9888
F. Jam et al. / Tetrahedron 63 (2007) 9881–9889
86%). Rf 0.38 (MeOH/DCM 5:95); IR nmax (KBr/cmꢀ1
)
C17H20N2O2: C, 71.81; H, 7.09; N, 9.85. Found: C,
71.92; H, 7.20; N, 9.81.
1
3440, 1682; mp 236–238 ꢁC; [a]D ꢀ62 (c 1, CH3OH); H
NMR (CDCl3) d 1.27 (dd, 1H, J¼17.1, 2.1 Hz, CCH2CH),
2.18 (dt, 1H, J¼17.6, 2.3 Hz, CCH2CH), 2.40 (dd, 1H,
J¼17.2, 2.2 Hz, CCH2CH), 2.97 (dd, 1H, J¼14.0, 4.0 Hz,
CH2–Ph), 3.04 (dt, 1H, J¼16.8, 2.4 Hz, CCH2CH), 3.26
(dd, 1H, J¼14.0, 4.0 Hz, CH2–Ph), 4.34 (t, 1H, J¼4.2 Hz,
HNCHC), 5.57–5.50 (m, 2H, 2ꢂCH]), 7.33–7.19 (m, 5H,
Ph–H); 13C NMR (CDCl3) d 27.3, 39.2, 56.5, 63.3, 126.0,
126.9, 127.1, 128.3, 130.5, 135.3, 166.7, 171.9. Anal. Calcd
for C15H16N2O2: C, 70.29; H, 6.26; N, 10.93. Found: C,
70.35; H, 6.27; N, 11.01.
Acknowledgements
Financial support was obtained from the Knut and Alice
Wallenberg Foundation and the Swedish Research Council.
References and notes
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Hanessian, S.; McNaughton-Smith, G.; Lombart, H.-G.;
Lubell, W. D. Tetrahedron 1997, 53, 12789–12854; (d)
Gillespie, P.; Cicariello, J.; Olson, G. L. Biopolym. Pept. Sci.
1997, 43, 191–217; (e) Synthesis of Peptides and Peptido-
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4.8.2. (3S,6R)-3-Benzyl-1,4-diazaspiro[5.5]undec-8-ene-
2,5-dione (8b). Compound 7b (50 mg; 0.12 mmol) was
reacted as described in the general procedure. The crude prod-
uct was purified to give 8b as a white solid (28 mg; 83%). Rf
0.41 (MeOH/DCM 5:95); IR nmax (KBr/cmꢀ1) 3444, 1685;
mp 246–248 ꢁC; [a]D ꢀ44 (c 0.1, CHCl3); 1H NMR
(CDCl3) d 1.49 (d, 1H, J¼15.0 Hz, CCH2CH), 1.79 (dd,
1H, J¼13.2, 5.9 Hz, CCH2CH), 1.96–2.07 (m, 1H,
CCH2CH2CH), 2.14–2.24 (m, 2H, CCH2CH2CH), 2.69 (d,
1H, J¼17.9 Hz, CCH2CH2CH), 2.98 (dd, 1H, J¼13.9,
8.2 Hz, CH2–Ph), 3.38 (dd, 1H, J¼13.9, 3.7 Hz, CH2–Ph),
4.28 (dd, 1H, J¼8.4, 3.7 Hz, HNCHC), 5.54–5.61 (m, 1H,
CH]), 5.68–5.77 (m, 1H, CH]), 5.94 (s, 1H, NH), 6.21
(s, 1H, NH), 7.21–7.34 (m, 5H, Ph–H); 13C NMR (CDCl3)
d 20.9, 31.4, 39.6, 45.4, 55.9, 56.4, 123.0, 126.0, 127.7,
129.2, 129.8, 135.3, 166.9, 170.8. Anal. Calcd for
C16H18N2O2: C, 71.09; H, 6.71; N, 10.36. Found: C,
71.10; H, 6.70; N, 10.37.
4.8.3. (3S,6S)-3-Benzyl-1,4-diazaspiro[5.5]undec-8-ene-
2,5-dione (8c). Compound 7c (40 mg; 99 mmol) was reacted
as described in the general procedure. The crude product was
purified to give 8c as a white solid (23 mg; 84%). Rf 0.44
(MeOH/DCM 5:95); IR nmax (KBr/cmꢀ1) 3444, 1685; mp
3. Tullberg, M.; Grøtli, M.; Luthman, K. Tetrahedron 2006, 62,
7484–7491.
