Molecules 2019, 24, 3764
7 of 9
lansiumamide B (
2
) as yellowish oil, which would solidify after storage in the refrigerator (1.03 g, 95%
yield). In order to obtain the analytical sample, recrystalization was carried out with diethyl ether and
◦
◦
1
yellowish plates were secured. Mp = 73–74 C. (lit. 72–73 C) [
J = 15.6 Hz, 1H), 7.47–7.44 (m, 2H), 7.34–7.28 (m, 7H), 7.25–7.20 (m, 1H), 6.93 (d, J = 15.6 Hz, 1H), 6.50
d, J = 8.4 Hz, 1H), 6.24 (d, J = 8.4 Hz, 1H), 3.09 (s, 3H). 13C NMR (100 MHz, CDCl3)
: 166.6, 142.8,
35.3, 134.5, 129.8, 128.9, 128.8 (2 C), 128.7 (4 C), 128.2, 128.1 (2 C), 125.2, 118.4, 34.8. Anal. calcd for
C H NO: C, 82.10; H, 6.51; N, 5.32. Found: C, 82.18; H, 6.58; N, 5.23.
7] H NMR (400 MHz, CDCl ) δ: 7.63 (d,
3
(
1
δ
×
×
×
18
17
3
.3. Total Synthesis of Alatamide
3
.3.1. Synthesis of (E)-1-(2-iodovinyl)-4-methoxybenzene (9)
4-Methoxy-cinnamic acid (8) (1.43 g, 8 mmol) was dissolved in dichloromethane (12 mL).
Subsequently, Et N (0.23 mL, 1.6 mmol) was added followed by the addition of N-iodosuccinamide
3
(
NIS) (2.16 g, 9.6 mmol), and the reaction was allowed to run for 30 min. After the completion of reaction,
the reaction mixture was evaporated under reduced pressure at a low temperature. The residue
was purified by flash column chromatography on silica gel using eluents (petroleum ether/ethyl
acetate = 20/1) to afford (E)-1-(2-iodovinyl)-4-methoxybenzene (
9
) as brown solid (1.40 g, 67% yield).
◦
◦
1
Mp = 99–100 C. (lit. 98–99 C) [25] H NMR (400 MHz, CDCl )
δ: 7.36 (d, J = 14.8 Hz, 1H), 7.23 (dd,
3
13
J = 6.8, 2.0 Hz, 1H), 6.85 (dd, J = 6.8, 2.0 Hz, 1H), 6.63 (d, J = 14.8 Hz, 1H), 3.81 (s, 3H). C NMR
(
100 MHz, CDCl ) δ: 159.8, 144.4, 130.7, 127.4 (2×C), 114.1 (2×C), 73.8, 55.4.
3
3
.3.2. Synthesis of Alatamide (7)
A
Schlenk tube was charged with CuI (48 mg, 0.25 mmol, and
5
mol%),
Cs CO3 (2.44 g, 7.5 mmol) and benzamide (0.726 g, 6.0 mmol), and evacuated and
2
0
backfilled with argon. N,N -Dimethylethylenediamine (54
µL, 0.50 mmol, and 10 mol%),
(E)-1-(2-iodovinyl)-4-methoxybenzene (
9
) (1.30 g, 5.0 mmol) and THF (10.0 mL) were added under
argon. The Schlenk tube was sealed, immersed in a preheated oil bath; the reaction mixture was
◦
stirred at 60 C until the complete consumption of starting material was observed by TLC (5 h).
The reaction vessel was removed from the oil bath and the resulting suspension was allowed to reach
room temperature, then, it was filtered through a plug silica gel eluting with ethyl acetate (50 mL).
The filtrate was concentrated and the residue was purified by flash chromatography on silica gel using
eluents (petroleum ether/ethyl acetate = 5/1) to provide alatamide (
7
) as white solid (1.06 g, 84% yield).
: 7.95 (br, 1H), 7.85–7.82 (m, 2H),
.61 (dd, J = 14.8, 10.8 Hz, 1H), 7.56–7.52 (m, 1H), 7.49–7.44 (m, 2H), 7.30–7.26 (m, 2H), 6.86–6.82 (m,
H), 6.22 (d, J = 14.8 Hz, 1H), 3.80 (s, 3H). 13C NMR (100 MHz, CDCl3)
: 164.3, 158.6, 133.5, 132.0,
C), 128.5, 127.0 (2 C), 126.7 (2 C), 121.3, 114.1 (2 C), 113.3, 55.2. Anal. calcd for C H NO :
C, 75.87; H, 5.97; N, 5.53. Found: C, 75.80; H, 6.13; N, 5.38.
◦
◦
1
Mp = 176–178 C. (lit. 178–180 C) [19] H NMR (400 MHz, CDCl )
δ
3
7
2
δ
128.7 (2
×
×
×
×
16
15
2
4
. Conclusions
We have accomplished the total synthesis of lansiumamides A, B and alatamide in three steps with
a 48% yield from phenylacetylene, four steps with a 46% yield from phenylacetylene and two steps with
a 56% yield from 4-methoxycinnamic acid, respectively, by taking advantage of the copper-catalyzed
Buchwald coupling. The syntheses are concise, convergent, practical and can be carried out on a
one-gram scale. This approach could give either Z or E-configured enamide moiety in natural products
with absolute stereocontrol. Further exploration of the strategy for the generation of novel analogues
for biological evaluation is ongoing in our laboratory.
Supplementary Materials: The following are available online. Copies of H, 13C, spectra of new compounds.
1
Author Contributions: L.S. and H.X. conceived and directed the project. R.L., X.L., Q.S., B.G., Y.H., Y.S. and
M.-A.O. performed the experiments. L.S. wrote the paper.