Job/Unit: O43000
/KAP1
Date: 25-08-14 11:34:44
Pages: 16
M. A. Brimble et al.
FULL PAPER
(2ϫC), 133.07* (C), 133.04* (C), 129.82* (CH), 129.79* (CH), 18.0 Hz, 1 H), 5.29 (d, J = 18.0 Hz, 1 H), 4.59 (s, 2 H), 4.42–4.40
129.76 (CH), 129.73 (CH), 127.7 (4ϫCH), 109.2* (C), 108.7 (C), (m, 1 H), 3.89–3.87 (m, 1 H), 3.83–3.75 (m, 2 H), 2.80–2.78 (m, 2
81.4* (CH), 80.8 (CH), 78.0* (CH), 76.0 (CH), 71.7* (CH), 69.6 H), 1.41 (s, 3 H), 1.38 (s, 3 H), 1.05 (s, 9 H), 0.87 (s, 9 H), 0.04 (s,
(CH), 64.0 (CH2), 63.8* (CH2), 47.7 (CH2), 37.7* (CH2), 37.4
3 H), 0.03 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 201.7
(CH2), 27.34 (CH3), 27.26* (CH3), 26.95* (CH3), 27.0 (CH3), 26.8 (C), 179.7 (CH), 142.0 (C), 135.6 (4ϫCH), 133.04 (C), 133.00 (C),
(3ϫCH ), 19.2 (C) ppm. IR (neat): ν = 3452, 2930, 2857, 1674,
132.3 (C), 129.74 (CH), 129.71 (CH), 127.7 (4ϫCH), 123.9 (CH),
110.0 (CH), 109.2 (C), 80.8 (CH), 74.2 (CH), 63.7 (CH2), 57.2
(CH2), 55.4 (CH2), 43.9 (CH2), 27.2 (CH3), 26.9 (CH3) 26.8
(3ϫCH3), 25.8 (3ϫCH3), 19.1 (C), 18.2 (C), –5.4 (2ϫCH3) ppm.
˜
3
1427, 1295, 1145, 1112, 942, 858, 824, 704, 613 cm–1. HRMS
(ESI+): m/z 444.2525 [M + H]+ (calcd. for C25H38NO4Si 444.2565).
Maillard Condensation Product 35: A solution of amine 34 (0.027 g,
0.61 mmol) in undistilled 1,4-dioxane (1 mL) was added dropwise
to a solution of dihydropyranone 12 (0.060 g, 0.23 mmol) and tri-
ethylamine (0.05 mL, 0.36 mmol) in undistilled 1,4-dioxane (1 mL)
over 5 min at room temp. The mixture was allowed to stir at room
temp. for 2 h, then concentrated in vacuo to give the crude material.
The crude was purified via flash column chromatography (silica
gel, ethyl acetate/hexanes, 1:8 as eluent) to give the product as the
two separable diastereomers 35a (0.018 g, 21%) and 35b (0.028 g,
33%) as colourless oils.
IR (neat): ν = 3674, 2929, 2856, 1765, 1670, 1462, 1427, 1362, 1251,
˜
1216, 1112, 1076, 836, 702 cm–1. HRMS (CI): m/z 686.3471 [M +
Na]+ (calcd. for C37H53NNaO6Si2 686.3304).
TBDPS-Spiroketal 39: HCl (4 m in 1,4-dioxane, 1.0 mL,
4.00 mmol) was added to a solution of crude ketone 37 (0.027 g,
0.041 mmol) in THF/water (1:1, 2 mL), and the mixture allowed to
stir at room temp. for 2.5 h. The reaction was neutralised with satd.
aq. NaHCO3 to pH 7, and the mixture extracted with ethyl acetate
(3ϫ10 mL). The combined organic extracts were dried with
MgSO4 and concentrated in vacuo to give the crude material. The
crude was purified via flash column chromatography (silica gel,
ethyl acetate/hexanes, 1:3 as eluent) to give 39 (0.012 g, 61%, dr
3.4:1) as a yellow oil and an inseparable mixture of two dia-
stereomers. 1H NMR (400 MHz, CDCl3, * denotes minor isomer):
