25 (dd, J = 14.3, 10.4 Hz, 1H),

2.91 (m, 1H), 2.81 (dd, J = 13.1, 9.3 Hz, 1H), 2.12 (m, 1H),1.92 (m, 4H); 19F NMR (250 MHz,

CDCl3): δ = - 70.8 (d, J = 6.3 Hz);

3k: Rf = 0.15 (Hexane/EtOAc 80:20); [α]23D = + 40.9 (c = 0.3, CHCl3); FTIR (film): νmax

2984, 1785, 1741, 1702, 1394, 1213, 1162 cm-1; 1H NMR (250 MHz, CDCl3): δ = 7.39-7.17 (m,

5H), 4.70 (m, 1H), 4.18 (m, 4H), 3.82 (m, 1H), 3.67 (d, J = 17.6 Hz, 1H), 3.55 (d, J = 17.6 Hz 1H),

3.30 (m, 3H), 2.78 (dd, J = 12.9, 9.2 Hz, 1H), 2.12 (br s, 1H), 1.27 (t, J = 7.4 Hz); 19F NMR (250

MHz, CDCl3): δ = - 76.3 (d, J = 7.2 Hz, 3F); 13C (250 MHz, CDCl3): δ = 171.3, 169.3, 153.5,

135.1, 129.4, 129.0, 127.4, 126.0 (q, J = 283.0 Hz), 66.5, 61.2, 55.9 (q, J = 29.6 Hz), 55.4, 49.2,

37.8, 35.6, 14.1; MS (70 eV): e/z (%): 464 (2) [M++1], 403 (100), 329 (63), 178 (40).

4k: Rf = 0.10 (Hexane/EtOAc 80:20); 1H NMR (250 MHz, CDCl3): δ = 7.39-7.19 (m, 5H),

4.72 (m, 1H), 4.20 (m, 4H), 3.83 (m, 1H), 3.63 (m, 2H), 3.34 (m, 3H), 2.81 (dd, J = 13.1, 9.6 Hz,

1H), 2.65 (br s, 1H), 1.25 (t, J = 7.0 Hz); 19F NMR (250 MHz, CDCl3): δ = - 76.2 (d, J = 6.9 Hz).

3l: Rf = 0.41 (iPr2O/Hexane 60:40); FTIR (film): νmax = 1789, 1740, 1702, 1200 cm-1; 1H

NMR (500 MHz, CDCl3): δ = 7.38-7.22 (m, 10H), 4.70 (m, 1H), 4.24 (m, 1H), 4.17 (m, 2H), 4.10

(d, J = 13.6 Hz, 1H), 4.06 (q, J = 7.0 Hz, 2H), 3.93 (d, J = 13.6 Hz, 1H), 3.58 (dd, J = 15.8, 9.2 Hz,

1H), 3.55 (d, J = 17.6 Hz, 1H), 3.46 (d, J = 17.6 Hz, 1H), 3.44 (dd, J = 13.6, 3.3 Hz, 1H), 3.27 (dd,

J = 15.8, 4.4 Hz, 1H), 2.81 (dd, J = 13.6, 9.9 Hz, 1H), 1.19 (t, J = 7.0 Hz, 3H); 19F NMR (235.4

MHz, CDCl3): δ = -71.4 (d, J = 7.0 MHz); 13C NMR (127.7 MHz, CDCl3): δ = 171.4, 169.1, 153.6,

138.0, 135.6, 129.5, 129.04, 129.01, 128.3, 127.4, 127.3, 126.8 (q, J = 288.4 Hz), 66.4, 60.5, 58.4

(q, J = 27.7 Hz), 55.6, 55.4, 51.6, 37.8, 33.7, 14.1; MS (70 eV): e/z (%): 492 (2) [M++1], 419 (18),

192 (40), 91 (100).

3m: Rf = 0.50 (Hexane/EtOAc 70:30); FTIR (film): νmax = 3351, 1795, 1703, 1265 cm-1; 1H

NMR (500 MHz, CDCl3): δ = 7.40-7.28 (m, 5H), 5.13 (s, 2H), 4.41 (m, 2H), 4.01 (m, 2H), 3.73 (m,

1H), 3.67 (d, J = 18.0 Hz, 1H), 3.57 (d, J = 18.0 Hz , 1H), 3.26 (m, 2H), 1.97 (br s, 1H); 19F NMR

(235.4 MHz, CDCl3): δ = -76.7 (d, J = 6.8 Hz); 13C NMR (127.7 MHz, CDCl3): δ = 171.9, 169.5,

153.6, 135.4, 128.6, 128.4, 128.3, 126.1 (q, J = 283.0 Hz), 66.7, 62.3, 55.9 (q, J = 27.7 Hz), 49.4,

42.5, 35.4; MS (70 eV): e/z (%): 374 (45) [M++1], 91 (100).

