5802
G. Guillerm et al. / Bioorg. Med. Chem. Lett. 14 (2004) 5799–5802
0 0 0 0 0
2.87 (dd, 1H, J4 ,5 b 4.5, J5 b,5 a 16.0, H5 b); 4.11 (dd, 1H,
12. Singh, A. K. Synth. Commun. 1990, 20, 3547.
13. Noe, C. R.; Windhab, N.; Haberhauer, G. Arch. Pharm.
(Weinheim) 1995, 328, 743.
0
J2 ,3 10.0, H3 ); 4.21 (m, 3H, CH2 and H4 ); 4.54 (dm, 2H,
0
0
0
0
JH,F 47.7, CH2); 4.67 (dd, 1H, J1 ,2 5.3, J2 ,3 10.0, H2 );
0
0
0
0
0
0
0
5.84 (d, 1H, J1 ,2 5.3, H1 ); 8.15 and 8.40 (2s, 2H, H2 and
14. (a) Tilekar, J. N.; Patil, N. T.; Dhavale, D. D. Synthesis
2000, 395; (b) Patil, N. T.; Tilekar, J. N.; Dhavale, D. D.
J. Org. Chem. 2001, 66, 1065; (c) Nomoto, S.; Shimoyama,
A. Tetrahedron Lett. 2001, 42, 1753; (d) Kirmse, W. Eur. J.
Org. Chem. 2002, 2193.
13
0
H8). C NMR (DMSO-d6, 62.5MHz, d ppm) 38.0 (C5 );
0
63.4 (d, JC,F 9.3, CH2); 72.6(C 2 ); 72.8 (C3 ); 79.4 (C4 );
0
0
0
81.5 (d, JC,F 83.0, CH2F); 87.6(C 1 ); 119.1; 139.9; 149.3;
152.6; 156.1; 170.7 (C@O). 19F NMR (DMSO-d6,
235MHz, d ppm, J Hz) ꢀ224.4 (tt, 1F, J 30.2, J 47.7).
MS m/z 342 (MH+). HRMS (CI/NH3) calcd for
C13H17N5O5F (MH+) 342.1214, found 342.1237. Com-
15. Epp, J. B.; Widlanski, T. S. J. Org. Chem. 1999, 64, 293.
16. Prasad, R. N.; Fung, A.; Tietje, K.; Stein, H. H.; Brondyk,
H. D. J. Med. Chem. 1976, 19, 1180.
1
1
17. Compound 5: H NMR (CDCl3, 250MHz, d ppm, J Hz)
pound 3a (50/50 mixture of diastereoisomers): H NMR
(DMSO-d6, 250MHz, d ppm, J Hz) 1.80 (m, 1H,
cyclopropyl); 2.04 (m, 1H, cyclopropyl); 2.95 (m, 2H,
0
1.4 (s, 3H); 1.6(s, 3H); 4.7 (m, 1H, H 6 ); 5.5 (dd, 1H, J1 ,2
0
0
0
0
0
0
0
0
0
0
1.0, J2 ,3 6.2, H1 ); 5.6(dd, 1H, J2 ,3 6.2, J3 ,4 2.1, H3 ); 6.3
0
0
0
0 0 0
2H5 ); 4.15 (m, 1H, H3 ); 4.28 (m, 1H, H4 ); 4.48 (m, 1H,
(d, 1H, J1 ,2 1.0, H1 ); 7.5–8.0 (m, 5H, Ar); 8.1 and 8.7 (2s,
2H, H2 and H8). 13C NMR (CDCl3, 62.5MHz, d ppm)
24.9 and 26.5; 53.1 (C60); 83.1 (C30); 83.4 (C20); 90.5 (C40);
91.1 (C10); 114.1; 123.2; 127.7; 127.8; 128.5; 132.5; 132.6;
133.1; 142.4; 149.7; 151.1; 152.3; 164.8 (C@O Bz); 191.4
(C@O diazoketone). MS m/z 450 (MH+).
0
cyclopropyl); 4.77 (dd, 0.5H, J1 ,2 = J2 ,3 5.0, H2 ) and
0
0
0
0
0
0
0
0
0
4.84 (dd, 0.5H, J1 ,2 = J2 ,3 5.0, H2 ); 5.90 (d, 1H, J1 ,2 5.0,
0
0
0
H1 ); 8.15 and 8.17 (2s, 2*0.5H, H2); 8.36and 8.38 (2s,
2*0.5H, H8). 13C NMR (DMSO-d6, 62.5MHz, d ppm)
0
26.0 (CH2 cyclopropyl); 37.5 (C5 ); 56.8 (CH cyclopropyl);
0
0
0
0
18. Aoyama, T.; Shioiri, T. Tetrahedron Lett. 1980, 21, 4461.
19. Wong, H. N. C.; Hon, M. Y.; Tse, C. W.; Yip, Y. C.;
Tanko, J.; Hudlicky, T. Chem. Rev. 1989, 89, 165.
