a yellow oil (440 mg, 87%). RF [3:2 petroleum ether:ethyl acetate] =
50%). RF [1:1 v/v petroleum ether/ethyl acetate] = 0.31; nmax.
=
=
0.53–0.43; nmax. (NaCl plate): 3034, 2988, 2952, 2910, 2848 (Ar C-
(ATR): 3477 (br acid O-H str), 1715, 1712 (C O, str), 1652 (C C)
cm-1; 1H NMR (400 MHz, CDCl3) d 1.43 (3H, d, J 6.8 Hz, CH3),
2.19–2.84 (4H, m, H-3ax, H-3eq, H-6ax, H-6eq), 2.97 (1H, d, J 1.8 Hz,
OH), 3.47 (1H, m, CH), 3.70 (3H, s, CO2Me), 3.73 (3H, s, CO2Me),
3.81 (1H, m, CH), 4.21 (1H, q, J 6.8 Hz, CH), 6.79 (1H, m, H-2);
13C NMR (100 MHz, CDCl3) d 18.6, 29.5, 32.7, 51.7, 52.1, 68.9,
73.9, 79.2, 127.8, 136.3, 166.7, 173.9.
-1
=
=
=
H stretch), 1730 (C O, str), 1657 (C C), 1454 (C C, Ar) cm ;
HRMS calcd for C19H22O7Na: MNa+, 385.1263. Found: MNa+,
385.1266.
The mixture of the above diastereoisomers (101 mg, 0.28 mmol),
N-bromosuccinimide (55 mg, 0.31 mmol) and AIBN (0.37 mg,
0.01 mmol) in anhydrous benzene (12 ml) was heated at reflux
(85 ◦C) for 2 h. The reaction was allowed to cool to 22 ◦C before
dilution with dichloromethane (15 ml). The reaction mixture was
washed with saturated sodium carbonate solution (25 ml), water
(25 ml), dried (MgSO4) and the solvent removed in vacuo to afford
the crude product as a pale yellow oil. Purification by column
chromatography (eluent: 3:1 v/v petroleum ether/ethyl acetate)
furnished the diastereomeric bromides 24 and 25 as colourless
oils. (44 mg, 36%, 18% (1S,2S,6R,7S)-diastereoisomer (24); 13%
(1S,2S,6R,7S)- diastereoisomer (25); 5% of an inseparable mixture
of 24 and 25, 31% yield over two steps).
(4R,5R,7S)-5-(1-Carboxy-ethoxy)-4-hydroxy-cyclohex-1-ene-
carboxylate 12. Diester 32 (26 mg, 0.10 mmol) was deprotected
using an identical procedure to that described for the synthesis
of 10 to afford the desired di-carboxylate 12 as a white solid
1
(0.30 mmol, quant., as determined by H NMR spectroscopic
studies using TSP as an internal standard). 1H NMR (400 MHz,
D2O) d 1.28 (3H, d, J 6.8 Hz, CH3), 2.09–2.70 (4H, m, H-3ax, H-3eq,
H-6ax, H-6eq), 3.42 (1H, ddd, J 5.6, 7.8, 16.1 Hz, CH), 3.74 (1H,
ddd, J 5.8, 8.0, 16.0 Hz, CH), 4.09 (1H, q, J 6.8 Hz, CH), 6.39 (1H,
m, H-2); 13C NMR (125 MHz, D2O) d 18.3, 29.4, 31.5, 68.1, 76.1,
77.8, 131.2, 132.4, 175.8, 182.1; HRMS calcd for C10H13O6K2:
MH+, 306.9981. Found: MH+, 306.9975.
