SYNTHESIS
Papers
618
dd, J = 17.6, 1.0 Hz, CH=CHH), 4.91 (1 H, dd, J = 10.7, 1.0 Hz,
CH=CHH), 3.91 (3 H, s, CO2CH3), 3.66 (1 H, m, NCHH), 3.61 (1 H,
m, NCHH), 2.95 (1 H, d, J = 5.1 Hz, CHNH), 2.67 (3H, s, CH3), 2.63
(3 H, s, CH3), 2.22 (1 H, m, NCHCH2), 2.17 (1 H, m, CH2CHHCH2),
2.01 (1 H, m, CH2CHHCH2), 1.90 (1 H, br, NH), 1.75 [1 H, m,
CH(CH3)2], 1.12 [3 H, s, C(CH3)CH3], 1.10 [3 H, s, C(CH3)CH3],
0.97 [3 H, d, J = 6.8 Hz, CH(CH3)CH3], 0.85 [3 H, d, J = 6.8 Hz,
CH(CH3)CH3].
OCH2), 3.66 (1 H, m, NCHH), 3.61 (1 H, m, NCHH), 2.95 (1 H, d, J
= 5.1 Hz, CHNH), 2.66 (3 H, s, CH3), 2.63 (3 H, s, CH3), 2.22 (1 H,
m, NCHCH2), 2.16 (1 H, m, CH2CHHCH2), 2.00 (1 H, m,
CH2CHHCH2), 1.78 [3 H, s, CH=C(CH3)CH3], 1.77 [3 H, s,
CH=C(CH3)CH3], 1.74 [1 H, m, CH(CH3)2], 1.58 (1 H, br, NH), 1.12
[3 H, s, C(CH3)CH3], 1.10 [3 H, s, C(CH3)CH3], 0.97 [3 H, d, J = 6.7
Hz, CH(CH3)CH3], 0.85 [3 H, d, J = 6.7 Hz, CH(CH3)CH3].
13C NMR (125.8 MHz; CDCl3): δ = 175.96 (s), 163.10 (s), 162.42 (s),
155.54 (s), 154.09 (s), 150.05 (s), 147.92 (d), 139.10 (s), 128.52 (s),
124.66 (s), 118.57 (d), 111.01 (t), 61.81 (t), 59.12 (d), 54.51 (d), 54.16
(s), 46.69 (t), 31.98 (d), 30.60 (t), 28.05 (q), 26.21 (q), 25.80 (q),
24.98 (t), 19.72 (q), 18.13 (q), 17.55 (q), 12.16 (q), 11.77 (q).
LRMS (FAB): m/z(%) = 513 (MH+, 27), 445 (13), 391 (9), 307 (8),
154 (58), 136 (42).
13C NMR (125.8 MHz; CDCl3): δ = 175.95 (s), 163.13 (s), 162.79 (s),
155.81 (s), 154.14 (s), 150.05 (s), 147.88 (d), 128. 20 (s), 124.59 (s),
111.00 (t), 59.13 (d), 54.49 (d), 54.17 (s), 51.88 (q), 46.68 (t), 31.95
(d), 30.59 (t), 28.04 (q), 26.19 (q), 24.96 (t), 19.70 (q), 17.55 (q),
12.04 (q), 11.75 (q).
LRMS (CI, methane): m/z(%) = 459 (MH+, 83), 391 (100), 348 (12),
292 (5), 167 (4), 140 (60), 113 (6).
HRMS (FAB): m/z found MH+, 513.3067; C28H41O5N4 requires
513.3077.
HRMS (CI, methane): m/z found MH+, 459.2584; C24H35O5N4 re-
quires 459.2607.
UV (EtOH): λmax (ε) = 204 nm (13199), 254 (13222).
We thank the EPSRC for a studentship (to JCM) and Zeneca Phar-
Muscoride A (1):
maceuticals for support via a CASE-EPSRC award.
1N NaOH solution (65 µL, 0.07 mmol) was added dropwise to a so-
lution of the methyl ester 6 (12 mg, 0.03 mmol) in THF/MeOH (3:1,
135 µL) and the mixture was stirred for 2 h. The solvents were re-
moved in vacuo to leave a residue which was diluted with H2O (0.5
mL) and neutralised using 1N HCl solution. The mixture was extract-
ed with EtOAc (5 × 5 mL) and the combined extracts were dried and
evaporated in vacuo to give 2-[4'-2'-[N-[N-(1,1-dimethylallyl)-L-va-
lyl]-L-prolyl]-5'-methyloxazole]-5-methyloxazole-4-carboxylic acid
as a colourless gum which was used without further purification; [α]D
–41.3 (c = 0.18, CHCl3).
(1) Nagatsu, A.; Kajitani, H.; Sakakibara, J. Tetrahedron Lett.
1995, 36, 4097.
(2) Ichiba, T.; Yoshida, W. Y.; Scheuer, P. J.; Higa, T.; Gravalos,
D. G. J. Am. Chem. Soc. 1991, 113, 3173.
For synthetic studies with this compound, see:
Barrett, A. G. M.; Kohrt, J. T. Synlett 1995, 415.
Wipf, P.; Lim, S. Chimia 1996, 50, 157.
IR (film): ν = 3354, 2922, 1718, 1650, 1416, 1058 cm–1.