δ = 9.47 (s, 1 H), 9.45* (s, 1 H), 7.67–7.62 (m, 4 H), 7.43–7.35 (m,
6 H), 6.93* (d, J = 4.0 Hz, 1 H), 6.92 (d, J = 4.0 Hz, 1 H), 5.99 (d,
J = 4.0 Hz, 1 H), 5.97* (d, J = 4.0 Hz, 1 H), 5.13–3.70 (m, 8 H),
3.03 (d, J = 7.2 Hz, 1 H), 2.79* (d, J = 7.2 Hz, 1 H), 2.57 (dd, J =
13.9, 6.6 Hz, 1 H), 2.38* (d, J = 14.0 Hz, 1 H), 2.25* (dd, J = 13.9,
5.2 Hz, 1 H), 2.14 (dd, J = 13.9, 3.9 Hz, 1 H), 1.04 (s, 9 H) ppm.
13C NMR (100 MHz, CDCl3, * denotes minor isomer): δ = 179.8*
(CH), 178.6 (CH), 135.6 (4ϫCH), 135.54* (4ϫCH), 135.46*
(2ϫCH), 134.7 (C), 134.6 (C), 133.04* (C), 133.00* (C), 132.6 (C),
132.1 (C), 131.2 (C), 131.1* (C), 129.98 (CH), 129.96 (CH), 129.8*
(2ϫCH), 127.84* (2ϫCH), 127.76 (2ϫCH), 124.1* (CH), 123.9
(CH), 104.8* (CH), 104.6 (CH), 103.5* (C), 102.3 (C), 85.6* (CH),
80.8 (CH), 72.6 (CH), 72.0* (CH), 63.0* (CH2), 62.8 (CH2), 58.5
(CH2), 58.2* (CH2), 51.4 (CH2), 51.0* (CH2), 46.3 (CH2), 44.6*
(CH2), 26.78* (3ϫCH3), 26.73 (3ϫCH3), 19.14* (C), 19.07 (C)
1
35a: [α]2D0 = –10.0 (c = 0.8, CHCl3). H NMR (400 MHz, CDCl3):
δ = 9.47 (s, 1 H), 7.71–7.67 (m, 4 H), 7.42–7.37 (m, 6 H), 6.90 (d,
J = 4.0 Hz, 1 H), 6.19 (d, J = 4.0 Hz, 1 H), 4.78 (d, J = 12.0 Hz,
1 H), 4.71 (d, J = 12.0 Hz, 1 H), 4.58 (dd, J = 13.2, 2.4 Hz, 1 H),
4.31–4.27 (m, 1 H), 4.26–4.20 (m, 1 H), 4.19–4.12 (m, 1 H), 3.84–
3.70 (m, 3 H), 3.20 (d, J = 4.0 Hz, 1 H), 1.85–1.81 (m, 2 H), 1.41
(s, 3 H), 1.37 (s, 3 H), 1.06 (s, 9 H), 0.90 (s, 9 H), 0.10 (s, 3 H),
0.08 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 179.9 (CH),
142.6 (C), 135.6 (4ϫCH), 133.14 (C), 133.09 (C), 132.7 (C), 129.74
(CH), 129.71 (CH), 127.7 (4ϫCH), 124.9 (CH), 110.3 (CH), 108.0
(C), 77.6 (CH), 73.9 (CH), 69.8 (CH), 62.6 (CH2), 57.4 (CH2), 51.8
(CH2), 34.6 (CH2), 28.1 (CH3), 26.9 (CH3), 25.8 (3ϫCH3), 25.6
(3ϫCH ), 19.2 (C), 18.3 (C), –5.3 (2ϫCH ) ppm. IR (neat): ν =
˜
3
3
3671, 3465, 2956, 2930, 2857, 1739, 1660, 1462, 1428, 1137, 1250,
1112, 1073, 837, 779, 703, 613 cm–1. HRMS (CI): m/z 688.3379 [M
+ Na]+ (calcd. for C37H55NNaO6Si2 688.3462).
35b: [α]2D0 = –7.0 (c = 1.4, CHCl3). 1H NMR (400 MHz, CDCl3): δ
= 9.47 (s, 1 H), 7.69–7.65 (m, 4 H), 7.43–7.37 (m, 6 H), 6.89 (d, J
= 4.0 Hz, 1 H), 6.19 (d, J = 4.0 Hz, 1 H), 4.83 (d, J = 12.0 Hz, 1
H), 4.72 (d, J = 16.0 Hz, 1 H), 4.58 (dd, J = 14.0, 2.4 Hz, 1 H),
4.31–4.28 (m, 1 H), 4.22 (d, J = 12.0 Hz, 1 H), 4.19–4.12 (m, 1 H),
3.81–3.74 (m, 3 H), 3.47 (d, J = 2.4 Hz, 1 H), 1.96–1.92 (m, 1 H),
1.74–1.66 (m, 1 H), 1.44 (s, 3 H), 1.36 (s, 3 H), 1.04 (s, 9 H), 0.91
(s, 9 H), 0.10 (s, 3 H), 0.07 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 179.5 (CH), 143.3 (C), 135.6 (4ϫCH), 133.14 (C),
133.09 (C), 132.6 (C), 129.74 (CH), 129.71 (CH), 127.7 (4ϫCH),
124.9 (CH), 109.9 (CH), 108.5 (C), 77.8 (CH), 77.3 (CH), 71.9
(CH), 62.5 (CH2), 57.7 (CH2), 51.4 (CH2), 33.6 (CH2), 27.9 (CH3),
26.9 (3ϫCH3), 25.8 (3ϫCH3), 25.5 (CH3), 19.2 (C), 18.3 (C),
ppm. IR (neat): ν = 3674, 2929, 2856, 1765, 1670, 1462, 1427, 1362,
˜
1251, 1216, 1112, 1076, 836, 702 cm–1. HRMS (ESI+): m/z 514.2003
[M + Na]+ (calcd. for C28H33NNaO5Si 514.2020).