24. 1H NMR (400 MHz, CDCl3) d 1.21 (3H, d, J 6.9 Hz, CH3),
2.68 (1H, dddd, J 2.7, 5.1, 7.8, 15.4 Hz, H-5ax), 3.02 (1H, dd, J
5.1 Hz, 18.2 Hz, H-5eq), 3.71 (3H, s CO2Me), 3.79 (3H, s, CO2Me),
3.79 (1H, m, H-6), 4.19 (1H, q, J 6.9 Hz, CH), 4.78 (1H, m, H-2),
5.68 (1H, dd, J 6.7, 8.4 Hz, H-1), 6.92 (1H, m, H-3), 7.46 (2H, m,
2 ¥ m-ArH), 7.59 (1H, m, p-ArH), 8.03 (2H, m, 2 ¥ o-ArH); 13C
NMR (100 MHz, CDCl3) d 18.9, 30.4, 45.2, 52.4, 52.7, 75.6, 76.0,
76.3, 129.0, 129.7, 130.0, 130.1, 133.9, 136.7, 165.5, 166.2, 173.9.
(1R,6R,7R)-Benzoic acid 4-methoxycarbonyl-6-(1-methoxycar-
bonyl-ethoxy)-cyclohex-3-enyl ester 29. Hydrodebromination of
25 (0.21 g, 0.47 mmol) was conducted in an identical manner to
that described for the synthesis of 19. The product was purified
by column chromatography (eluent: 3:1 v/v petroleum ether/ethyl
acetate) to afford the desired triester 29 as a pale yellow oil (0.10 g,
25. 1H NMR (400 MHz, CDCl3) d 1.33 (3H, d, J 6.8 Hz, CH3),
2.52 (1H, dddd, J 2.9, 5.2, 11.4, 17.6 Hz, H-5ax), 2.95 (1H, dd, J
5.2, 17.6 Hz, H-5eq), 3.41 (3H, s CO2Me), 3.79 (3H, s, CO2Me),
3.84 (1H, ddd, J 5.2, 8.8, 17.5 Hz, H-6), 4.15 (1H, q, J 6.8 Hz,
CH), 4.80 (1H, m, H-2), 5.68 (1H, dd, J 7.2, 9.1 Hz, H-1), 6.93
(1H, m, H-3), 7.46 (2H, m, 2 ¥ m-ArH), 7.57 (1H, m, p-ArH), 8.07
(2H, m, 2 ¥ o-ArH); 13C NMR (100 MHz, CDCl3) d 19.3, 29.5,
45.7, 52.1, 52.7, 74.2, 75.0, 76.3, 128.7, 129.1, 130.1, 130.2, 133.9,
136.7, 165.7, 166.2, 172.9.
59%). H NMR (400 MHz, CDCl3) d 1.37 (3H, d, J 6.8 Hz,
1
CH3), 2.39–2.92 (4H, m, H-2ax, H-2eq, H-5ax, H-5eq), 3.64 (3H, s,
CO2Me), 3.74 (3H, s, CO2Me), 3.92 (1H, dd, J H-6), 4.21 (1H, q,
J 6.8 Hz, CH), 5.35 (1H, dd, J 4.7, 10.6 Hz, H-1), 6.92 (1H, m,
H-3), 7.40 (2H, m, 2 ¥ m-ArH), 7.59 (1H, m, p-ArH), 8.03 (2H,
m, 2 ¥ o-ArH); 13C NMR (100 MHz, CDCl3) d 19.1, 27.0, 28.4,
51.7, 51.9, 68.8, 73.1, 73.8, 126.7, 128.3, 129.6, 130.0, 133.0, 136.0,
165.6, 167.0, 173.2.