5a: Rf = 0.39 (Hexane/EtOAc 70:30); 1H NMR (250 MHz, CDCl3): δ = 7.40-7.21 (m, 5H),

4.71 (m, 1H), 4.21 (m, 2H), 3.92 (m, 1H), 3.74 (s, 3H), 3.64 (q, J = 6.9 Hz, 1H), 3.56 (dd, J = 17.0,

9.7 Hz, 1H), 3.30 (dd, J = 13.5, 3.1 Hz, 1H), 3.05 (dd, J = 17.0, 3.8 Hz, 1H), 2.81 (dd, J = 13.5, 9.6

Hz, 1H), 2.05 (br s, 1H), 1.35 (d, J = 6,9 Hz, 3H); 19F NMR (250 MHz, CDCl3): δ = - 75.8 (d, J =

7.1 Hz).

5b: Rf = 0.32 (Hexane/EtOAc 70:30); [α]23D = + 45.6 (c = 0.6, CHCl3); mp: 91-92 °C; FTIR

(KBr): νmax = 3449, 1794, 1741, 1670, 1275, 1156 cm-1; 1H NMR (250 MHz, CDCl3): δ = 7.39-

7.18 (m, 5H), 4.70 (m, 1H), 4.26 (m, 1H), 4.19 (dd, J = 9.0, 3.0 Hz, 1H), 3.76 (m, 1H), 3.71 (s, 3H),

3.63 (q, J = 7.2 Hz, 1H), 3.35 (m, 3H), 3.22 (dd, J = 15.8, 4.1 Hz, 1H), 1.98 (br s, 1H), 1.31 (d, J =

7,2 Hz, 3H); 19F NMR (250 MHz, CDCl3): δ = - 77.4 (d, J = 7.2 Hz); 13C (250 MHz, CDCl3): δ =

175.5, 169.5, 153.6, 135.3, 129.4, 129.0, 127.4, 126.0, (q, J = 283.0 Hz), 66.5, 55.8, 55.46, 55.45

(q, J = 29.6 Hz), 52.0, 37.7, 36.0, 19.6; MS (70 eV): e/z (%): 403 (52) [M++1], 370 (3), 343 (100).

7a: Rf = 0.34 (Hexane/EtOAc 60:40); [α]23D = − 40.6 (c = 0.9, CHCl3); m.p. 102-103 °C;

FTIR (film): νmax = 1795, 1746, 1700, 1650 cm-1; 1H NMR (500 MHz, CDCl3): δ = 7.79 (br d, J =

7.3 Hz, 1H), 7.25 (m, 10H), 4.68 (m, 1H), 4.60 (m, 1H), 4.23 (m, 1H), 4.17 (m, 1H), 3.91 (m, 2H),

3.69 (s, 3H), 3.26 (m, 2H), 3.15 (m, 2H), 2.87 (dd, J = 13.7, 8.7 Hz, 1H), 2.75 (m, 1H), 1.72 (m,

1H), 1.44 (d, J = 6.9 Hz, 3H); 19F NMR (500 MHz, CDCl3): δ = - 73.6 (d, J = 5.9 Hz); 13C (500

MHz, CDCl3): δ = 173.3, 172.7, 169.7, 153.3, 136.4, 134.9, 129.3, 129.2, 129.0, 128.7, 127.5, 126.1

(q, J = 286.7 Hz), 66.5, 60.7, 55.2, 54.0 (q, J = 27.7 Hz), 52.2, 47.8, 39.6, 37.7, 36.3, 17.4; MSCI:

e/z (%): 550 (100) [M++1].

