A. Kamal et al. / Bioorg. Med. Chem. Lett. 14 (2004) 4581–4583
4583
4. (a) Gasparrini, F.; Misiti, D.; Villani, C. J. Chromatogr.
1991, 539, 25; (b) Gubitz, G.; Pierer, B.; Wendelin, W.
Chirality 1992, 4, 333; (c) Lobell, M.; Schneider, M. P. J.
Chromatogr. 1993, 633, 287; (d) In Analytical Profiles of
Drug Substances, 1992; Vol. 21, pp 500–532.
5. Simon, A.; Thomis, J. A. U.S. 5,089,526, 1992.
6. Smith, P.; Brodfuehrer, P. R.; Dillon, J. L.; Vemishetti, P.
Synth. Commun. 1995, 25, 1093.
5.39%. Spectral data for compound 5: 47% yield; >99%
25
ee,23 (tR ¼ 22:02 min); ½a +19.74 (c 1, EtOH) [lit.8b +17.5
D
(c 1, EtOH), 88% ee]; IR (KBr) 1744, 1220 cmÀ1; 1H NMR
(300 MHz, CDCl3) d 2.15 (3H, s), 3.83–3.97 (2H, m), 4.34
(2H, d, J ¼ 5:28 Hz), 5.47 (1H, m), 6.8 (1H, d,
J ¼ 7:17 Hz), 7.3–7.5 (4H, m), 7.75 (1H, m), 8.15 (1H,
m); MS (EI) m=z 278 (Mþ). Anal. Calcd for C15H15O3Cl:
C, 68.57; H, 5.75. Found: C, 68.13; H, 5.43%. Spectral
7. Brodfuehrer, P. R.; Smith, P.; Dillon, J. L.; Vemishetti, P.
Org. Process Res. Dev. 1997, 1, 176.
data for compound 8: white solid, mp 96–98 °C; 52% yield;
25
90% ee,22b (tR ¼ 45:30 min); ½a )19.09 (c 1.03, EtOH);
D
8. (a) Chiou, T.-W.; Chang, C.-C.; Lai, C.-T.; Tai, D.-F.
Bioorg. Med. Chem. Lett. 1997, 7, 433; (b) Bevinakatti, H.
S.; Banerji, A. A. J. Org. Chem. 1991, 56, 5372; (c) Damle,
S. V.; Patil, P. N.; Salunkhe, M. M. Synth. Commun. 1999,
29, 3855; (d) Pamies, O.; Backvall, J.-E. J. Org. Chem.
2001, 66, 4022.
9. (a) Sasai, H.; Itoh, N.; Suzuki, T.; Shibasaki, M. Tetra-
hedron Lett. 1993, 34, 855; (b) Chinchilla, R.; Najera, C.;
Sanchez-Agullo, P. Tetrahedron: Asymmetry 1994, 5, 1393.
10. Sakuraba, S.; Takahashi, H.; Takeda, H.; Achiwa, K.
Chem. Pharm. Bull. 1995, 43, 738.
11. (a) Handson, R. M. Chem. Rev. 1991, 91, 437; (b) Lorrow,
J.; Wasserthal, P. J. Am. Chem. Soc. 1996, 118, 7420.
12. (a) Kamal, A.; Rao, A. B.; Rao, M. V. Tetrahedron Lett.
1992, 33, 4077; (b) Kamal, A.; Damayanthi, Y.; Rao, M.
V. Tetrahedron: Asymmetry 1992, 3, 1361.
IR (KBr) 3400, 1325 cmÀ1; 1H NMR (300 MHz, CDCl3) d
1.67 (1H, br s), 3.02 (3H, s), 3.58–3.67 (1H, dd, J ¼ 8:68,
11.33 Hz), 3.69–3.77 (1H, dd, J ¼ 3:4, 11.33 Hz), 4.9 (1H,
dd, J ¼ 8:68, 3.4 Hz), 7.26 (2H, d, J ¼ 8:6 Hz), 7.4 (2H, d,
J ¼ 8:6 Hz); MS (EI) m=z 215 (Mþ)34). Anal. Calcd for
C9H12NO3ClS: C, 43.29; H, 4.84; N, 5.61; S, 12.84. Found:
C, 43.12; H, 4.38; N, 5.54; S, 12.45%. Spectral data for
compound 9: white solid mp 138–140 °C; 49% yield; 94%
25
ee,22b (tR ¼ 34:15 min); ½a +84.07 (c 0.9, EtOH); IR
D
(KBr) 1728 cmÀ1; 1H NMR (200 MHz, CDCl3) d 2.07 (3H,
s), 2.9 (3H, s), 3.48–3.78 (2H, m), 5.8 (1H, dd, J ¼ 5:2,
7.43 Hz), 7–7.3 (4H, m); MS (EI) m=z 291 (Mþ).
Anal. Calcd for C11H14NO4ClS: C, 49.74; H, 5.57; N,
4.83; S, 11.06. Found: C, 49.22; H, 5.46; N, 4.67; S,
11.04%.
21. Spectral data for compound 1a: white solid mp 70 °C; 95%
25
ee23, (tR ¼ 11:96 min); ½a )8.83 (c 1, EtOH) [lit.8b)9.7 (c
13. Kamal, A.; Rao, A. B.; Rao, M. V. Biochem. Pharmacol.
1991, 41, 1393.
D
1.5, EtOH)]; IR (KBr) 3260, 3030 cmÀ1
;
1H NMR
14. Kamal, A.; Sandbhor, M. Bioorg. Med. Chem. Lett. 2002,
12, 1735.
