Deprotection of the α-Amino and Carboxy Functions of Amino Acid and Dipeptide Methyl Esters
(m, 5 H, Ar-H) ppm. 13C NMR: δ ϭ 22.1, 22.6, 22.9, 37.0, 41.2, Compound 6c: White solid (0.31 g, 75% yield), m.p. 183Ϫ186 °C.
FULL PAPER
51.1, 51.9, 53.2, 126.0, 127.8, 128.7, 139.5, 170.7, 171.6, 171.8 ppm.
IR (KBr): ν˜ ϭ 3408, 2961, 1692, 1656, 1254, 759, 740 cmϪ1 1H
.
EI-MS: m/z (%) ϭ 334 (2) [Mϩ·], 162 (40), 128 (74), 86 (100), 44 NMR ([D6]DMSO): δ ϭ 0.78Ϫ0.94 [m, 6 H, CH(CH3)2], 2.05 [m,
(17), 43 (14). C18H26N2O4 (334.41): calcd. C 64.65, H 7.84, N 8.38, 1 H, CH(CH3)2], 2.70Ϫ3.00 (m, 2 H, CH2Ph), 4.03Ϫ4.31 [m, 4 H,
O 19.14; found C 64.75, H 7.81, N 8.34.
Fmoc-CH2, Fmoc-CH, CHCH(CH3)2], 4.37 (m, 1 H, CHCH2Ph),
7.13Ϫ7.90 (m, 15 H, OCONH, CHCONH, Ar-H) ppm. FABϩ MS:
m/z (%) ϭ 487 (13) [M ϩ H]ϩ, 179 (100), 178 (64), 165 (29).
C29H30N2O5 (486.56): calcd. C 71.59, H 6.21, N 5.76, O 16.44;
found C 71.71, H 6.17, N 5.73.
Compound 5b: Yellow solid (0.40 g, 73% yield), m.p. 112Ϫ114 °C.
IR (KBr): ν˜ ϭ 3278, 2963, 1744, 1672, 1643, 1264 cmϪ1. 1H NMR
(CDCl3): δ ϭ 0.91 [d, J ϭ 2.8 Hz, 3 H, CH2CH(CH3)2], 0.93 [d,
J ϭ 2.9 Hz, 3 H, CH2CH(CH3)2], 0.96 [d, J ϭ 6.6 Hz, 3 H,
CH(CH3)2], 0.99 [d, J ϭ 6.5 Hz, 3 H, CH(CH3)2], 1.50Ϫ1.70 [m, 3
H, CH2CH(CH3)2], 2.01 (s, 3 H, CH3CONH), 2.07 [m, 1 H,
CH(CH3)2], 3.73 (s, 3 H, OCH3), 4.40 [dd, J1 ϭ 7.2, J2 ϭ 8.9 Hz,
1 H, CHCH(CH3)2], 4.55 [m, 1 H,CHCH2CH(CH3)2], 6.55 (d, J ϭ
8.9 Hz, 1 H, OCONH), 6.85 (d, J ϭ 7.7 Hz, 1 H, CHCONH) ppm.
13C NMR: δ ϭ 18.3, 18.9, 21.8, 22.7, 23.2, 24.7, 31.5, 40.9, 50.9,
52.2, 58.2, 170.1, 171.5, 173.1 ppm. EI-MS: m/z (%) ϭ286 (1)
[Mϩ·], 230 (5), 144 (85), 100 (14), 86 (38), 72 (100), 55 (11), 43 (17).
C14H26N2O4 (286.37): calcd. C 58.72, H 9.15, N 9.78, O 22.35;
found C 58.82, H 9.11, N 9.74.
[1]
For a comprehensive review, see: E. Haslam, Tetrahedron 1980,
36, 2409Ϫ2434.
[2]
R. W. Roeske, The Peptides, Academic Press, New York, 1981,
vol. 3, p. 102.
J. Jones, The Chemical Synthesis of Peptides, Clarendon Press,
[3]
Oxford, 1991, p. 103.
M. Bodanzski, Principles of Peptide Synthesis, Springer-Verlag,
[4]
Berlin, 1984, 2nd ed., p. 221.
[5]
S. Liu, C. Dockendorff, S. D. Taylor, Org. Lett. 2001, 3,
1571Ϫ1574.
[6]
B. Ye, T. R. Burke, Tetrahedron Lett. 1995, 36, 4733Ϫ4736.
[7]
R. Pascal, R. Sola, Tetrahedron Lett. 1998, 39, 5031Ϫ5034.
[8]
Compound 5c: Oil (0.53 g, 74% yield). IR (neat): ν˜ ϭ 3287, 3055,
M. G. Organ, J. Xu, B. N’Zemba, Tetrahedron Lett. 2002, 43,
2959, 1746, 1658, 1635, 1263 cmϪ1 1H NMR (CDCl3): δ ϭ 0.82
.
8177Ϫ8180.
