Stereoselective synthesis of sarmentine

Full text of DOI:10.1134/S1070363211090337

ISSN 1070-3632, Russian Journal of General Chemistry, 2011, Vol. 81, No. 9, pp. 1915–1917. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © R.N. Shakhmaev, A.U. Ishbaeva, A.Sh. Sunagatullina, V.V. Zorin, 2011, published in Zhurnal Obshchei Khimii, 2011, Vol. 81,
No. 9, pp. 1578–1580.
LETTERS
TO THE EDITOR
Stereoselective Synthesis of Sarmentine
R. N. Shakhmaev, A. U. Ishbaeva, A. Sh. Sunagatullina, and V. V. Zorin
Ufa State Petroleum Technical University, ul. Kosmonavtov 1, Ufa, 450062 Russia
e-mail: biochem@rusoil.net
Received February 21, 2011
DOI: 10.1134/S1070363211090337
Natural (2E,4E)-dienamides of Piperaceae and
Echinacea species have a broad spectrum of
therapeutic action, and in the past decade they attracted
a wide attention [1–7]. Sarmentine, the 1-[(2E,4E)-
deca-2,4-dienoyl]pyrrolidine, was first isolated from
the Piper sarmentosum fruits [8]. It possesses sedative,
analgesic, and antibacterial activities [9]. Recently it
was found to manifest antitubercular and antiplazmo-
dial activities [10].
with an insignificant content of isomeric products
(1%). The total yield of the desired product is 83%
relative to the starting 1-heptyne.
(i-Bu) AlH, I2
I
2
C H
C
5
H
11
5
11
IV
II
O
HN
O
N
The main task in a sarmentine synthesis is the
stereoselective construction of conjugated (2E,4E)-
diene system bonded with the amide function.
Previously for this purpose were used the elimination
Cl
CH Cl
2 2
V
III
C H
5
O
11
Pd(OAc)2
Bu NCl, K CO
3
[11] and homologenization of (2E,4E)-pentadienyl-1-
N
II + III
carbonyl precursors [12, 13], isomerization of alkynyl-
amides [14] and stereoselective iodosulfonylation of
4
2
I
(
2E,4E)-pentadienamide followed by the cross-
The structure and stereochemical purity of sarmen-
tine I was confirmed by the H and C NMR spec-
1
13
coupling with n-pentylmagnesium bromide [15]. These
methods are characterized by the low overall yield of
the target product and the low stereoselectivity.
trometry, GLC analysis, and gas chromatography–
1
mass spectrometry. In the H NMR spectrum of the
product I the coupling constants of vinyl hydrogen
atom at C atom is 7.14 Hz, which indicates clearly the
double bond of transoid configuration.
We investigated the possibility of stereoselective
synthesis of 1-[(2E,4E)-deca-2,4-dienoyl]pyrrolidine I
on the basis of direct cross-coupling of (1E)-1-
iodohept-1-ene II with 1-acryloylpyrrolidine III (the
Mizoroki–Heck reaction) [16–19]. The initial (1E)-1-
iodohept-1-ene II was obtained via the hydroalumina-
tion-iodination of 1-heptyne IV in an yield of 88% by
the optimized procedure [20]. The other building-block
in the cross-coupling reaction, 1-acryloylpyrrolidine
III, was synthesized through the acrylic acid
chlorodehydroxylation followed by the amidation of
acryloyl chloride V with pyrrolidine.
2
The IR spectra were recorded from a thin layer on a
1
Prestige-21 Shimadzu IR-Fourier spectrometer. The H
13
and C NMR spectra were recorded on a Bruker AM-
3
00 instrument operating at 300 and 75.47 MHz,
respectively) from solutions in CDCl . The chromato-
3
graphic and mass spectral analysis was performed on a
Chromatec-Crystal 5000 complex equipped with a
Finnigan DSQ mass-selective detector (electron impact
at 70 eV). A Restek Rtx-5ms capillary column (5%
diphenylpolysiloxane, 95% dimethylpolysiloxane, length
30 m) was used, the evaporator temperature 250°C, the
ionization cell temperature 250°C. The analysis was
carried out with programming temperature from 50 to
The reaction of (1E)-1-iodohept-1-ene with 1-
acrciloylpyrrolidine in the presence of Pd(OAc) , a
2
base, and tetrabutylammonium chloride in DMF yields
quantitatively 1-[(2E,4E)-deca-2,4-dienoyl]pyrrolidine
1
915