8a: Rf = 0.24 (Hexane/EtOAc 60:40); [α]23D = + 1.9 (c = 1.6, CHCl3); m.p. 83-84 °C; FTIR

(film): νmax = 1800, 1731, 1685 cm-1; 1H NMR (400 MHz, CDCl3): δ = 7.49 (br d, J = 7.6 Hz, 1H),

7.36-7.14 (m, 10H), 4.58 (m, 2H), 4.21 (m, 1H), 4.15 (dd, J = 9.1, 2.9 Hz, 1H), 3.82 (m, 1H), 3.73

(s, 3H), 3.59 (dd, J = 8.5, 4.1 Hz, 1H), 3.21 (m, 2H), 3.12 (dd, J = 17.9, 4.7 Hz, 1H), 2.86 (m, 2H),

2.68 (dd, J = 13.5, 9.7 Hz, 1H), 1.70 (br s, 1H), 1.38 (d, J = 7.3 Hz, 3H); 19F NMR (250 MHz,

CDCl3): δ = - 76.3 (d, J = 7.6 Hz); 13C (250 MHz, CDCl3): δ = 172.9, 172.5, 168.9, 153.1, 136.9,

134.9, 129.3, 129.2, 129.0, 128.8, 127.4, 127.2, 125.7 (q, J = 281.1 Hz), 66.4, 61.5, 54.9 (q, J =

29.6 Hz), 54.7, 52.3, 47.8, 39.3, 37.6, 29.6, 18.0; MSCI: e/z (%): 550 (100) [M++1].

7b: Rf = 0.50 (Hexane/EtOAc 60:40); [α]23D = − 1.8 (c = 1.1, CHCl3); m.p. 105 °C; FTIR

(film): νmax = 1770, 1760, 1747, 1704, 1651 cm-1; 1H NMR (500 MHz, CDCl3): δ = 7.58 (br d, J =

6.9 Hz, 1H), 7.31 (m, 3H), 7.20 (m, 2H), 4.72 (m, 1H), 4.59 (m, 1H), 4.28 (m, 1H), 4.20 (m, 1H),

3.88 (m, 1H), 3.71 (s, 3H), 3.44 (m, 1H), 3.33 (m, 3H), 2.81 (dd, J = 13.3, 9.6 Hz, 1H), 2.09 (m,

1H), 1.79 (br s, 1H), 1.48 (d, J = 7.3 Hz, 3H), 1.02 (d, J = 6.4 Hz, 3H), 0.92 (d, J = 6.4 Hz, 3H); 19F

NMR (500 MHz, CDCl3): δ = - 73.6 (d, J = 5.8 Hz); 13C (500 MHz, CDCl3): δ = 173.4, 172.7,

169.7, 153.4, 134.9, 129.3, 129.0, 127.6, 126.3 (q, J = 285.7 Hz), 66.4, 65.4, 55.3, 54.0 (q, J = 27.4

Hz), 52.2, 47.7, 37.7, 36.3, 31.6, 19.2, 17.6, 17.4; MSCI: e/z (%): 502 (100) [M++1].

8b: Rf = 0.37 (Hexane/AcOEt 60:40); [α]23D = + 2.2 (c = 1.2, CHCl3); FTIR (film): νmax =

1783, 1741, 1695, 1682 cm-1; 1H NMR (250 MHz, CDCl3): δ = 7.33 (m, 4H), 7.20 (m, 2H), 4.69

(m, 1H), 4.59 (m, 1H), 3.84 (m, 1H), 3.75 (s, 3H), 3.42 (dd, J = 17.7, 4.8 Hz, 1H), 3.23 (m, 3H),

2.76 (dd, J = 12.8, 9.6 Hz, 1H), 2.14 (m, 1H), 1.92 (br s, 1H), 1.42 (d, J = 7.2 Hz, 3H), 1.00 (d, J =

6.4 Hz, 3H), 0.91 (d, J = 6.4 Hz, 3H); 19F NMR (250 MHz, CDCl3): δ = - 76.2 (d, J = 7.1 Hz); 13C

(250 MHz, CDCl3): δ = 173.0, 172.3, 169.3, 153.3, 134.9, 129.3, 129.0, 127.5, 125.7 (q, J = 283.0

Hz), 66.4, 65.6, 55.5 (q, J = 29.6 Hz), 55.3, 52.4, 47.9, 37.7, 31.9, 29.7, 19.7, 18.2, 17.5; MSCI: e/z

(%): 502 (10) [M++1], 279 (100).