(4R,5R,7R)-4-Hydroxy-5-(1-methoxycarbonyl-ethoxy)-cyclo-
hex-1-enecarboxylic acid methyl ester 33. Benzoyl ester depro-
tection of 29 (80 mg, 0.22 mmol) was conducted in an identical
manner to that described for the synthesis of 22. Purification by
column chromatography (eluent: 1:1 v/v petroleum ether/ethyl
acetate) gave the desired alcohol 33 as a colourless oil (20 mg,
35%). RF [1:1 v/v petroleum ether/ethyl acetate] = 0.36; 1H NMR
(400 MHz, CDCl3) d 1.43 (3H, d, J 6.9 Hz, CH3), 2.12–2.92 (4H,
m, H-3ax, H-3eq, H-6ax, H-6eq), 3.32 (1H, ddd, J 4.0, 9.5, 18.9 Hz,
CH), 3.71 (3H, s, CO2Me), 3.76 (3H, s, CO2Me), 3.79 (1H, m, CH),
4.10 (1H, s, OH), 4.18 (1H, q, J 6.9 Hz, CH), 6.81 (1H, m, H-2);
13C NMR (100 MHz, CDCl3) d 19.4, 29.6, 33.2, 51.8, 52.4, 68.9,
73.6, 80.5, 127.3, 137.0, 166.7, 174.7; HRMS calcd for C12H19O6:
MH+, 259.1182. Found: MH+, 259.1183.
(1R,6R,7S)-Benzoic acid 4-methoxycarbonyl-6-(1-methoxycar-
bonyl-ethoxy)-cyclohex-3-enyl ester 28. Hydrodebromination of
24 (0.20 g, 0.45 mmol) was conducted in an identical manner to
that described for the synthesis of 19. The product was purified by
column chromatography (eluent: 3:1 v/v petroleum ether/ethyl
acetate) to afford the desired triester 28 as a yellow oil (0.11 g,
-1
1
=
=
64%). nmax. (ATR): 1723, 1718 (C O, str), 1451 (C C Ar.) cm ; H
NMR (400 MHz, CDCl3) d 1.33 (3H, d, J 6.9 Hz, CH3), 2.38–2.90
(4H, m, H-2ax, H-2eq, H-5ax, H-5eq), 3.70 (3H, s, CO2Me), 3.74 (3H,
s, CO2Me), 3.87 (1H, m, H-6), 4.28 (1H, q, J 6.8 Hz, CH), 5.29
(1H, ddd, J 5.3, 6.9, 12.3 Hz, H-1), 6.88 (1H, m, H-3), 7.42 (2H,
m, 2 ¥ m-ArH), 7.57 (1H, m, p-ArH), 7.98 (2H, m, 2 ¥ o-ArH); 13
C
NMR (100 MHz, CDCl3) d 19.1, 28.1, 29.4, 51.9, 52.2, 70.0, 74.5,
75.3, 127.7, 128.6, 129.7, 130.0, 133.4, 135.3, 165.9, 167.0, 173.9;
HRMS calcd for C19H22O7Na: MNa+, 385.1263. Found: MNa+,
385.1274.
(4R,5R,7R)-5-(1-Carboxy-ethoxy)-4-hydroxy-cyclohex-1-ene-
carboxylate 13. Diester 33 (14 mg, 0.05 mmol) was deprotected
using an identical procedure to that described for the synthesis
of 10 to afford the desired di-carboxylate 13 as a white solid
(4R,5R,7S)-4-Hydroxy-5-(1-methoxycarbonyl-ethoxy)-cyclo-
hex-1-enecarboxylic acid methyl ester 32. Benzoyl ester depro-
tection of 28 (95 mg, 0.26 mmol) was conducted in an identical
manner to that described for the synthesis of 22. Purification by
column chromatography (eluent: 1:1 v/v petroleum ether/ethyl
acetate) gave the desired alcohol 32 as a colourless oil (34 mg,
1
(0.05 mmol, quant., as determined by H NMR spectroscopic
studies using TSP as an internal standard). nmax. (ATR): 3329 (br
-1
1
=
=
acid O-H str), 1657, 1604 (C O, str), 1553 (C C) cm ; H NMR
(400 MHz, D2O) d 1.29 (3H, d, J 6.9 Hz, CH3), 2.03–2.75 (4H,
m, H-3ax, H-3eq, H-6ax, H-6eq), 3.47 (1H, ddd, J 5.6, 8.3, 17.1 Hz,
This journal is The Royal Society of Chemistry 2009
Org. Biomol. Chem., 2009, 7, 2421–2429 | 2427
©