A. C. Benniston, S. Yang, H. Lemmetyinen, N. V. Tkachenko
FULL PAPER
1 H, JЈ=3 Hz, H4), 3.55–3.50 (m, 2 H, CH2CH3), 3.44–3.39 (m, 2 pound (1.26 g, 2.0 mmol) in ethanol (80 mL) and water (8 mL) and
H, CH2CH3), 2.93 (s, 6 H, NCH3), 1.34–1.29 (t, J = 7 Hz, 3 H, the mixture was refluxed for 4 days. To the cooled mixture was
CH2CH3), 1.25–1.20 (t, J = 7 Hz, 3 H, CH2CH3) ppm. 13C NMR added water (100 mL) and DCM (100 mL). The aqueous layer was
(100 MHz, CDCl3): δ = 153.2 (OCON), 152.3, 151.6, 138.5, 111.7,
107.5 (5ϫ Ar-C), 73.4 (C-I), 42.2 (CH2CH3), 41.9 (CH2CH3), 40.3
(NCH3), 14.3 (CH3),13.3 (CH3) ppm.
neutralized with 1n HCl and extracted with DCM. The combined
organic layers were washed with water, separated, dried (MgSO4)
and evaporated under reduced pressure to give the crude product
which was purified by column chromatography [silica gel, DCM/
acetone (1:1)] to afford BD (0.572 g, 1.0 mmol, 54% yield). 1H
NMR (400 MHz, CDCl3): δ = 7.61 (s, 1 H), 7.43–7.42 (d, J = 8 Hz,
1 H), 7.32–7.30 (d, J = 8 Hz, 1 H), 6.88–6.86 (d, J = 8 Hz, 1 H),
6.58 (s, 1 H), 6.50–6.48 (d, J = 8 Hz, 1 H) (6ϫ Ar-H), 3.00 (s, 6
H, 2ϫ NCH3), 2.63 (s, 2 H, 2ϫ OH), 2.37 (s, 6 H, 2ϫ CH3), 2.29–
2.22 (q, J = 7 Hz, 4 H, 2ϫ CH2CH3), 1.47 (s, 6 H, 2ϫ CH3), 0.93–
0.89 (t, J = 7 Hz, 6 H, 2ϫ CH2CH3) ppm. 13C NMR (100 MHz,
CDCl3): δ = 155.0, 154.1, 153.3, 152.2, 141.0, 137.7, 135.2, 132.5,
132.0, 127.2, 120.5, 117.5, 114.9, 106.4, 102.0, 40.8, 17.3, 14.9, 12.3,
12.1 ppm (Note: two carbon resonances are missing because of ac-
cidental equivalence). 11B NMR (128 MHz, CDCl3): δ = 1.69
(br) ppm. ES-MS m/z fnd 515.4 calcd. [M – OH]+ 515.4.
Preparation of 6: To a single-necked flask (50 mL) containing 5
(1.3 g, 3.6 mmol) was added pinacolborane (1.1 mL, 7.6 mmol), tri-
ethylamine (6.0 mL) and THF (40 mL). The solution was bubbled
with dry N2, followed by the addition of PdCl2(PPh3)2 (0.2 g,
0.28 mmol). The reaction mixture was heated and refluxed over-
night, then cooled to room temp. and diluted with ethyl acetate
(100 mL). The organic layer was washed three times with brine,
separated and dried with CaCl2. After filtration the solvent was
removed and the residue was purified by column chromatography
(silica gel, DCM/acetone, 50:1) to give the product (0.843 g,
2.3 mmol, 65% yield). 1H NMR (400 MHz, CDCl3): δ = 7.61–7.58
(d, J = 9 Hz, 1 H, H3), 6.50–6.47 (dd, J = 9 Hz, 1 H, JЈ=2 Hz, H4),
6.35–6.34 (d, J = 2 Hz, 1 H, H6), 3.51–3.46 (q, J = 5 Hz, 2 H,
CH2CH3), 3.39–3.33 (q, J = 5 Hz, 2 H, CH2CH3), 2.94 (s, 6 H, 2ϫ
NCH3), 1.27 (s and m, 12 H + 3 H, 12ϫ CH3 + CH2CH3), 1.19–
1.16 (t, J = 5 Hz, 3 H, CH2CH3) ppm. 13C NMR (100 MHz,
CDCl3): δ = 157.9 (OCON), 154.9, 153.7, 137.1, 108.6, 105.7, 82.7
(6ϫ Ar-C), 41.7 (CH2CH3), 41.5 (CH2CH3), 39.9 (NCH3), 24.8
(OCC3), 13.9 (CH2CH3), 13.4 (CH3) ppm (Note: one carbon reso-
nance is missing because of accidental equivalence). 11B NMR
(128 MHz, CDCl3): δ = 29.4 (s) ppm.