7c: Rf = 0.47 (Hexane/EtOAc 60:40); [α]23D = − 2.1 (c = 0.7, CHCl3); FTIR (film): νmax =

3357, 1801, 1744, 1692, 1632, 1167cm-1; 1H NMR (500 MHz, CDCl3): δ = 7.44 (br d, J = 7.3, 1H),

7.31 (m, 3H), 7.21 (m, 2H), 4.70 (m, 1H), 4.64 (m, 1H), 4.26 (m, 1H), 4.22 (m, 1H), 3.73 (m, 1H),

3.60 (s, 3H), 3.44 (m, 1H), 3.36 (m, 3H), 2.80 (dd, J = 12.8, 10.4 Hz, 1H), 2.15 (m, 1H), 1.78 (br s,

1H), 1.52 (d, J = 7.3 Hz, 3H), 1.02 (d, J = 6.7 Hz, 3H), 0.93 (d, J = 6.7 Hz, 3H); 19F NMR (500

MHz, CDCl3): δ = - 73.6 (d, J = 6.4 Hz); 13C (500 MHz, CDCl3): δ = 173.2, 172.4, 169.6, 153.4,

135.1, 129.4, 129.3, 129.0, 127.5, 126.3 (q, J = 286.7 Hz), 66.5, 65.1, 55.4, 54.3 (q, J = 27.7 Hz),

52.1, 47.7, 37.7, 31.8, 19.3, 17.9, 17.2; MSCI: e/z (%): 502 (100) [M++1].

8c: Rf = 0.22 (Hexane/EtOAc 60:40); [α]23D = + 11.9 (c = 0.8, CHCl3); m.p. 89-90 °C; FTIR

(film): νmax = 3341, 1803, 1761, 1743, 1695, 1639, 1155 cm-1; 1H NMR (250 MHz, CDCl3): δ =

7.39 (br d, J = 7.9, 1H), 7.27 (m, 3H), 7.15 (m, 2H), 4.64 (m, 1H), 4.56 (m, 1H), 4.18 (m, 2H), 3.69

(s, 3H), 3.64 (m, 1H), 3.41 (dd, J = 17.7, 4.9 Hz, 1H), 3.25 (dd, J = 13.8, 2.9 Hz, 1H), 3.14 (m, 1H),

3.09 (d, J = 3.9 Hz, 1H), 2.70 (dd, J = 13.8, 9.8 Hz, 1H), 2.15 (m, 1H), 1.78 (br s, 1H), 1.37 (d, J =

7.9 Hz, 3H), 0.97 (d, J = 6.9 Hz, 3H), 0.88 (d, J = 6.9 Hz, 3H); 19F NMR (250 MHz, CDCl3): δ = -

76.2 (d, J = 7.6 Hz, 3F); 13C (250 MHz, CDCl3): δ = 173.3, 172.2, 169.3, 153.3, 134.8, 129.3,

129.1, 127.5, 125.7 (q, J = 281.1 Hz), 66.5, 56.1, (q, J = 29.6 Hz), 55.3, 52.3, 47.5, 37.7, 34.9, 31.9,

29.7, 19.5, 17.9, 17.2; MSCI: e/z (%): 502 (100) [M++1].

9b: Rf = 0.35 (hexane/EtOAc 70:30); [α]23D = − 15.1 (c = 0.7, CHCl3); mp: 48-49 °C; FTIR

(KBr): νmax = 3335, 1742, 1657, 1167 cm-1; 1H NMR (250 MHz, CDCl3): δ = 7.35 (m, 5H), 7.23

(br d, J = 6.4 Hz, 1H), 5.15 (s, 2H), 4.60 (q, J = 7.2 Hz, 1H), 3.74 (s, 3H), 3.67 (q, J = 7.2 Hz, 1H),

3.54 (m, 1H), 2.64 (dd, J = 15.4, 3.4 Hz, 1H), 2.40 (dd, J = 15.4, 9.4 Hz, 1H), 2.02 (br s, 1H), 1.78

(m, 1H), 1.5 (m, 2H), 1.44 (d, J = 7.2 Hz, 3H), 0.91 (d, J = 4.1 Hz, 3H), 0.88 (d, J = 4.1 Hz, 3H);


168.2, 135.5, 128.6, 128.4, 128.2, 126.0 (q, J = 282.2 Hz), 66.8, 58.4, 55.3 (q, J = 27.7 Hz), 52.4,

48.2, 42.9, 35.9, 24.6, 22.9, 21.6, 17.9; MS (70 eV): e/z (%): 447 (7) [M++1], 311 (93), 208 (30),

166 (30), 91 (100).

