R. Csuk, B. Woeste / Tetrahedron 64 (2008) 9384–9387
9387
under diminished pressure to result in oily 10 (1.35 g, 95%). An
analytical sample was obtained after flash chromatography (silica
cussions. Financial support by the ‘Fonds der Chemischen Industrie’
is gratefully acknowledged.
gel, hexane/ethyl acetate 5:1/2:1/1:1); R
f
¼0.45 (hexane/ethyl
¼3418 br s, 2962 s, 2878 s, 1771 m, 1732 s,
463 m, 1382 m, 1180 m, 1156 m, 1120 s, 1071 s, 1036 s, 938 s, 900 m,
acetate 1:2); IR (film):
n
References and notes
1
8
60 m; 1H NMR (300 MHz, CDCl
):
–C(5)), 4.01 (dd, J¼9.4, 3.2 Hz, 1H,
–C(5)), 3.12–3.07 (m, 1H, H–C(4)), 2.67 (dd, J¼18.7, 4.5 Hz, 1H,
–C(8)), 2.50 (dd, J¼10.3,
–C(6)), 1.50–1.35 (m, 1H,
d
¼9.84 (s, 1H, H–C(9)), 4.34
1. Byasson, M. Pharm. J. 1875, 5, 826.
3
2
. (a) Gerrard, A. W. Pharm. J. 1875, 5, 865; (b) Gerrard, A. W. Pharm. J. 1875, 5, 965;
c) Gerrard, A. W. Pharm. J. 1875, 6, 227; (d) Gerrard, A. W. Pharm. J. 1876, 7, 255.
. Hardy, E. Bull. Soc. Chim. Fr. 1875, 24, 497.
(
H
ddd, J¼9.4, 5.8, 0.9 Hz, 1H, H
A
(
B
3
H–C(3)), 2.55 (dd, J¼10.3, 3.7 Hz, 1H, H
.6 Hz, 1H, H –C(8)), 1.86–1.78 (m, 1H, H
–C(6)), 1.05 (t, J¼7.4 Hz, 3H, H–C(7)); C NMR (75 MHz, CDCl
A
4. Harnack, E.; Meyer, H. Liebigs Ann. Chem. 1880, 204, 67.
5
. (a) Petit, A.; Polonovski, M. Bull. Soc. Chim. Fr. 1897, 17, 554; (b) Petit, A.; Polo-
novski, M. Pharm. J. 1897, 5, 370; (c) Petit, A.; Polonovski, M. Pharm. J. 1898, 6, 8.
. Holmes, E. M. Pharm. J. 1895, 1, 520.
1
H
B
A
1
3
B
3
):
6
d
¼199.19 (d, CHO), 177.65 (s, CO), 70.51 (t, C(5)), 44.24 (d, C(3)),
7. Chemnitius, F. J. Prakt. Chem. 1928, 118, 20.
8. Paul, B. H.; Cownley, A. J. Pharm. J. 1896, 3, 1.
3
8
4.60 (d, C(4)), 26.46 (t, C(8)), 18.55 (t, C(6)), 12.02 (q, C(7)); MS (EI,
9. (a) Cownley, A. J. Pharm. J. 1904, 18, 54; (b) Jowett, H. A. D.; Pyman, F. L. Proc.
Chem. Soc. 1912, 28, 268; (c) Holmes, E. M. Pharm. J. 1903, 17, 713.
ꢂ
0 eV, 76 C): m/z¼158 (Mþ2, 8.5), 157 (Mþ1, 8.5), 156 (M, 0.7), 155
(
(
(
Mꢁ1, 1.1), 112 (14.5), 97 (24.6), 85 (39), 69 (76.1), 68 (40.4), 57
10. Reuter, G.; Maerkisch, U.; Hering, V.; Gizella, P.; Szoke, E.; Spasova, N. Ger. (East)
DD287731A5, 1995; Chem. Abstr. 1991, 115, 7008.
61.6), 55 (99.6), 43 (42.1), 41 (100). Anal. Calcd for C
8 12 3
H O
1
1
1
1
1. Brosky, M. E. J. Support. Oncol. 2007, 5, 215.
2. Ramos-Casals, M.; Brito-Zeran, P. Expert Rev. Clin. Immunol. 2007, 3, 195.
3. Edwards, R. S. Curr. Med. Res. Opin. 1997, 13, 501.
4. Tschitschibabin, A. E.; Preobrashenski, N. A. Ber. Dtsch. Chem. Ges. 1930, 63, 460.
5. Preobrashenski, N. A.; Wompe, A. F.; Preobrashenski, W. A. Ber. Dtsch. Chem. Ges.
933, 66, 1187.
6. Preobrashenski, N. A.; Kabatschnik, M. J. Ber. Dtsch. Chem. Ges. 1933, 66, 1541.
7. Preobrashenski, N. A.; Poljakokowa, A. M.; Preobrashenski, W. A. Ber. Dtsch.
Chem. Ges. 1935, 68, 850.
156.18): C, 61.52; H, 7.74. Found: 61.63; H, 7.83.