(300 MHz, CDCl3) d 1.15 (6H, d, J ¼ 6:42 Hz), 2.83–3.08
(3H, m), 3.2 (2H, br s), 4–4.3 (3H, m), 6.77 (1H, d,
J ¼ 6:79 Hz), 7.24–7.5 (4H, m), 7.75 (1H, m), 8.2 (1H, m);
13C NMR (200 MHz, CDCl3) d 154.33, 134.48, 127.44,
126.32, 125.74, 125.58, 125.14, 121.79, 120.54, 104.97,
70.82, 68.58, 49.58, 48.93, 23.12, 22.99; MS (FAB) m=z 260
(Mþ + 1); HRMS data: Calcd for C16H21NO2 260.165054,
15. (a) Kamal, A.; Sandbhor, M.; Ramana, K. V. Tetrahe-
dron: Asymmetry 2002, 13, 815; (b) Kamal, A.; Sandbhor,
M.; Shaik, A. A.; Sravanthi, V. Tetrahedron: Asymmetry
2003, 14, 2839; (c) Kamal, A.; Sandbhor, M.; Ahmad, K.;
Adil, S. F.; Shaik, A. A. Tetrahedron: Asymmetry 2003,
14, 3861; (d) Kamal, A.; Shaik, A. A.; Sandbhor, M.;
Malik, M. S. Tetrahedron: Asymmetry 2004, 15, 935.
16. Kamal, A.; Sandbhor, M.; Shaik, A. A. Tetrahedron:
Asymmetry 2003, 14, 1575.
found 260.165902. Spectral data for compound 1b: white
25
D
solid mp 69–70 °C; 98% ee23, (tR ¼ 20:50 min); ½a +10.5
(c 1, EtOH) [lit.8b +9.8 (c 1.6, EtOH)]. Spectral data for
compound 2a: 90% ee [from the HPLC analysis of the
25
D
17. Martinez, F.; Campo, C. D.; Sinisterra, J. V.; Llama, E. F.
Tetrahedron: Asymmetry 2000, 11, 4651.
precursor (R)-8]22b; ½a (2aÆHCl) )30.6 (c 1, water) [lit.4d
)34.7 (c 1, water)]; IR (KBr) 3570, 3410, 1325 cmÀ1
;
1H
18. (a) Uloth, R. H.; Kirk, J. R.; Gould, A. A. J. Med. Chem.
1966, 9, 88; (b) Olah, G. A.; Kobayashi, S. J. Am. Chem.
Soc. 1971, 93, 2253.
NMR (200 MHz, CD3OD) d 1.24 (6H, d, J ¼ 6:59 Hz), 3.0
(3H, s), 3.14 (1H, m), 3.83 (2H, d, J ¼ 5:12 Hz), 4.3 (1H, t,
J ¼ 5:12 Hz), 7.3 (2H, d, J ¼ 8:78 Hz), 7.45 (2H, d,
J ¼ 8:78 Hz); 13C NMR (200 MHz, CDCl3) d 140.32,
134.13, 130.28, 121.54, 64.61, 62.28, 50.28, 47.72, 39.52,
20.78, 19.40; MS (FAB) m=z 273 (Mþ + 1). Anal. Calcd for
C12H20N2O3ClS: C, 52.92; H, 7.40; N, 10.29; S, 11.77.
Found: C, 52.86%; H, 7.35%; N, 10.20%; S, 11.62%.
19. General procedure for one-pot reduction of 3 and 7 and in
situ lipase resolution: A solution of 3 or 7 (1 mmol),
preactivated neutral aluminium oxide15a (1 g), and sodium
borohydride (2 mmol) in diisopropyl ether was shaken at
40 °C in an orbital shaker for 3–4 h. After the complete
reduction indicated by TLC, PS-C lipase (1 equiv w/w),
isopropenyl acetate (6 mmol) were added and the reaction
was continued until about 50% conversion by HPLC
analysis.23 The reaction was filtered through the pad of
Celite, washed with water and brine and concentrated
under reduced pressure. The crude compound was purified
on column chromatography to get the corresponding
alcohol 4 or 8 and acetate 5 or 9.
Spectral data for compound 2b: 94% ee [from the HPLC
25
D
analysis of the precursor (S)-9]22b; ½a (2bÆHCl) +30.4 (c
1, water) [lit.4d +35.8 (c 1, water)].
22. (a) Enantioselectivity was determined by HPLC (CHIRA-
CEL, AD-H column, Daicel). (a) Employing hexane/
isopropanol ¼ 90/10 as a mobile phase, with 0.5 mL/min
flow rate and monitored at 254 nm wavelength; (b)
Employing hexane/isopropanol/diethylamine ¼ 90/10/0.1
as a mobile phase, with 0.5 mL/min flow rate and
monitored at 254 nm wavelength.
23. Enantioselectivity was determined by HPLC (CHIRA-
CEL, OD column, Daicel) by employing hexane/isopro-
panol/diethylamine ¼ 90/10/0.1 as a mobile phase, with
0.5 mL/min flow rate and monitored at 254 nm wave-
length.
20. Spectral data for compound 4: 50% yield; 96% ee,22a
25
D
(tR ¼ 19:11 min); ½a )8.83 (c 1.0, EtOH) [lit.8b )8.3 (c 1,
EtOH), 92% ee]; IR (neat) 3410, 1220, cmÀ1
;
1H NMR
(200 MHz, CDCl3) d 3.8 (2H, m), 4.2 (3H, m), 6.7 (1H, d,
J ¼ 7:6 Hz), 7.2–7.5 (4H, m), 7.7 (1H, m), 8.2 (1H, m); MS
(EI) m=z 236 (Mþ), 144 (Mþ)92). Anal. Calcd for
C13H13O2Cl: C, 65.97; H, 5.54. Found: C, 65.24; H,