4584 J ournal of Medicinal Chemistry, 2002, Vol. 45, No. 20
Brief Articles
prolyl-pyrrolidine amide in 10 mL of 50% methanol in water
at 0 °C. The reaction was stirred for 1 h at room temperature.
The methanol was evaporated, and the residue was dissolved
in dichloromethane and saturated NaCl. The phases were
separated, and the dichloromethane phase was washed with
saturated NaCl. The dichloromethane phase was dried and
evaporated.
students Mr. J anne Lo¨tjo¨nen and Mr. Mikko Gynther
for helping us by performing some synthetic steps.
Su p p or tin g In for m a tion Ava ila ble: Complete experi-
mental details. This material is available free of charge via
the Internet at http://pubs.acs.org.
Su ccin ic Acid bis(L-P r olyl-p yr r olid in e) Am id e (1a ). MS
(ESI) m/z ) 419 (MH+). 13C NMR (CDCl3): δ 24.11, 24.67,
26.21, 28.80, 28.87, 45.90, 46.22, 47.15, 57.83, 170.69 (same
shift for both carbonyls). Anal. (C22H34N4O4‚1.4H2O) C, H, N.
Glu ta r ic Acid bis(L-P r olyl-p yr r olid in e) Am id e (1b). MS
(ESI) m/z ) 433 (MH+). 13C NMR (CDCl3): δ 19.80, 24.08,
24.81, 26.16, 28.86, 33.28, 45.86, 46.24, 47.32, 57.69, 170.65,
171.27. Anal. (C23H36N4O4‚0.7H2O) C, H, N.
Ad ip ic Acid bis(L-P r olyl-p yr r olid in e) Am id e (1c). MS
(ESI) m/z ) 447 (MH+). 13C NMR (CDCl3): δ 24.14, 24.29,
24.84, 26.21, 28.87, 34.26, 45.87, 46.28, 47.28, 57.63, 170.75,
171.38. Anal. (C24H38N4O4‚1.0H2O) C, H, N.
3,3-Dim eth yl Glu ta r ic Acid bis(L-P r olyl-p yr r olid in e)
Am id e (1d ). MS (ESI) m/z ) 461 (MH+). 13C NMR (CDCl3):
δ 24.13, 24.94, 26.22, 28.39, 28.86, 34.30, 44.32, 45.91, 46.20,
48.12, 57.72, 170.74, 170.78. Anal. (C25H40N4O4‚1.0H2O) C, H,
N.
Ter ep h t h a lic Acid bis(L-P r olyl-p yr r olid in e) Am id e
(1e). MS (ESI) m/z ) 467 (MH+). 13C NMR (CDCl3): δ 24.19,
25.57, 26.24, 28.98, 46.03, 46.41, 50.24, 58.15, 127.29, 138.00,
168.71, 170.35. Anal. (C26H34N4O4‚0.4H2O) C, H, N.
Isop h th a lic Acid bis(L-P r olyl-p yr r olid in e) Am id e (1f).
MS (ESI) m/z ) 467 (MH+). 13C NMR (CDCl3): δ 24.18, 25.57,
26.25, 28.99, 46.04, 46.42, 50.30, 58.23, 126.06, 128.24, 129.12,
136.60, 168.61, 170.34. Anal. (C26H34N4O4‚0.2H2O) C, H, N.
P h th a lic Acid bis(L-P r olyl-p yr r olid in e) Am id e (1g). MS
(ESI) m/z ) 467 (MH+). 13C NMR (CDCl3): δ 23.30, 23.97,
24.13, 25.19, 25.89, 26.23, 29.09, 30.54, 45.64, 45.79, 45.99,
46.21, 46.86, 49.93, 57.51, 59.19, 126.89, 127.37, 128.26,
128.87, 134.78, 135.60, 168.75, 168.78, 170.45, 170.80. Anal.
(C26H34N4O4‚0.7H2O) C, H, N.
Refer en ces
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Isop h th a lic Acid L-P r olyl-p yr r olid in e L-P r olyl-L-p r o-
lin a l Am id e (2a ). MS (ESI) m/z ) 495 (MH)+. 13C NMR
(CDCl3) δ 24.19, 25.04, 25.52, 25.55, 25.55, 26.24, 28.98, 29.26,
46.04, 46.40, 47.08, 50.27, 50.29, 58.05, 58.24, 64.89, 126.04,
128.30, 128.99, 129.19, 136.34, 136.69, 168.53, 168.73, 170.29,
171.38, 198.92. Anal. (C27H34N4O5‚2.2H2O) C, H, N.
Isop h th a lic Acid L-P r olyl-2(S)-cya n op yr r olid in e L-P r o-
lyl-p yr r olid in e Am id e (2b). MS (ESI) m/z ) 492 (MH)+. 13
C
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NMR (CDCl3) δ 23.01, 24.20, 25.43, 25.56, 26.25, 28.98, 29.80,
30.84, 46.05, 46.42, 46.50, 46.63, 50.27, 50.30, 58.03, 58.25,
118.63, 126.09, 128.36, 128.93, 129.29, 136.12, 136.77, 168.50,
168.83, 170.31, 171.13. Anal. (C27H33N5O4‚1.0H2O) C, H, N.
Isop h t h a lic Acid L-P r olyl-2(S)-(h yd r oxya cet yl)p yr -
r olid in e L-P r olyl-p yr r olid in e Am id e (2c). MS (ESI) m/z )
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26.25, 28.25, 28.77, 28.99, 46.04, 46.41, 47.14, 47.20, 50.28,
58.04, 58.21, 61.16, 67.15, 126.08, 128.29, 128.96, 129.18,
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(C28H36N4O6‚0.4H2O) C, H, N.
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The yields for all synthesis routes mentioned above varied
between 7 and 55%.
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Ack n ow led gm en t. This research was supported by
Finncovery Ltd. and the National Technology Agency
in Finland (TEKES). We also thank Ms. Tiina Koivunen
and Ms. Pa¨ivi Sutinen for their outstanding technical
assistance, Prof. Dr. J ouko Vepsa¨la¨inen for his help in
assigning the NMR spectra, senior assistant Dr. Seppo
Auriola for performing the ESI-MS analysis, and the
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unusual beta-propeller domain regulates proteolysis. Cell 1998,
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J M020966G