Two Analogues of Showdomycin
91
subjected to flash chromatography (silica, 10 : 2 : 1 v/v/v ethyl acetate–
MeOH–H2O elution). Concentration of the appropriate fractions (RF
0.4) then afforded the title maleimide 2 (8 mg, 44%) as a clear, colour-
less oil, [α]D + 9◦ (c 0.8 in MeOH) (Found: M−, 259.0685. C10H13NO7
requires M−, 259.0692). νmax/cm−1 3325, 2914, 2846, 1717, 1588,
1408, 1354, 1087. δH (300 MHz, CD3OD/CD3CN) 6.68 (1 H, d, J 0.9),
4.18 (1 H, dd, J 0.9 and 9.2), 3.84 (1 H, dd, J 2.1 and 8.7), 3.68 (1 H,
m), 3.49–3.20 (4 H, complex m). δC (75 MHz, CD3OD/CD3CN) 174.9,
173.2, 148.5, 131.7, 82.5, 79.4, 75.3, 74.5, 71.5, 62.8. m/z (negative-ion
ESI) 259 (M−).
standunderH2 (1 atm)at18◦Cfor16 h, andthenfilteredthroughapadof
Celite.The solids thus retained were washed with EtOH (approx. 20 mL)
and the combined filtrates concentrated under reduced pressure to give
a grey solid. This material was dissolved in CH2Cl2 (10 mL) and the
resultingsolutionwashedwithwater(2 × 10 mL)andbrine(1 × 10 mL).
Subsequent drying of the separated organic phase (MgSO4) and evapo-
ration of the solvent afforded cyclohexane 17 (94 mg, 81%) as a clear,
colourless oil, [α]D −89◦ (c 1.1 in CHCl3) (Found: M+•, 435.2803.
C24H41NO4Si requires M+•, 435.2805). νmax/cm−1 2944, 2869, 1740,
1479, 1464, 1368, 1241, 1154, 1094, 1048, 884, 865, 779, 691, 661. δH
(300 MHz) 6.64 (1 H, t, J 2.7, Ar–H), 6.51 (1 H, t, J 1.5, Ar–H), 6.13
(1 H, dd, J 1.5 and 2.7, Ar–H), 5.11 (1 H, dd, J 8.1 and 11.4), 4.37 (1
H, m), 4.00 (1 H, dd, J 5.1 and 8.1), 2.51 (1 H, dt, J 3.3 and 11.6), 2.21
(1 H, broadened d, J 12.4), 1.83 (3 H, s, CH3), 1.82 (3 H, m), 1.60 (3
H, s, CH3), 1.39 (3 H, m, CHMe2), 1.38 (3 H, s, CH3), 1.07 (12 H,
s, 4 CH3), 1.05 (6 H, s, 2 CH3). δC (75 MHz) 169.7 (C=O), 125.4,
123.8, 120.8, 109.7, 108.9, 79.4 (C–O), 77.3 (C–O), 74.7 (C–O), 39.0,
27.9, 27.8 (CH2), 26.5, 26.4 (CH2), 21.0, 17.8(0), 17.7(8), 11.6. m/z
(EI, 70 eV) 435 (M+•, 14%), 375 (76), 289 (100), 247 (43), 173 (72),
105 (36).
(3aS,4R,5R,7aS)-7-Bromo-3a,4,5,7a-tetrahydro-5-
[1-(triisopropylsilyl)-1H-pyrrol-3-yl]-2,2-dimethyl-
benzo[d][1,3]dioxol-4-ol 15
N-TIPS-pyrrole (7)[8] (230 mg, 2.5 mol equiv.) was added in one
portion to a mixture of epoxide 14[12] (102 mg, 0.41 mmol) and InCl3
(9 mg, 0.04 mmol, 10 mol%) in CH2Cl2 (15 mL). The ensuing mixture
was stirred at 18◦C for 5 days then filtered through a pad of type-60
silica gel. The filtrate was concentrated under reduced pressure to give a
yellow oil which was subjected to flash chromatography (silica, 1 : 4 v/v
ethyl acetate–hexane elution). Collection of the appropriate fractions
(RF 0.2) afforded compound 15 (102 mg, 54%) as a clear, colourless oil
(Found: M+•, 471.1628. C22H36 81BrNO3Si requires M+•, 471.1627).