Spiroketals 40a and 40b: TBAF (1 m in THF, 0.1 mL, 0.10 mmol)
was added to a solution of spiroketal 37 (6 mg, 0.012 mmol) in
THF (0.5 mL), and the mixture allowed to stir at room temp. for
2 h. The mixture was then concentrated in vacuo to remove most
of the solvent and filtered through a pad of silica. The filter cake
was washed with ethyl acetate (10 mL), and the combined filtrates
concentrated in vacuo to give the crude material. The crude was
purified via preparative TLC (ethyl acetate/hexanes, 5:1 as eluent)
to give 40a (0.9 mg, 30%) and 40b (1.5 mg, 50%) as yellow oils.
–5.30 (CH ), –5.33 (CH ) ppm. IR (neat): ν = 3671, 3465, 2956,
˜
3
3
2930, 2857, 1739, 1660, 1462, 1428, 1137, 1250, 1112, 1073, 837,
779, 703, 613 cm–1. HRMS (CI): m/z 688.3379 [M + Na]+ (calcd.
for C37H55NNaO6Si2 688.3460).
1
40a: H NMR (400 MHz, CD3COCD3): δ = 9.47 (s, 1 H), 6.98 (d,
J = 4.0 Hz, 1 H), 6.04 (d, J = 4.0 Hz, 1 H), 4.94 (d, J = 15.5 Hz,
1 H), 4.81 (d, J = 15.5 Hz, 1 H), 4.69 (d, J = 14.0 Hz, 1 H), 4.61–
4.56 (m, 1 H), 4.23 (d, J = 13.9 Hz, 1 H), 4.14 (ddd, J = 5.1, 9.8,
9.8 Hz, 1 H), 3.87–3.75 (m, 2 H), 2.53 (dd, J = 6.6, 14.6 Hz, 1
H), 2.12 (dd, J = 3.3, 14.1 Hz, 1 H) ppm. 13C NMR (100 MHz,
CD3COCD3): δ = 179.0 (CH), 135.8 (C), 132.3 (C), 124.2 (CH),
105.3 (CH), 103.1 (C), 84.0 (CH), 72.1 (CH), 61.5 (CH2), 58.8
Ketopyrrole 37: NMO (3.9 mg, 0.33 mmol) and TPAP (1 mg,
0.002 mmol) were added to a mixture of alcohols 35a and 35b
(0.030 g, 0.045 mmol) and activated molecular sieves (4 Å) (0.010 g)
in dichloromethane (2 mL). The mixture was allowed to stir at
room temp. for 0.5 h, then filtered through a plug of silica. The
filter cake was further washed with THF (3ϫ10 mL), and the com-
bined filtrates concentrated in vacuo to give the crude 37 (0.029 g,
97%) as a pale brown oil that was carried forward without further
(CH ), 52.4 (CH ), 47.5 (CH ) ppm. IR (neat): ν = 3321, 2929,
˜
2
2
2
2845, 1725, 1410, 1251, 1051, 788 cm–1. HRMS (ESI+): m/z
276.0848 [M + Na]+ (calcd. for C12H15NNaO5 276.0842).
1
purification. [α]2D0 = +16.0 (c = 0.2, CHCl3). H NMR (400 MHz,
CDCl3): δ = 9.44 (s, 1 H), 7.70–7.66 (m, 4 H), 7.43–7.36 (m, 6 H),
40b: [α]2D4 = –121.3 (c = 0.08, MeOH). 1H NMR (400 MHz,
6.89 (d, J = 4.0 Hz, 1 H), 6.19 (d, J = 4.0 Hz, 1 H), 5.40 (d, J = CD3COCD3): δ = 9.47 (s, 1 H), 6.98 (d, J = 4.0 Hz, 1 H), 6.04 (d,
12
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0