1H NMR (500 MHz; CDCl3): δ = 5.87 (1 H, dd, J = 17.5, 10.9 Hz,
CH=CH2), 5.22 [1 H, m, CH(oxazole)], 5.10 (1 H, d, J = 17.5 Hz,
CH=CHH), 5.06 (1 H, d, J = 10.9 Hz, CH=CHH), 3.70 (1 H, m,
NCHH), 3.62 (1 H, m, NCHH), 3.22 (1 H, br, CHNH), 2.68 (3 H, s,
CH3), 2.62 (3 H, s, CH3), 2.28 (1 H, m, NCHCHH), 2.20 (1 H, m,
NCHCHH), 2.20 (1 H, m, CH2CH2CH2), 2.03 [1 H, m, NH,
CH(CH3)2], 1.32 [3 H, s, C(CH3)CH3], 1.26 [3 H, s, C(CH3)CH3],
1.03 [3 H, d, J = 6.6 Hz, CH(CH3)CH3], 0.96 [3 H, d, J = 6.6 Hz,
CH(CH3)CH3].
Cheng, Z. Z.; Hamada, Y.; Shioiri, T. Synlett 1997, 109.
(3) Lindquist, N.; Fenical, W.; Van Duyne, G. D.; Clardy, J. J. Am.
Chem. Soc. 1991, 113, 2303.
(4) Roesener, J. A.; Scheuer, P. J. J. Am. Chem. Soc. 1986, 108,
846.
(5) Jansen, R.; Kunze, B.; Reichenback, H.; Jurkiewicz, E.; Huns-
mann, G.; Höfle, G. Liebigs Ann. Chem. 1992, 357.
(6) Knight, D. W.; Pattenden, G.; Rippon, D. E. Synlett 1990, 36.
Martin, B. J.; Clough, J. M.; Pattenden, G.; Waldron, I. R.
Tetrahedron Lett. 1993, 34, 5151.
13C NMR (125.8 MHz; CDCl3): δ = 175.99 (s), 164.16 (s), 162.65 (s),
155.90 (s), 153.68 (s), 150.30 (s), 145.15 (d), 128. 40 (s), 124.54 (s),
113.33 (t), 59.53 (d), 54.84 (d), 54.84 (s), 47.00 (t), 31.50 (d), 30.60
(t), 29.68 (q), 27.14 (q), 24.98 (t), 19.19 (q), 17.71 (q), 12.03 (q),
11.75 (q).
Boden, C. D. J.; Pattenden, G. Tetrahedron Lett. 1994, 35, 8271.
Boden, C. D. J.; Pattenden, G. Tetrahedron Lett. 1995, 36, 6153.
Boyce, R. J.; Pattenden, G. Tetrahedron 1995, 51, 7313.
Boyce, R. J.; Mulqueen, G. C.; Pattenden, G. Tetrahedron 1995,
51, 7321.
Boden, C. D. J.; Norley, M. C.; Pattenden, G. Tetrahedron Lett.
1996, 37, 9111.
Chattopadhyay, S. K.; Pattenden, G. Synlett 1997, 1341 and
1345.
LRMS (CI, methane): m/z(%) = 445 (MH+, 84), 405 (21), 391 (8), 377
(100), 140 (61).
HRMS (CI, methane): m/z found MH+, 445.2446; C23H33O5N4 re-
quires 445.2450.
pyBOP13 (7.72 mg, 0.015 mmol) was added in one portion to a solu-
tion of the above prepared bis-oxazole acid (6.0 mg, 0.013 mmol), 3-
methylbut-2-en-1-ol (34 µL, 0.337 mmol) and Et3N (5.6 µL,
0.040 mmol) in CH2Cl2 (0.1 mL) at 0°C and under an atmosphere of
N2. The mixture was allowed to warm to r.t. and stirred for 24 h. The
solvents were removed by passing a stream of N2 over the surface to
leave a pale yellow residue. The residue was purified by column chro-
matography on silica gel using 40% EtOAc/light petroleum as eluant
to give muscoride A (1) (3.8 mg, 55%) as a colourless viscous oil;
[α]D –76.0 (c = 0.09, MeOH).
(7) Michael, J. P.; Pattenden, G. Angew. Chem., Int. Ed. Engl. 1993,
32, 1.
(8) Wipf, P.; Venkatraman, S. J. Org. Chem.,1996, 61, 6517.
(9) Tanaka, T.; Nakajima, K.; Okawa, K. Bull. Chem. Soc. Jpn.
1980, 53, 1352.
(10) Imada, Y.; Yuasa, M.; Nakamura, I.; Murahashi, S. J. Org.
Chem. 1994, 59, 2282.
(11) Atkins, G. M.; Burgess, E. M. J. Am. Chem. Soc. 1968, 90,
4744.
Wipf, P.; Miller, C. P. Tetrahedron. Lett. 1992, 33, 907.
(12) Videnov, G.; Kaiser, D.; Kempter, C.; Jung, G. Angew. Chem.,
Int. Ed. Engl. 1996, 35, 1503.
(13) Coste, J.; Le-Nguyen, D.; Castro, B. Tetrahedron Lett. 1990, 31,
205.
IR (film): ν = 3323, 2963, 1713, 1644, 1400, 1200, 1169, 1104, 1057
cm–1.
1H NMR (500 MHz; CDCl3): δ = 5.76 (1 H, dd, J = 17.6, 10.7 Hz,
CH=CH2), 5.47 [1 H, m, CH=C(CH3)2], 5.19 [1 H, dd, J = 7.3, 5.3
Hz, CH(oxazole)], 4.97 (1 H, dd, J = 17.6, 1.2 Hz, CH=CHH), 4.91
(1 H, dd, J = 10.7, 1.2 Hz, CH=CHH), 4.83 (1 H, d, J = 7.3 Hz,
(14) Lafargue, P.; Guenot, P.; Lellouche, J. Heterocycles 1995, 41,
947.