M. A. Brimble et al.
FULL PAPER
10 mL) and the combined organic extracts were washed with brine
(10 mL), dried with Na2SO4, and concentrated in vacuo. Purifica-
tion by flash chromatography (hexanes/EtOAc, 4:1) afforded the
H), 1.14 (d, J = 6.7 Hz, 3 H), 0.89 (s, 9 H), 0.10 (s, 3 H), 0.07 (s,
3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 178.7 (2 C), 142.8,
126.0, 117.1, 110.5, 80.3, 62.7, 57.4, 43.5, 29.7, 25.8 (3 C), 18.5,
title compounds (0.27 g, 1.2 mmol, 81%) as a yellow oil. 1H NMR 15.0, –5.1, –5.3 ppm. HRMS (ESI+): calcd. for C18H30NO4Si+
(400 MHz, CDCl3): δ = 6.78 (m, 4 H), 6.69 (m, 4 H), 4.74–4.67 (m, [M + H]+ 352.1939; found 352.1942.
1 H), 4.16–4.09 (m, 1 H), 3.82 (d, J = 10.4 Hz, 1 H), 3.81 (d, J =
Compound 25a: [α]1D9 = –25 (c = 0.1, CHCl ). IR (neat): ν
=
max
˜
3
11.6 Hz, 1 H), 3.74 (s, 6 H), 2.58–2.48 (m, 1 H), 2.04–1.97 (m, 1
H), 1.43 (d, J = 6.1 Hz, 3 H), 1.33 (d, J = 6.8 Hz, 3 H), 1.24 (d, J
= 6.6 Hz, 3 H), 1.18 (d, J = 6.1 Hz, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 176.2, 176.0, 152.8, 152.7, 140.7 (2 C),
115.4 (2 C), 115.3 (2 C), 114.6 (4 C), 79.4, 77.1, 61.7, 59.1, 55.4,
45.9, 40.1, 18.2, 15.5, 14.1, 12.5 ppm.
2920, 2850, 1779, 1664, 1450, 1253, 1180, 1116, 1050, 835,
1
776 cm–1. H NMR (400 MHz, CDCl3): δ = 7.96 (s, 1 H), 6.59 (d,
J = 3.8 Hz, 1 H), 6.14 (d, J = 3.9 Hz, 1 H), 5.02 (d, J = 11.6 Hz,
1 H), 4.68 (d, J = 3.9 Hz, 2 H), 4.17–4.11 (m, 2 H), 3.58 (d, J =
10.9 Hz, 1 H), 3.23–3.16 (m, 1 H), 2.55–2.45 (m, 1 H), 1.47 (d, J
= 6.2 Hz, 3 H), 1.44 (d, J = 6.1 Hz, 3 H), 1.10 (m, 6 H), 0.88 (s, 9
H), 0.09 (s, 3 H), 0.05 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 175.0, 172.2, 155.3, 139.6, 129.9, 120.4, 109.8, 80.8, 80.5, 76.2,
62.9, 57.6, 46.2, 42.7, 29.7, 25.8 (3 C), 18.8, 18.2, 14.8, 13.8, –5.1,
–5.3 ppm. HRMS (ESI+): calcd. for C24H39N2O5Si+ [M + H]+
463.2623; found 463.2615.
General Procedure A: Oxidative Cleavage: To a solution of lactone
(1 equiv.) in MeCN (2 m with respect to the lactone) at 0 °C was
added dropwise a solution of CAN (3 equiv.) in H2O (0.3 m with
respect to the lactone). The reaction mixture was stirred at 0 °C for
1 h then washed with EtOAc. The aqueous layer was made slightly
basic (pH 8) by the addition of satd. aq. NaHCO3 and the inor-
ganic solids were filtered through a sintered funnel. The filtrate
was extracted with EtOAc followed by CHCl3/iPrOH (4:1). The
combined organic extracts were dried with Na2SO4 and concen-
trated in vacuo to afford the crude product, which was purified by
flash chromatography (hexanes/EtOAc, 1:4 then to CH2Cl2/MeOH,
95:5).
TBS-Protected Funebral (24a): Following general procedure B, re-
action of a mixture of amino lactones 11a and 11b (16 mg,
123 μmol) provided the title compound 24a (4 mg, 12 μmol, 37%)
along with an inseparable mixture of 24b, 25a and 25b (4 mg, 41%)
as pale-yellow oils.
(–)-Funebral (3): To a solution of silyl ether 24a (9 mg, 26 μmol) in
THF (0.2 mL) was added 3HF·Et3N (8 drops) and the reaction
mixture was stirred at room temp. for 2 h. Satd. aq. NaHCO3
(1 mL) was added and the aqueous layer was extracted with EtOAc
(3ϫ 3 mL). The combined organic extracts were dried with
Na2SO4, filtered, and concentrated in vacuo. Purification by pre-
parative thin-layer chromatography (hexanes/EtOAc, 1:1) afforded
the title compound 3 (5.2 mg, 22 μmol, 86%) as a colorless oil.
[α]1D9 = –33 (c = 0.4, MeOH); ref.[10] [α]D = –36.1 (c = 1.0, MeOH).