20. Ohba, T.; Tsuchiya, N.; Nishimura, K.; Ikeda, E.;
Wakayama, J.; Takei, H. Bioorg. Med. Chem. Lett.
1996, 6, 543.
72.4 (C3 ); 72.9 (C4 ); 80.1 (C2 ); 87.7 (C1 ); 106.0 (CCl2);
120.0; 140.0; 152.6; 156.0; 170.0 (C@O). MS m/z 404
(MH+). HRMS (CI/NH3) calcd for C14H16N5O5Cl2
(MH+) 404.0528, found 404.0456. Compound 3b (mixture
of diastereoisomers): 1H NMR (DMSO-d6, 250MHz, d
ppm, J Hz) 1.73 (m, 1H, cyclopropyl); 2.00 (m, 1H,
0
cyclopropyl); 2.91 (m, 2H, 2H5 ); 4.22 (m, 1H, cyclopro-
21. Matysiak, S.; Fitznar, H. P.; Schnell, R.; Pfleiderer, W.
Helv. Chim. Acta 1998, 81, 1545.
0
pyl); 4.48 (m, 1H, H4 ); 4.72 (m, 1H, H2 ); 5.90 (d, 1H, J1 ,2
0
0
0
0
22. Bessard, Y.; Muller, U.; Schlosser, M. Tetrahedron 1990,
46, 5213.
5.0, H1 ); 8.10 (s, 1H, H2); 8.30 (s, 1H, H8). 13C NMR
¨
(DMSO-d6, 62.5MHz, d ppm) 17.1 (m, CH2 cyclopropyl);
0 0 0
37.5 (C5 ); 50.9 (m, CH cyclopropyl); 72.5 (C3 ); 72.8 (C4 );
1
23. Compound 2a: H NMR (DMSO-d6, 250MHz, d ppm, J
0
Hz) 2.82 (dd, 1H, J4 ,5 a 8.5, J5 b,5 a 16.0, H5 a); 2.92 (dd,
0
0
0
0
0
0
80.1 (C2 ); 87.7 (C1 ); 107.0 (m, CF2); 119.2; 140.0; 149.3;
152.6; 156.0; 170.3 (C@O). MS m/z 372 (MH+). HRMS
(CI/NH3) calcd for C13H17N5O5F2 (MH+) 372.1119,
found 372.1148.
0
1H, J4 ,5 b 4.8, J5 b,5 a 16.0, H5 b); 3.80 (t, 2H, J 5.4, CH2);
0
0
0
0
0
4.16(m, 1H, H 3 ); 4.27 (m, 3H, CH2 and H4 ); 4.74 (dd,
0
0
0
0
0
0
0
0
0
1H, J1 ,2 5.4, J2 ,3 10.5, H2 ); 5.89 (d, 1H, J1 ,2 5.4, H1 );
8.10 and 8.30 (2s, 2H, H2 and H8). 13C NMR (DMSO-d6,
24. Yuan, C. S.; Yeh, J.; Squier, T. C.; Rawitch, A.;
Borchardt, R. T. Biochemistry 1993, 32, 10414.
25. Kitz, K.; Wilson, I. B. J. Biol. Chem. 1962, 237, 3245.
26. Hohman, R. J.; Guitton, M. C.; Veron, M. Proc. Natl.
Acad. Sci. U.S.A. 1985, 82, 4578.
0
62.5MHz, d ppm) 38.3 (C5 ); 42.8 (CH2); 64.4 (CH2); 72.9
0
0
0
0
(C4 ); 73.2 (C3 ); 80.6(C 2 ); 88.0 (C1 ); 119.5; 140.3; 149.7;
153; 156.4; 170.6 (C@O). MS m/z 358 (MH+). HRMS (CI/
NH3) Calcd for C13H17N5O5Cl (MH+) 358.0918, found
358.0927. Compound 2b: 1H NMR (DMSO-d6, 250MHz,
27. Wnuk, S. F.; Liu, S.; Yuan, C. S.; Borchardt, R. T.;
Robins, M. J. J. Med. Chem. 1996, 39, 4162.
0
0
0
0
0
d ppm, J Hz) 2.76(dd, 1H, J4 ,5 a 9.0, J5 b,5 a 16.0, H5 a);