E. Forrꢀo, F. F€ul€op / Tetrahedron: Asymmetry 15 (2004) 2875–2880
2879
126.7, 181.3. Analysis: calculated for C7H11NO2: C,
59.56; H, 7.85; N, 9.92; found: C, 59.52; H, 8.07; N,
9.92.
4.6. Ring opening of b-lactam enantiomers 1b–4b with
aqueous HCl
(1S,5R)-1b (0.1 g, 0.92 mmol), (1S,6R)-2b (0.1 g,
1.63 mmol), (1S,6R)-3b (0.1 g, 1.63 mmol) or (1S,8R)-4b
(0.1 g, 0.67 mmol) was dissolved in 18% HCl (7 mL) and
the solution refluxed for 3 h. The solvent was then
evaporated off and the product recrystallized frometh-
1H NMR (400 MHz, D2O) d (ppm) for 3aÆHCl: 2.27–
2.55 (4H, m, 2 · CH2) 3.07–3.11 (1H, m, H-1) 3.90–3.91
(1H, m, H-2) 5.66–5.83 (2H, m, CHCH). 13C NMR
(100.62 MHz, D2O) d (ppm) 24.5, 27.9, 39.8, 46.9, 122.8,
125.9, 176.8. Analysis: calculated for C7H11NO2ÆHCl: C,
47.33; H, 6.81; N, 7.89; found: C, 47.59; H, 6.82; N,
7.93.
anol–diethyl ether, which afforded white crystals of
25
D
(1S,2R)-1cÆHCl {0.13 g, 87%, ½a ¼ þ81:6 (c 0.3, H2O);
25
(168–171 ꢀC); ee 99%}, (1S,2R)-2cÆHCl {0.13 g, 90%;
½a ¼ ꢀ121:4 (c 0.4, H2O); slow melting (192–209 ꢀC);
D
25
D
1H NMR (400 MHz, CDCl3) d (ppm) for 3b: 1.59–2.11
(4H, m, 2 · CH2) 3.49–3.51 (1H, m, H-1) 4.02–4.04 (1H,
m, H-6) 5.94–6.17 (2H, m, CHCH) 6.01 (1H, br s, NH).
13C NMR (100.62 MHz, CDCl3) d (ppm) 22.0, 27.8,
47.7, 48.8, 124.8, 126.8, 171.2. Analysis: calculated for
C7H9NO: C, 68.27; H, 7.37; N, 11.37; found: C, 68.22;
H, 7.32; N, 11.40.
ee 99%}, (1S,2R)-3cÆHCl {0.11 g, 76%, ½a ¼ þ25:8 (c
25
0.4, H2O); slow melting (180–224 ꢀC); ee 99%}, and
(1S,2R)-4cÆHCl {0.1 g, 73%; ½a ¼ ꢀ15:9 (c 0.3, H2O);
D
(a slowly crystallizing oil); ee 98%}. The 1H NMR
(400 MHz, D2O) d (ppm) data for (1S,2R)-1cÆHCl,
(1S,2R)-2cÆHCl, (1S,2R)-3cÆHCl and (1S,2R)-4cÆHCl are
similar to those for (1R,2S)-1aÆHCl, (1R,2S)-2aÆHCl,
(1R,2S)-3aÆHCl and (1R,2S)-4aÆHCl. Anal. found for
(1S,2R)-1cÆHCl: C, 44.11; H, 6.11; N, 8.27. Anal. found
for (1S,2R)-2cÆHCl: C, 47.22; H, 6.84; N, 7.87. Anal.
found for (1S,2R)-3cÆHCl: C, 47.49; H, 6.77; N, 7.65.
Anal. found for (1S,2R)-4cÆHCl: C, 52.51; H, 7.96; N,
6.67.
4.5. Gram-scale resolution of 9-azabicyclo[6.2.0]dec-4-
en-10-one, ( )-4
Following the procedure described above, the reaction
of racemic 4 (1 g, 6.61 mmol) and water (0.12 mL,
6.61 mmol) in diisopropyl ether (40 mL) in the presence
of lipolase (2 g, 50 mg/mL) at 70 ꢀC afforded the unre-
25
acted (1S,8R)-4b (0.47 g, 47%; ½a ¼ ꢀ24:9 (c 0.4,
23
mp 117–
Acknowledgements
D
25
CHCl3); ½a ¼ ꢀ19:9 (c 0.3, MeOH); mp 136–140 ꢀC
D
(recrystallized fromdiisopropyl ether), lit.
The authors acknowledge the receipt of OTKA grants
TS 040888 and T 046440, FKFP grant 0115/2001 and a
ꢀ ꢀ
Bekesy Fellowship for EF (grant no. 181/2002).