1
3
5
.8. (D)-(3S,4R)-3-Ethyl dihydro-4-[(1-methyl-1H-imidazol-
-yl)methyl]furan-2(3H)-on, (D)-pilocarpine [(D)-1]
1
1
1
To a mixture of (þ)-10 (1.2 g, 7.7 mmol) and dry K
2 3
CO (3.2 g,
1
8. Preobrashenski, N. A.; Poljakokowa, A. M.; Preobrashenski, W. A. Ber. Dtsch.
Chem. Ges. 1936, 69, 1835.
3
8.5 mmol) in abs dichloromethane/benzene (1:1, 150 ml) a 2.3 M
solution of methylamine in benzene (3.9 ml, 9 mmol) was added.
After stirring for 3 h the solvent was removed under diminished
pressure, dichloromethane (20 ml) was added and removed. Then
p-toluenesulfonylmethylisocyanide (3.31 g, 38.5 mmol) and triethyl-
1
9. Preobrashenski, N. A.; Wompe, A. F.; Preobrashenski, W. A.; Schtschukina, M. N.
Ber. Dtsch. Chem. Ges. 1933, 66, 1536.
20. Poljakokowa, A. M.; Preobrashenski, W. A.; Preobrashenski, N. A. Ber. Dtsch.
Chem. Ges. 1936, 69, 1314.
21. Dey, A. N. J. Chem. Soc. 1937, 137, 1057.
amine (5.4 ml, 38.5 mmol) were added and the mixture was stirred at
22. (a) Chumachenko, A. V.; Maurit, W. E.; Treboganov, A. D.; Smirnova, G. V.;
Teplinskaya, R. B.; Vokova, L. V.; Zvankova, E. N.; Preobrashenski, N. A. Dokl.
Akad. Nauk SSSR 1968, 178, 1352; (b) Chumachenko, A. V.; Zvonkova, E. N.;
Preobrashenski, N. A. J. Org. Chem. USSR (Engl. Transl.) 1972, 8, 1112; (c) Chu-
machenko, A. V.; Zvonkova, E. N.; Preobrashenski, N. A. J. Org. Chem. USSR (Engl.
Transl.) 1969, 5, 571.
23. (a) DeGraw, J. I.; Engstr o¨ m, J. S.; Willis, E. J. Pharm. Sci. 1975, 64, 1700; (b)
DeGraw, J. I. Tetrahedron 1972, 28, 967.
24. Horne, D. A.; Fugmann, B.; Yakushijin; B u¨ chi, G. J. Org. Chem. 1993, 58, 62.
ꢂ
25 C for 7 days. The solvents were removed and the residue was
subjected to chromatography (silica gel, methanol/dichloromethane
1.25%/2.5%/5%)) to afford (þ)-1 (0.96 g, 60%) as a colorless oil.
¼0.58 (CH Cl /MeOH/aq NH OH(25%) 95:4:1), [ þ115.58 (c 1.2,
CHCl ) (lit.: [
þ91 (0.01, EtOH),
by HPLC: Chiralcel OC, hexanes/ethanol 3:7, 0.3 ml/min, UV–vis
¼215 nm, t (þ)-1¼47.1 min, t (ꢁ)-1¼52.32 min; in hexanes/eth-
anol (1:1), t (ꢁ)-1¼70.8 min); IR (film): ¼3374
(þ)-1¼62.06 min, t
w, 3116 w, 2965 m, 2879 m, 1770 s, 1654 w, 1559 w, 1505 m, 1458 m,
424 w, 1374 m, 1315 w, 1290 w, 1271 w, 1224 m, 1176 s, 1109 m,
052 m, 1023 m, 981 m, 948 w, 924 w, 813 w, 733 w, 703 w, 664 m;
(
R
f
2
2
4
a]
D
þ106 (CHCl
4
8
49
3
a
]
D
[a
]
D
3
) ), ee >99%
(
25. Shapiro, G.; Chenzhi, C. Tetrahedron Lett. 1992, 33, 2447.
26. Link, H.; Bernauer, K. Helv. Chim. Acta 1972, 55, 1053.
27. Damon, R. E.; Coppola, G. M. Tetrahedron Lett. 1990, 31, 2849.
l
R
R
R
R
n
28. Lin, H.-J.; Bukownik, R. R.; Pednekar, P. R. Synth. Commun. 1981, 11, 599.
29. (a) Noordam, A.; Maat, L.; Beyerman, H. C. Recl. Trav. Chim. Pays-Bas 1981, 100,
1
1
4
41; (b) Noordam, A.; Maat, L.; Beyerman, H. C. Recl. Trav. Chim. Pays-Bas 1979,
98, 467.