Supporting Information (see footnote on the first page of this arti-
1
cle): Copies of H NMR and 13C NMR spectra for BD and PBD,
binding model and data, additional figures molecular modeling
pictures and CV data.
Acknowledgments
The authors thank the Engineering and Physical Sciences Research
Council (EPSRC) (EP/G04094X/1) for financial support. Mass
spectrometry data were acquired at the EPSRC UK National Mass
Spectrometry Facility at Swansea.
Preparation of PBD: To compounds 6 (532 mg, 1.4 mmol) and 3
(913 mg, 1.4 mmol) in DME (50 mL) in a 250 mL two-necked flask
was added an aqueous solution of Na2CO3 (467 mg in 20 mL of
water). The solution was subjected to four freeze-pump-thaw cycles
to remove dioxygen. [Pd(PPh3)4] (170 mg, 0.15 mmol) was then
added under nitrogen. After degassing again, the mixture was re-
fluxed overnight and then cooled to room temperature. Water
(50 mL) and ethyl acetate (100 mL) were poured into the mixture
and the isolated organic layer was dried (MgSO4), filtered and
evaporated under reduced pressure to give the crude product, which
was purified by column chromatography [silica gel DCM/acetone
(100:1)] to afford the pure product. (196 mg, 0.27 mmol, 19%
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yield). H NMR (400 MHz, CDCl3): δ = 7.44–7.42 (d, J = 9 Hz, 1
7024–7039.
H), 7.15–7.09 (m, 3 H), 6.60–6.58 (dd, J = 9 Hz, 1 H, JЈ=2 Hz), [5] L. F. Agnati, M. Zoli, I. Strömberg, K. Fuxe, Neuroscience
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6.52–6.51 (d, J = 2 Hz, 1 H) (6ϫ Ar-H), 3.025–3.18 (m, 8 H, 4ϫ
NCH2CH3), 2.95 (s, 6 H, 2ϫ NCH3), 2.25 (s, 6 H, 2ϫ CH3), 2.33–
2.28 (q, J = 5 Hz, 4 H, 2ϫ CH2CH3), 1.47 (s, 6 H, 2ϫ CH3), 1.14–
1.08 (q, J = 5 Hz, 6 H, 2ϫ CH2CH3), 1.00–0.96 (m, 12 H, 4ϫ
NCH2CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 153.9, 153.7,
153.6, 151.3, 150.1, 149.5, 139.1, 138.6, 135.1, 132.6, 132.4, 132.2,
131.6, 130.7, 41.9, 41.7, 41.6, 41.4, 40.5, 17.0, 14.6, 14.2, 13.7, 13.3,
13.0, 12.4, 11.8 ppm. 11B NMR (128 MHz, CDCl3): δ = –0.153 (t,
J = 32 Hz) ppm. 19F NMR (376 MHz, CDCl3): δ = –145.67 (q, J
= 32 Hz) ppm.
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Preparation of BD: NaOH (3.25 g, 81.3 mmol, 40 equiv.) was added
to a solution of PBD (1.48 g, 2.0 mmol) in methanol (60 mL) and
the mixture was refluxed overnight. After cooling to room temp.
water (100 mL) and DCM (100 mL) were poured into the mixture.
The separated aqueous layer was neutralized with 1 n HCl and
extracted with DCM. The combined organic fractions were washed
with water, dried (MgSO4), filtered and evaporated under reduced
pressure to give the crude product which was purified by column
chromatography on silica gel with DCM/acetone (1:1) to afford
the mono-protected compound (1.26 g, 2.0 mmol). KOH (7.00 g,
125 mmol) was added to a solution of the mono-protected com-
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