νmax/cm−1 3471, 2942, 2862, 1476, 1461, 1378, 1277, 1215, 1161,
1096, 1071, 1013, 879, 869, 789, 655. δH (300 MHz) 6.77 (1 H, t, J 2.1,
Ar–H), 6.66 (1 H, t, J 1.5, Ar–H), 6.26 (1 H, d, J 2.1, H6), 6.19 (1 H, dd,
J 1.5 and 2.1, Ar–H), 4.77 (1 H, dd, J 0.9 and 6.4, H7a), 4.21 (1 H, dd, J
6.7 and 9.1), 3.54 (1 H, t, J 9.4), 3.26 (1 H, dt, J 1.5 and 9.7), 2.14 (1 H, d,
J 1.5, OH), 1.57 (3 H, s, CH3), 1.45 (3 H, s, CH3), 1.43 (3 H, m, SiCH),
1.08 (18 H, d, J 7.3, CH3). δC (75 MHz) 136.9, 125.7, 123.2, 122.4,
117.5, 110.3 [C(CH3)2], 109.7, 79.2 (C–O), 77.8 (C–O), 73.9 (C–O),
43.0, 28.4 (CH3), 26.0 (CH3), 18.0 (CH3), 11.9 (SiCH). m/z (EI, 70 eV)
471 and 469 (M+•, 17 and 16%), 269 (87), 267 (67), 223 (59), 180
(100), 128 (52), 110 (48), 75 (39). This compound discolours rapidly
and was used immediately in the next step of the reaction sequence.
(3aR,4R,5R,7aR)-Hexahydro-2,2-dimethyl-5-(1H-pyrrol-
3-yl)benzo[d][1,3]dioxol-4-yl acetate 18
N-TIPS-protected pyrrole 17 (94 mg, 0.22 mmol) was dissolved in
freshly distilled THF (10 mL) and the resulting solution cooled to 0◦C
(ice bath). TBAF (216 µL of a 1.0 M solution in THF, 0.22 mmol) was
then added dropwise. After the addition was complete stirring was
continued at 0◦C for 1 h then the reaction mixture was diluted with
CH2Cl2 (10 mL) and washed with water (1 × 10 mL). The separated
aqueous phase was extracted with CH2Cl2 (3 × 10 mL) and the com-
bined organic phases were washed with brine (1 × 20 mL) before being
dried (MgSO4), filtered, and concentrated under reduced pressure. The
resulting clear, colourless oil was subject to flash chromatography (sil-
ica, 1 : 1 v/v ethyl acetate–hexane elution). Collection of the appropriate
fractions (RF 0.6) then afforded compound 18 (48 mg, 80%) as a clear,
colourless oil, [α]D −40◦ (c 1.3 in CHCl3) (Found: M+•, 279.1483.
C15H21NO4 requires M+•, 279.1471). νmax/cm−1 3392, 2984, 2936,
2874, 1732, 1454, 1434, 1378, 1244, 1220, 1153, 1099, 1043, 865, 793,
665. δH (300 MHz) 8.22 (1 H, br s, NH), 6.65 (1 H, q, J 2.4, Ar–H),
6.55 (1 H, q, J 1.8, Ar–H), 6.05 (1 H, q, J 1.8, Ar–H), 5.06 (1 H, dd, J
8.1 and 11.4), 4.38 (1 H, m), 4.02 (1 H, dd, J 4.8 and 8.1), 2.53 (1 H,
dt, J 2.7 and 11.4), 2.23 (1 H, br d, J 11.4), 1.88 (3 H, s, CH3), 1.85
(3 H, m), 1.58 (3 H, s, CH3), 1.38 (3 H, s, CH3). δC (75 MHz) 170.1
(C=O), 123.6, 117.4, 114.7, 109.0, 107.8, 79.2 (C–O), 77.7 (C–O), 74.6
(C–O), 38.9, 27.9, 27.2 (CH2), 26.5, 26.4 (CH2), 21.1. m/z (EI, 70 eV)
279 (M+•, 4%), 264 (4), 219 (41), 161 (26), 144 (54), 133 (100), 132
(37), 118 (16), 106 (21), 93 (24), 80 (23), 67 (16).
(3aS,4R,5R,7aS)-7-Bromo-3a,4,5,7a-tetrahydro-5-
[(1-(triisopropylsilyl)-1H-pyrrol-3-yl)]-2,2-dimethyl-
benzo[d][1,3]dioxol-4-yl acetate 16
Pyrrole 15 (60 mg, 0.13 mmol) was dissolved in dry CH2Cl2 (3 mL)
and Et3N (0.45 mL, 3.2 mmol) was added under a nitrogen atmosphere.