9c: Rf = 0.37 (Hexane/EtOAc 70:30); [α]23D = + 18.1 (c = 0.6, CHCl3); FTIR (KBr): νmax =

3405, 1736, 1649, 1161 cm-1; 1H NMR (500 MHz, CDCl3): δ = 7.36-7.19 (m, 8H), 7.02 (m, 3H),

5.16 (d, J = 12.2 Hz, 1H), 5.12 (d, J = 12.2 Hz, 1H), 4.94 (m, 1H), 3.70 (s, 3H), 3.54 (m, 1H), 3.50

(q, J = 7.0 Hz, 1H), 3.10 (d, J = 6.0 Hz, 2H), 2.55 (dd, J = 15.5, 3.0 Hz, 1H), 2.30 (dd, J = 15.5,

10.0 Hz, 1H), 2.28 (br s, 1H), 1.14 (d, J = 7.0 Hz, 3H); 19F NMR (250 MHz, CDCl3): δ = - 76.2 (d,

J = 6.4 Hz); 13C (250 MHz, CDCl3): δ = 174.8, 171.3, 168.7, 135.7, 135.0, 129.3, 128.6, 128.1,

127.1, 125.9 (q, J = 283.0 Hz), 67.3, 55.5 (q, J = 29.6 Hz), 54.8, 53.2, 52.2, 37.7, 35.9, 19.1; MS

(70 eV): e/z (%): 481 (100) [M++1], 421 (37), 91 (44).

9d: Rf = 0.29 (Hexane/EtOAc 70:30); [α]23D = − 50.2 (c = 0.4, CHCl3); FTIR (film): νmax =

1741, 1648, 1450, 1272, 1168 cm-1; 1H NMR (500 MHz, CDCl3): δ = 7.38-7.30 (m, 5H), 5.18 (d, J

= 12.8 Hz, 1H), 5.15 (d, J = 12.8 Hz, 1H), 4.58 (dd, J = 8.3, 3.4 Hz, 1H), 3.73 (m, 3H), 3.70 (s, 3H),

3.62 (q, J = 6.8 Hz, 1H), 2.75 (dd, J = 15.5, 4.1 Hz, 1H), 2.56 (dd, J = 15.5, 8.7 Hz, 1H), 2.54 (br s,

1H), 2.20 (m, 1H), 2.05 (m, 1H), 1.99 (m, 2H), 1.32 (d, J = 6.8 Hz, 3H); 19F NMR (250 MHz,

CDCl3): δ = - 70.0 (d, J = 7.1 Hz); 13C (250 MHz, CDCl3): δ = 175.0, 171.7, 167.7, 135.7, 128.7,

128.2, 128.0, 126.0 (q, J = 281.1 Hz), 66.7, 58.9, 55.4, 55.0 (q, J = 29.6 Hz), 51.9, 47.2, 34.6, 29.1,

24.6, 19.3; MS (70 eV): e/z (%): 431 (100) [M++1].

9e: Rf = 0.68 (hexane/EtOAc 70:30); [α]23D = + 12.1 (c = 0.7, CHCl3); mp: 73-74 °C; FTIR

(KBr): νmax = 3340, 1736, 1729, 1660, 1171 cm-1; 1H NMR (250 MHz, CDCl3): δ = 7.40-7.19 (m,

12H), 7.08 (m, 3H), 6.70 (br d, J = 7.7 Hz, 1H), 5.18 (d, J = 12.0 Hz, 1H), 5.15 (d, J = 12.0 Hz,

1H), 5.10 (d, J = 12.0 Hz, 1H), 5.09 (d, J = 12.0 Hz, 1H), 4.93 (m, 1H), 3.50 (m, 1H), 3.38 (d, J =

5.0 Hz, 1H), 3.14 (d, J = 6.2 Hz, 2H), 2.60 (dd, J = 15.8, 3.9 Hz, 1H), 2.35 (dd, J = 15.8, 8.9 Hz,

1H), 1.99 (m, 1H), 1.84 (br s, 1H), 0.94 (d, J = 12.0 Hz, 1H), 0.86 (d, J = 12.0 Hz, 1H); 19F NMR

(250 MHz, CDCl3): δ = - 76.5 (d, J = 7.0 Hz); 13C (250 MHz, CDCl3): δ = 174.6, 171.4, 168.2,

135.9, 135.5, 135.1, 129.3, 128.6, 128.4, 127.1, 126.0 (q, J = 283.0 Hz), 67.2, 66.8, 65.9, 56.0 (q, J

= 27.7 Hz), 53.4, 37.7, 36.2, 31.9, 19.1, 17.6; MS (70 eV): e/z (%): 585 (100) [M++1], 91 (37).