1
H NMR (300 MHz, CDCl
H, C]CH–N), 4.21 (dd, J¼9.2, 5.6 Hz, 1H, CH–CH
J¼9.2, 2.7 Hz,1H, CH–CH –O), 3.58 (s, 3H, N–CH ), 2.86–2.74 (m,1H,
CH–CH–CH –CHO), 2.63 (dd,
), 2.70 (dd, J¼15.3, 3.9 Hz, 1H, CH–CH
J¼8.4, 6.8 Hz, 1H, CO–CH–CH), 2.42 (dd, J¼15.3, 12.0, 1H, CH–CH
CHO), 1.96–1.81 (m, 1H, CH–CH –CH ), 1.68–1.50 (m, 1H, CH–CH
CH –CH
), 1.12 (t, J¼7.5, 3H, CH–CH
¼177.92 (s, CO), 138.32 (d, N]CH–N–CH
27.07 (d, C]CH–N), 69.91 (t, CH–CH –O), 44.86 (d, CO–CH–CH),
7.86 (d, CH–CH–CH ), 31.32 (q, N–CH
8.34 (t, CH–CH –CH ), 12.22 (q, CH –CH
3
):
d
¼7.42 (s, 1H, N]CH–N–CH
3
), 6.80 (s,
–O), 4.09 (dd,
30. Beyerman, H. C.; Maat, L.; van Zon, A. Recl. Trav. Chim. Pays-Bas 1972, 91, 246.
1
2
31. Noordam, A.; Maat, L.; Beyerman, H. C. Recl. Trav. Chim. Pays-Bas 1978, 97, 293.
3
3
3
2. Olofson, R. A.; Kendall, R. V. J. Org. Chem. 1970, 35, 2246.
3. Compagnone, R. S.; Rapoport, H. J. Org. Chem. 1986, 51, 1713.
4. Dominguez, X. A.; Cavazos-Lopez, I.; Franco, R. J. Org. Chem. 1961, 26, 1625.
2
3
2
2
2
2
–
–
35. Dunn, D. L.; Scott, B. S.; Dorsey, E. D. J. Pharm. Sci. 1981, 70, 446.
6. Duhamel, L.; Duhamel, P.; Launay, J.-C.; Plaquevent, J.-C. Bull. Soc. Chim. Fr. 1984,
21.
7. Takano, S.; Uchida, W.; Hatakeyama, S.; Ogasawara, K. Chem. Lett. 1982, 733.
3
2
3
4
13
3
2
3
); C NMR (90 MHz, CDCl
3
):
3
d
3
), 128.64 (s, CH –C]CH),
2
38. (a) Dener, J. M.; Zhang, L.-H.; Rapoport, H. J. Org. Chem. 1993, 58, 1159; (b) Wolf,
J.-P.; Rapoport, H. J. Org. Chem. 1989, 54, 3164; (c) Dunn, P. J.; H a¨ ner, R.; Ra-
poport, H. J. Org. Chem. 1990, 55, 5017.
1
3
1
2
3
3
), 21.40 (t, CH–CH
2
–CHO),
39. Gmeiner, P.; Feldmann, P. L.; Chu-Mayer, M. Y.; Rapoport, H. J. Org. Chem. 1990,
55, 3068.
ꢂ
2
3
2
3
); MS (EI, 80 eV, 90 C):
40. Brecker, L. Dissertation. University of Dortmund, 1996.
m/z¼209 (Mþ1, 1.7), 208 (M, 10.9), 151 (0.5), 149 (0.7), 135 (0.6), 133
41. Percival, K. J. Dissertation. University of Bath, 1991.
(
(
0.7), 124 (0.7), 123 (1.8), 122 (1.1), 121 (2.9), 110 (1.0), 109 (10.2), 108
0.7), 107 (0.5), 97 (1.5), 96 (27.5), 95 (100). Anal. Calcd for
42. Marshall, J. A.; Belletire, J. E. Tetrahedron Lett. 1971, 13, 871.
43. Reimann, E. Eur. Pat. Appl. EP 647 640, 1995; Chem. Abstr. 1995, 123, 33492.
44. (a) Lei, A.; He, M.; Zhang, X. J. Am. Chem. Soc. 2002, 124, 8198; (b) Wang, Z.; Lu,
X. Tetrahedron Lett. 1997, 29, 5213.
C
11
H
16
N
2
O
2
(208.26): C, 63.44; H, 7.74; N, 13.45. Found: C, 63.37; H,
7.83; N, 13.36.
4
4
5. Drysdale, J. J.; Stevenson, H. B.; Sharkey, W. H. J. Am. Chem. Soc. 1959, 81, 4908.
6. (a) Saari, W. S.; Fischer, T. E. Synthesis 1990, 453; (b) Fehrentz, J.-A.; Castro, B.
Synthesis 1983, 676; (c) Goel, O. P.; Krolls, U.; Stier, M.; Kesten, S. Org. Synth.
1988, 67, 69.
Acknowledgements
47. van Leusen, A. M.; Wildemany, J.; Oldenziel, O. H. J. Org. Chem. 1977, 42, 1153.
4
4
8. Polonovski, M.; Polonovski, M. Bull. Soc. Chim. Fr. 1922, 31, 1314.
9. K o¨ hling, R.; L u¨ cke, A.; Nagao, T.; Speckmann, E.-J.; Avoli, M. Neurosci. Lett. 1995,
201, 87.
We like to thank Dr. Hanns Wurziger (Merck KGaA, Darmstadt)
for the donation of natural pilocarpine and for many helpful dis-