[9]
R. W. Jackson, Tetrahedron Lett. 2001, 42, 5163Ϫ5165.
[d, J ϭ 6.8 Hz, 3 H, CH(CH3)2], 0.90 [d, J ϭ 6.8 Hz, 3 H,
CH(CH3)2], 2.01 (s, 3 H, CH3CONH), 2.08 [m, 1 H, CH(CH3)2],
3.00Ϫ3.10 (m, 2 H, CH2Ph), 3.70 (s, 3 H, OCH3), 4.45 [dd, J1 ϭ
5.0, J2 ϭ 8.1 Hz, 1 H, CHCH(CH3)2], 4.70 (m, 1 H, CHCH2Ph),
6.23 (d, J ϭ 7.5 Hz, 1 H, OCONH), 6.32 (d, J ϭ 8.1 Hz, 1 H,
CHCONH), 7.20Ϫ7.38 (m, 5 H) ppm. 13C NMR: δ ϭ 17.7, 18.7,
29.7, 31.1, 38.2, 40.7, 52.2, 54.5, 57.4, 112.7, 116.7, 127.0, 128.7,
170.2, 171.2, 172.8 ppm. EI-MS: m/z (%) ϭ 320 (4) [Mϩ·], 162 (78),
114 (31), 43 (100). C17H24N2O4 (320.38): calcd. C 63.73, H 7.55, N
8.74, O 19.98; found C 63.84, H 7.52, N 8.70.
[10]
M. J. O’Donnell, F. Delgado, Tetrahedron 2001, 57,
6641Ϫ6650.
[11]
Y-Q. Wu, D. C. Limburg, D. E. Wilkinson, M. J. Vaal, G. S.
Hamilton, Tetrahedron Lett. 2000, 41, 2847Ϫ2849.
[12]
G. M. Makara, G. R. Marshall, Tetrahedron Lett. 1997, 38,
5069Ϫ5072.
[13]
C. W. West, M. A. Estiarte, D. H. Rich, Org. Lett. 2001, 3,
1205Ϫ1208.
D. Filippov, E. K. Yeheskiely, G. A. van der Marel, G. I. Tesser,
[14]
J. H. van Boom, Tetrahedron Lett. 1998, 39, 3597Ϫ3600.
[15]
K. J. Hale, J. Cai, V. M. Delisser, Tetrahedron Lett. 1996, 37,
Removal of the Methyl Ester Group of Dipeptides 4aϪc:[22] Removal
of the methyl ester group of the dipeptides 4aϪc (1 mmol) was
carried out with the reagent system AlCl3 (9 mmol)/N,N-dimeth-
ylaniline (15 mmol). Chromatographic purification of the crude
reaction products afforded the respective N-Fmoc-dipeptides 6aϪc
in high yields. The compound characterization data for 6b fitted
those observed for an authentic sample of N-Fmoc-valyl-leucine.[22]
9345Ϫ9348.
[16]
W.-C. Chen, M. D. Vera, M. M. Joullie, Tetrahedron Lett. 1997,
38, 4025Ϫ4028.
M. Nishizawa, H. Yamamoto, K. Seo, H. Imagawa, T. Sugih-
[17]
ara, Org. Lett. 2002, 4, 1947Ϫ1949.
[18]
Y. Luo, M. A. Blaskovich, G. A. Lajoie, J. Org. Chem. 1999,
64, 6106Ϫ6111.
P. Gomez-Martinez, A. M. Kimbonguila, F. Guibe, Tetra-
[19]
hedron 1999, 55, 6945Ϫ6960.
[20]
Compound 6a: White solid (0.25 g, 78% yield), m.p. 167Ϫ170 °C.
IR (KBr): ν˜ ϭ 3390, 2962, 1707, 1670, 1646, 1554, 1246, 761, 740
J. M. Sanderson, P. Singh, C. W. G. Fishwick, J. B. C. Findlay,
J. Chem. Soc., Perkin Trans. 1 2000, 3227Ϫ3231.
J. M. Caba, I. M. Rodriguez, I. Manzanares, E. Giralt,
F. Albericio, J. Org. Chem. 2001, 66, 7568Ϫ7574.
M. L. Di Gioia, A. Leggio, A. Le Pera, C. Siciliano, G.
Sindona, A. Liguori, J. Pept. Res. 2004, 63, 383Ϫ387.
A. Leggio, A. Liguori, A. Napoli, C. Siciliano, G. Sindona,
Eur. J. Org. Chem. 2000, 573Ϫ575.
M. L. Di Gioia, A. Leggio, A. Liguori, A. Napoli, C. Siciliano,
[21]
cmϪ1
. δ ϭ 0.73Ϫ0.89 [m, 6 H,
1H NMR ([D6]DMSO):
CH2CH(CH3)2], 1.41Ϫ1.70 [m, 3 H, CH2CH(CH3)2], 2.92Ϫ3.02
(m, 2 H, CH2Ph), 3.98Ϫ4.38 (m, 4 H, Fmoc-CH2, Fmoc-CH,
CHCH2Ph), 4.72 [m, 1 H, CHCH2CH(CH3)2], 7.08Ϫ8.29 (m, 15
H, OCONH, CHCONH, Ar-H) ppm. FABϩ MS: m/z (%) ϭ 501
(17) [M ϩ H]ϩ, 179 (100), 178 (62), 165 (40). C30H32N2O5 (500.59):
calcd. C 71.98, H 6.44, N 5.60, O 15.98; found C 72.09, H 6.40,
N 5.57.
[22]
[23]
[24]
G. Sindona, J. Org. Chem. 2001, 66, 7002Ϫ7007.
Received May 7, 2004
Eur. J. Org. Chem. 2004, 4437Ϫ4441
2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4441