The ensuing mixture was cooled to 0◦C (ice/water bath) and Ac2O
(241 µL, 2.56 mmol) was added dropwise with a syringe.After the addi-
tion was complete, the reaction mixture was allowed to warm to 18◦C,
stirring was continued at this temperature for 48 h, then it was recooled
to 0◦C and MeOH (0.6 mL) added. The resulting mixture was washed
with water (2 × 5 mL) and brine (1 × 5 mL) then dried (MgSO4), fil-
tered, and concentrated under reduced pressure to afford a light-brown
oil.This material was subjected to flash chromatography (silica, 1 : 4 v/v
ethyl acetate–hexane elution). Collection of the appropriate fractions
(RF 0.4) afforded acetate 16 (41 mg, 63%) as a clear, colourless oil,
[α]D + 2◦ (c 1.2 in CHCl3). νmax/cm−1 2947, 2869, 2603, 2497, 1747
(C=O), 1640, 1563, 1480, 1464, 1373, 1227, 1167, 1078, 1017, 883,
870, 792, 692, 659, 580. δH (300 MHz) 6.66 (1 H, t, J 2.4, Ar–H), 6.56
(1 H, t, J 1.5, Ar–H), 6.30 (1 H, d, J 2.1, H6), 6.14 (1 H, dd, J 1.5 and
2.4, Ar–H), 5.16 (1 H, t, J 9.6), 4.73 (1 H, dd, J 1.5 and 6.0), 4.24 (1
H, dd, J 6.0 and 9.6), 3.43 (1 H, dt, J 1.5 and 9.6), 1.90 (3 H, s, OAc),
1.55 (3 H, s, CH3), 1.41 (3 H, s, CH3), 1.39 (3 H, m, SiCH), 1.05 (18 H,
d, J 7.5, CH3). δC (75 MHz) 169.4 (C=O), 136.9, 124.5, 122.6, 121.6,
116.6, 110.1, 110.0, 77.7 (C–O), 77.2 (C–O), 73.1 (C–O), 40.8 (C5),
27.8 (CH3), 26.3 (CH3), 20.9 (CH3), 17.7(4) (CH3), 17.7(1) (CH3), 11.6
(SiC). m/z (ESI) 534 and 536 [(M + Na)+, 95 and 100%].
(3aR,4R,5R,7aR)-Hexahydro-5-(2,5-dioxo-2,5-dihydro-1H-pyrrol-
3-yl)-2,2-dimethylbenzo[d][1,3]dioxol-4-yl acetate 19
A magnetically stirred solution of pyrrole 18 (47 mg, 0.17 mmol)
in CH2Cl2 (12 mL) was treated with molecular sieves (150 mg, 4 Å,
powdered) then PCC (181 mg, 0.84 mmol, 4.9 mol equiv.). The ensuing
mixture was stirred at 18◦C for 16 h then diluted with CH2Cl2 (10 mL),
and filtered through a pad of type-60 silica gel. The solids thus retained
were washed with CH2Cl2 (10 mL) and ethyl acetate (10 mL) and the
combined filtrates concentrated under reduced pressure to give a brown
solid. This material was subjected to flash chromatography (silica,
1 : 1 v/v ethyl acetate–hexane elution) and collection of the appropri-
ate fractions (RF 0.35) afforded the title compound 19 (43 mg, 83%)
•
as a clear, colourless oil, [α]D −23◦ (c 0.35 in CHCl3) (Found: M+
,
309.1218. C15H19NO6 requires M+•, 309.1212). νmax/cm−1 3271,
2986, 2933, 1722, 1631, 1455, 1436, 1372, 1350, 1242, 1154, 1098,
1048, 1004, 936, 865, 788, 736, 675. δH (300 MHz) 8.04 (1 H, br s,
NH), 6.37 (1 H, s), 5.20 (1 H, dd, J 7.5 and 11.4), 4.39 (1 H, m), 4.03
(1 H, dd, J 4.8 and 7.5), 2.68 (1 H, t, J 9.5), 2.22 (1 H, d, J 7.5), 2.02
(3 H, s, CH3), 1.81 (3 H, m), 1.57 (3 H, s, CH3), 1.38 (3 H, s, CH3).
δC (75 MHz) 170.8 (C=O), 170.4 (C=O), 170.1 (C=O), 149.4, 127.5,
109.3, 78.2(C–O), 74.4(C–O), 73.9(C–O), 36.9, 27.7, 26.2, 25.6(CH2),
(3aR,4R,5R,7aR)-Hexahydro-5-[1-(triisopropylsilyl)-1H-pyrrol-
3-yl]-2,2-dimethylbenzo[d][1,3]dioxol-4-yl acetate 17
Compound 16 (136 mg, 0.27 mmol) was dissolved in EtOH (8 mL)
containing Et3N (185 µL, 1.32 mmol, 4.9 mol equiv.). The resulting
solution was treated with 10% palladium on charcoal (45 mg), allowed to