1H NMR (400 MHz, CDCl3): δ = 9.40 (s, 1 H), 7.00 (d, J = 4.0 Hz,
1 H), 6.26 (d, J = 4.0 Hz, 1 H), 5.05 (d, J = 11.4 Hz, 1 H), 4.67 (d,
J = 13.7 Hz, 1 H), 4.60 (d, J = 13.7 Hz, 1 H), 4.29–4.24 (m, 1 H),
2.76–2.68 (m, 1 H), 1.59 (d, J = 6.2 Hz, 3 H), 1.12 (d, J = 6.6 Hz,
3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 178.9, 172.1, 142.6,
(3S,4S,5R)-3-Amino-4,5-dimethyltetrahydro-2-furanone (11a): Fol-
lowing general procedure A, reaction with lactone 23a (0.1 g,
425 μmol) provided the title compound 11 (19 mg, 145 μmol, 34%)
1
as a yellow oil. [α]1D9 = –18 (c = 1.3, CHCl3). H NMR (400 MHz,
CDCl3): δ = 4.06–3.99 (m, 1 H), 3.24 (d, J = 11.6 Hz, 1 H), 2.17
(br. s, 2 H), 1.83–1.72 (m, 1 H), 1.40 (d, J = 6.1 Hz, 3 H), 1.18 (d,
J = 6.5 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 178.0,
79.7, 58.7, 47.3, 18.4, 14.0 ppm. The 1H NMR data closely matched
those previously reported.[10]
(3S,4S,5R)- and (3S,4S,5S)-3-Amino-4,5-dimethyltetrahydro-2-fur-
anone (11a and 11b): Following general procedure A, reaction of
lactones 23a and 23b (0.1 g, 425 μmol) provided the title com-
pounds 11a and 11b (19 mg, 145 μmol, 34%) as a yellow oil. 1H
NMR (400 MHz, CDCl3): δ = 4.68–4.61 (m, 1 H), 4.06–3.99 (m, 1
H), 3.27 (d, J = 11.4 Hz, 1 H), 3.22 (d, J = 11.6 Hz, 1 H), 2.32–
2.25 (m, 1 H), 1.81–1.71 (m, 1 H), 1.39 (d, J = 6.3 Hz, 3 H), 1.24
(d, J = 6.8 Hz, 3 H), 1.18 (d, J = 6.5 Hz, 3 H), 1.14 (d, J = 6.8 Hz,
3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 178.4, 178.1, 79.7,
77.2, 58.7, 55.5, 47.4, 41.7, 18.5, 15.8, 14.0, 12.6 ppm.
1
132.2, 126.1, 111.0, 80.7, 62.7, 56.6, 43.5, 18.4, 14.7 ppm. The H
and 13C NMR data closely matched those previously reported.[10]
Supporting Information (see footnote on the first page of this arti-
1
cle): H and 13C NMR spectra for all new compounds.
Acknowledgments
General Procedure B: Maillard Condensation: To a solution of
amino lactone (4 equiv.) in THF/H2O (1:1, 0.03 m with respect to
the enone) was added AcOH until the pH was brought to pH 5.
Enone (1 equiv.) was added and the reaction mixture was stirred at
60 °C for 16 h. The reaction was quenched by the addition of H2O,
and the aqueous layer was extracted with EtOAc. The combined
organic extracts were dried with Na2SO4 and concentrated in vacuo
to afford the crude product, which was purified by preparative thin-
layer chromatography (hexanes/EtOAc, 4:1).
The authors gratefully acknowledge the New Zealand Ministry of
Business, Innovation and Employment (MBIE) for financial sup-
port through an International Investment Opportunities Fund
(IIOF) grant.
[1] H. J. Yu, C. C. Chen, B. J. Shieh, J. Nat. Prod. 1998, 61, 1017–
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TBS-Protected Funebral 24a and TBS-Protected Funebrine 25a:
Following general procedure B, reaction of amino lactone 11a
(20 mg, 155 μmol) provided the title compounds 24a (9 mg,
26 μmol, 67%) and 25a (3 mg, 7 μmol, 17%) as pale-yellow oils.
[4] J. L. Guo, Z. M. Feng, Y. J. Yang, Z. W. Zhang, P. C. Zhang,
Biol. Pharm. Bull. 2010, 58, 983–985.
[5] X. G. Tong, L. L. Zhou, Y. H. Wang, C. F. Xia, Y. Wang, M.
Liang, F. F. Hou, Y. X. Cheng, Org. Lett. 2010, 12, 1844–1847.
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[8] S. X. Yu, P. W. Le Quesne, Tetrahedron Lett. 1995, 36, 6205–
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Compound 24a: [α]2D0 = +17 (c = 0.7, CHCl ). IR (neat): ν
=
max
˜
3
2925, 2854, 1781, 1662, 1450, 1191, 1072, 1056, 835, 776 cm–1. H
NMR (400 MHz, CDCl3): δ = 9.41 (s, 1 H), 7.0 (d, J = 4.0 Hz, 1
H), 6.22 (d, J = 4.0 Hz, 1 H), 4.99 (d, J = 11.4 Hz, 1 H), 4.70 (s, 2
H), 4.26–4.19 (m, 1 H), 2.79–2.72 (m, 1 H), 1.61 (d, J = 6.2 Hz, 3
1
1436
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