10: Rf = 0.22 (Hexane/EtOAc 50:50); [α]23D = − 70.4 (c = 0.4, CHCl3); FTIR (film): νmax =

1741, 1659, 1216 cm-1; 1H NMR (500 MHz, CDCl3): δ = 8.01 (br d, J = 7.9 Hz, 1H), 7.38-7.16 (m,

10H), 6.36 (br d, J = 8.5 Hz, 1H), 5.19 (d, J = 12.2 Hz, 1H), 5.13 (d, J = 12.2 Hz, 1H), 4.61 (dd, J =

8.5, 4.3 Hz, 1H), 4.57 (q, J = 7.3 Hz, 1H), 3.89 (m, 2H), 3.70 (s, 3H), 3.22 (dd, J = 14.0, 4.3 Hz,

1H), 2.70 (m, 2H), 2.27 (dd, J = 15.2, 9.8 Hz, 1H), 2.18 (m, 1H), 1.44 (d, J = 7.3 Hz, 3H), 0.93 (d, J

= 6.7 Hz, 3H), 0.86 (d, J = 6.7 Hz, 3H); 19F NMR (500 MHz, CDCl3): δ = - 73.7 (d, J = 7.0 Hz); 13C

(500 MHz, CDCl3): δ = 173.6, 172.8, 171.7, 169.1, 136.6, 135.2, 129.0, 128.8, 128.7, 128.6, 128.4,

127.1, 126.1 (q, J = 286.7 Hz), 67.3, 60.5, 57.3, 54.0 (q, J = 27.7 Hz), 52.2, 47.9, 39.9, 36.1, 31.4,

19.1, 17.6, 17.0; MSCI: e/z (%): 580 (100) [M++1].

11: Rf = 0.35 (Hexane/EtOAc 50:50); FTIR (film): νmax = 3298, 1735, 1701 cm-1; 1H NMR


3.74 (m, 1H), 3.69 (d, J = 17.3 Hz, 1H), 3.63 (d, J = 17.3 Hz, 1H), 3.00 (s, 3H), 2.95 (s, 3H), 2.68

(dd, J = 16.2, 2.9 Hz, 1H), 2.57 (dd, J = 16.2, 9.2 Hz, 1H), 2.20 (br s, 1H); 19F NMR (235.4 MHz,

CDCl3): δ = -75.7 (d, J = 7.3 Hz); 13C NMR (127.7 MHz, CDCl3): δ = 171.6, 168.7, 135.5, 128.6,

128.3, 126.4 (q, J = 281.6 Hz), 66.7, 56.7 (q, J = 28.6 Hz), 50.0, 37.2, 35.6, 33.3; MS (70 eV): e/z

(%): 333 (82) [M++1], 197 (70), 92 (100).

12: Rf = 0.41 (CHCl3/MeOH 90:10); FTIR (film): νmax = 3306, 1742, 1739 cm-1; 1H NMR

(500 MHz, CDCl3): δ = 7.77 (br s, 1H), 3.70 (m, 1H), 3.57 (d, J = 17.2 Hz, 1H), 3.47 (d, J = 17.2

Hz, 1H), 3.03 (s, 3H), 3.00 (s, 3H), 2.83 (d, J = 4.7 Hz, 3H), 2.67 (dd, J = 16.2, 2.3 Hz, 1H), 2.51

(dd, J = 16.2, 2.3 Hz, 1H); 19F NMR (235.4 MHz, CDCl3): δ = -75.0 (br s); MS (70 eV): e/z (%):

255 (100) [M++1].