1
250–252 ꢁC; [a]D +2 (c 0.3, CHCl3); H NMR (CDCl3)
4. (a) Kasafirek, E.; Rybak, M.; Krejci, I.; Sturc, A.; Krepela, E.;
Sedo, A. Life Sci. 1992, 50, 187–193; (b) Kasafirek, E.; Moural,
J.; Vinsova, J.; Sturc, A.; Taimr, J. Collect. Czech. Chem.
Commun. 1997, 62, 941–947; (c) Vinsova, J.; Kosar, K.;
Kasafirek, E. Collect. Czech. Chem. Commun. 1994, 59, 195–
202; (d) Kuster, G. J. T.; van Berkom, L. W. A.; Kalmoua,
M.; van Loevezijn, A.; Sliedregt, L. A. J. M.; van Steen,
B. J.; Kruse, C. G.; Rutjes, F. P. J. T.; Scheeren, H. W.
J. Comb. Chem. 2006, 8, 85–94; (e) Habashita, H.; Kokubo,
M.; Hamano, S.; Hamanaka, N.; Toda, M.; Shibayama, S.;
Tada, H.; Sagawa, K.; Fukushima, D.; Maeda, K.; Mitsuya,
H. J. Med. Chem. 2006, 49, 4140–4152.
d 1.49 (d, 1H, J¼15.2 Hz, CCH2CH), 1.81 (dd, 2H,
J¼13.1, 6.2 Hz, CCH2CH), 1.98–2.06 (m, 1H,
CCH2CH2CH), 2.15–2.22 (m, 2H, CCH2CH2CH), 2.71 (d,
1H, J¼17.9 Hz, CCH2CH2CH), 3.01 (dd, 1H, J¼13.9,
8.2 Hz, CH2–Ph), 3.41 (dd, 1H, J¼13.9, 3.7 Hz, CH2–Ph),
4.30 (dd, 1H, J¼8.4, 3.7 Hz, HNCHC), 5.52–5.60 (m, 1H,
CH]), 5.63–5.71 (m, 1H, CH]), 6.03 (s, 1H, NH), 6.23
(s, 1H, NH), 7.23–7.36 (m, 5H, Ph–H); 13C NMR (CDCl3)
d 20.7, 31.4, 35.4, 40.6, 56.2, 56.8, 123.1, 126.2, 127.5,
129.2, 129.9, 135.4, 165.9, 170.5. Anal. Calcd for
C16H18N2O2: C, 71.09; H, 6.71; N, 10.36. Found: C,
71.12; H, 6.75; N, 10.31.
5. Hammer, K.; Undheim, K. Tetrahedron 1997, 53, 2309–2322.
˚
6. Carlsson, A.-C.; Jam, F.; Tullberg, M.; Pilotti, A.; Ioannidis, P.;
4.8.4. (S)-3-Benzyl-1,4-diazaspiro[5.6]dodec-9-ene-2,5-
dione (8d). Compound 7d (50 mg; 0.12 mmol) was reacted
as described in the general procedure. The crude product
was purified to give 8d as a white solid (27 mg; 80%). Rf
0.37 (5:95 MeOH:DCM); IR nmax (KBr/cmꢀ1) 3447,
1683; mp 266–268 ꢁC; [a]D +21 (c 0.5, AcOH); 1H
NMR (CDCl3) d 1.35–2.45 (m, 8H, 2ꢂCCH2CH2CH),
2.95–3.42 (m, 2H, CH2-Ph), 4.25–4.30 (m, 1H, HNCHC),
4.82 (br s, 1H, NH), 5.66–5.67 (m, 2H, 2ꢂCH]), 6.25
(br s, 1H, NH), 7.11–7.35 (m, 5H, Ph–H); 13C NMR
(CDCl3) d 23.4, 33.6, 34.3, 38.2, 52.2, 53.3, 61.1, 127.6,
128.5, 129.1, 130.8, 135.2, 166.8, 171.1. Anal. Calcd for
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5201.
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1, 953–956.
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