119 ꢀC; ee ¼ 99%) and b-amino acid (1R,2S)-4a {0.51 g,
25
46%; ½a ¼ þ23:9 (c 0.3, H2O); mp 218–220 ꢀC
D
(recrystallized fromwater–acetone); ee ¼ 95%} in 7 h.
When 4a (0.1 g) was treated with 18% aqueous
HCl (3 mL), (1R,2S)-4aÆHCl was obtained {0.1 g,
25
82%; ½a ¼ þ14:2 (c 0.35, H2O); mp 194–205 ꢀC,
D
References and notes
ee ¼ 95%}.
ꢀ
ꢀ
1. Besada, P.; Gonzalez-Moa, M. J.; Teran, C.; Santana, L.;
Uriarte, E. Synthesis 2002, 16, 2445–2449.
1H NMR (400 MHz, D2O) d (ppm) for 4a: 1.81–2.58
(8H, m, 4 · CH2) 2.79 (1H, m, H-1) 3.70–3.73 (1H, m,
H-2) 5.72–5.73 (2H, m, CHCH). 13C NMR
(100.62 MHz, D2O) (ppm) 22.9, 24.7, 27.2, 29.8, 45.9,
52.5, 129.6, 129.9, 181.8. Analysis: calculated for
C9H15NO2: C, 63.88; H, 8.93; N, 8.28; found: C, 63.99;
H, 8.81; N, 8.08.
ꢀ
ꢀ
2. Gonzalez-Moa, M. J.; Besada, P.; Teijeira, M.; Teran, C.;
Uriarte, E. Synthesis 2004, 4, 543–548.
3. Gardiner, J.; Anderson, K. H.; Downard, A.; Abell, A. D.
J. Org. Chem. 2004, 69, 3375–3382.
4. Abell, A. D.; Gardiner, J. Org. Lett. 2002, 4, 3663–3666.
€ €
5. Fulop, F. In Studies in Natural Product Chemistry; Atta-ur-
Rahman, Ed.; Elsevier Science Publishers, 2000; Vol. 22,
pp 273–306.
€ €
1H NMR (400 MHz, D2O) d (ppm) for 4aÆHCl: 1.65–
2.35 (8H, m, 4 · CH2) 2.94 (1H, m, H-1) 3.67 (1H, m, H-
2) 5.55–5.62 (2H, m, CHCCH). 13C NMR (100.62 MHz,
D2O) d (ppm) 23.0, 23.7, 26.9, 30.2, 44.6, 51.8, 129.6,
130.9, 177.0. Analysis: calculated for C9H15NO2ÆHCl: C,
52.56; H, 7.84; N, 6.81; found: C, 52.32; H, 7.99; N,
6.79.
6. Fulop, F. Chem. Rev. 2001, 101, 2181–2204, and refer-
ences cited therein.
7. Sorbera, L. A.; Castaner, J.; Bozzo, J. Drugs Fut. 2002, 27,
1049–1055.
8. Krishnaswamy, D.; Govande, V. V.; Gumaste, V. K.;
Bhawal, B. M.; Deshmukh, A. R. A. S. Tetrahedron 2002,
58, 2215–2225.
9. Sleeman, M. C.; MacKinnon, C. H.; Hewitson, K. S.;
Schofield, C. J. Bioorg. Med. Chem. Lett. 2002, 12, 597–
599.
10. Steer, D. L.; Lew, R. A.; Perlmutter, P.; Smith, A. I.;
Aguilar, M. I. Curr. Med. Chem. 2002, 9, 811–822.
11. Brashear, K. M.; Hunt, C. A.; Kucer, B. T.; Duggan, M.
E.; Hartman, G. D.; Rodan, G. A.; Rodan, S. B.; Leu, C.;
Prueksaritanont, T.; Fernandez-Metzler, C.; Barrish, A.;
Homnick, C. F.; Hutchinson, J. H.; Coleman, P. J. Bioorg.
Med. Chem. Lett. 2002, 12, 3483–3486.
1H NMR (400 MHz, CDCl3) d (ppm) for 4b: 1.83–2.02
and 2.30–2.37 (8H, m, 4 · CH2) 3.21–3.24 (1H, m, H-1)
3.74–3.78 (1H, m, H-8) 5.58–5.62 (2H, m, CHCH) 6.16
(1H, br s, NH). 13C NMR (100.62 MHz, CDCl3)
d (ppm) 23.3, 24.4, 24.9, 31.3, 54.0, 54.6, 130.9,
131.6, 172.2. Analysis: calculated for C9H13NO: C,
71.49; H, 8.67; N, 9.26; found: C, 71.62; H, 8.67; N,
9.23.