Tests on MMP-9. Cell Culture. Circulating human monocytes were isolated from blood of

healthy donors as previously described[1]. The monocytes were collected, washed, resuspended in

serum free Dulbecco Modified Eagle’s medium (GIBCO BRL, Life Technologies, Italia) and plated

at a density of 3 x 106 cells in 35mm dish. After 2 hr, cell monolayers were washed twice and the

adherent cells were incubated for 10-14 days with DMEM containing 10% human AB serum and

insulin 8 µg/ml, to allow for differentiation in macrophages. To generate the conditioned media,

cells were incubated for 24 hr at 37°C with DMEM, supplemented with 0.2% bovine serum

albumin (BSA; Sigma) and the indicated concentrations of compounds. At the end of the

incubation, the conditioned media were collected and the gelatinolytic capacity of secreted MMP-9

analyzed by zymography [1]. Cellular protein content was measured according to Lowry [2].

SDS Page Zymography. Samples (5 µl of conditioned medium per lane) underwent

electrophoresis at 4 °C on 7.5% polyacrylamide gels containing 10% SDS and gelatin (1 mg/ml)

under non-reducing conditions and without boiling. After electrophoresis, SDS was removed from

gels in two washes with 2.5% Triton X-100 (Sigma) at room temperature. After washes, the gels

were incubated overnight at 37°C with gentle shaking in TRIS 50 mM pH 7.5 containing NaCl 150

mM, CaCl2 10 mM, ZnCl2 1 µM, to activate the metalloproteinase ability to digest the substrate.

For inhibition studies and to confirm the identity of MMP-9, identical gels have been incubated in

the above buffer containing either EDTA 20 mM, an inhibitor of MMPs, or PMSF 1 mM, an

inhibitor of serine proteases. The addition of PMSF did not alter the MMP-9 gelatinolytic capacity,

while the treatment with EDTA completely abolished it (data not shown). At the end of the

incubation, the gels were stained with a solution of 0.1% Coomassie brilliant blue R-250 (Sigma) in

25% methanol and 7% acetic acid. Clear zones against the blue background indicated the presence

of proteinolytic activity[3].

[1] S. Bellosta, D. Via, M. Canavesi, P. Pfister, R. Fumagalli, R. Paoletti, F. Bernini, Arterioscl.

Thromb. Vasc. Biol. 1998, 18, 1671–1678.

[2] O. H. Lowry, N. J. Rosebrough, A. L. Farr, R. J. Randall, J. Biol. Chem. 1951, 193, 265-

275.

[3] Abbreviations: EDTA, Ethylenediaminetetraacetic acid; DMEM, Dulbecco Modified

Eagle’s medium; BSA, Bovine serum albumin; PMSF, Phenylmethylsulfonylfluoride; SDS,

Sodium dodecyl sulfate.

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MeO

2C

CH

3

1 H N

MR

(CD

Cl 3)

(pp

m)

0.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

8.0

NO

OC

F 3

N H 7c

Bn

O

H N

O

MeO

2C

CH

3

1 H N

MR

(CD

Cl 3)

(pp

m)

0.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

8.0

N H

OC

F 3

NBn

O2C

CO

2Me

9aH

1 H N

MR

(CD

Cl 3)

(pp

m)

0.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

N H

OC

F 3

NBn

O2C

CO

2Me

9bH

1 H N

MR

(CD

Cl 3)

(pp

m)

0.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

N H

OC

F 3

NM

eO2C

CO

2Bn

Bn

9cH

1 H N

MR

(CD

Cl 3)

(pp

m)

0.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

N

OC

F 3

NM

eO2C

9dH

CO

2Bn

1 H N

MR

(CD

Cl 3)

(pp

m)

0.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

N H

OC

F 3

NBn

O2C

CO

2Bn

Bn

9eH

1 H N

MR

(CD

Cl 3)

(pp

m)

0.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

8.0

CF 3

N H

Bn

10

H N

O

MeO

2C

Me

N H

O

CO

2Bn

1 H N

MR

(CD

Cl 3)

(pp

m)

0.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

8.0

N

O

N H

CF 3

CO

2Bn

11

H3C

CH

3

1 H N

MR

(CD

Cl 3)

1 H N

MR

(CD

Cl 3)

H3C

NN

NC

H3

CH

3OC

F 3

O

Hb

Ha

12

Documents

Synthesis, Structure and Conformation of Partially-Modified Retro- and Retro-Inversoψ[NHCH(CF3)]Gly Peptides