1
916
SHAKHMAEV et al.
–
1
2
50°C at a heating rate 10 deg min , carrier gas
1-[(2E,4E)-Deca-2,4-dienoyl]pyrrolidine (I). To a
mixture of 0.46 g of K СО , 0.37 g of Bu NCl, 0.3 g of
1E)-1-iodohept-1-ene II, and 0.25 g of 1-acryloyl-
–
1
helium (1.1 ml min ).
2
3
4
(
(
1E)-1-Iodohept-1-ene (II) was obtained by the
modified procedure [20]. To a solution of 0.96 g of 1-
heptyne IV in 10 ml of anhydrous hexane 15 ml of
M diisobutyl aluminum hydride solution in hexane was
added. The mixture was stirred for 6 h at 55°C in an
argon atmosphere and cooled to –50°C. Then to this
mixture a solution of 2.79 g of iodine in 10 ml of
anhydrous THF was added over 30 minutes. The
reaction mixture was warmed within 1 h to room
temperature and stirred at this temperature for another
pyrrolidine III in 0.9 ml of DMF was added a solution
of 0.006 g of Pd(OAc) in 0.1 ml of DMF. The reac-
2
tion mixture was purged with argon and heated for 5 h
at 70°С under stirring. After consumption of (1E)-1-
iodohept-1-ene II (TLC control), 3 ml of water and
1
3
ml of hexane was added to the mixture. The organic
layer was separated, and the aqueous layer was
extracted with hexane (2×3 ml). The combined organic
solutions were washed with water (5 ml), dried over
Na SO , and concentrated. The crude product was
2
4
1
2 h. To the mixture 25 ml of 10% sulfuric acid
purified by the column chromatography (SiO2,
solution was added under ice-cooling. The organic
layer was separated, and the aqueous layer was
extracted with hexane (3×15 ml). The combined
organic solutions were washed with brine, dried over
Na SO , and concentrated. The product was isolated
by the column chromatography (SiO , hexane–chloro-
form, 6:1). Yield 1.98 g (88%). IR spectrum, ν, cm :
955, 2924, 2855, 1605, 1458, 1209, 1173, 939. H
hexane–ethyl acetate, 9:1→4:6). Yield 0.28 g (94%).
–
1
IR spectrum, ν, cm : 2955, 2926, 2870, 1653, 1624,
1
1
600, 1425, 999. H NMR spectrum, δ, ppm: 0.89 t
(
(
3H, CH ), 1.26–1.47 m (6H, 3 CH ), 1.81–2.03 m
3
2
2
4
4H, 2 CH CH N), 2.15 q (2H, CH CH=, J 7.0 Hz),
2
2
2
2
–
1
3.46–3.58 m (4H, 2 CH
2
N), 6.02–6.23 m (2H, 2 CH=),
2
1
6.10 d (1H, C H=, J 14.7 Hz), 7.22–7.35 m (1H, CH=).
2
1
3
10
9
С NMR spectrum, δ , ppm: 13.76 (С ), 22.24 (C ),
С
NMR spectrum, δ, ppm: 0.87 t (3H, CH ), 1.21–1.43 m
3
7
2
4.10 (CH CH N), 25.86 (CH CH N), 28.23 (C ),
2
2
2
2
(
(
6H, 3CH ), 2.03 q (2H, CH CH=, J 6.9 Hz), 5.96 d
2 2
1H, C H=, J 14.4 Hz), 6.45–6.54 m (1H, C H=). С
NMR spectrum, δ , ppm: 13.91 (С ), 22.33 (C ), 27.96
C ), 31.02 (C ), 35.93 (C ), 74.24 (C ), 146.65 (C ).
Mass spectrum, m/z (I , %): 224 (34) [M] , 167 (24),
54 (55), 97 (22), 69 (13), 55 (100), 41 (23), 39 (13).
8
6
1
2
13
31.11 (C ), 32.69 (C ), 45.57 (CH
119.66 (C ), 128.50 (C ), 141.86 (С or С ), 142.79 (C
or C ), 164.89 (C ). Mass spectrum, m/z (Irel, %): 221
(22) [M] , 151 (29), 150 (100), 98 (27), 95 (26), 81
2
N), 46.17 (CH N),
2
2
4
5
3
3
7
6
С
5
1
4
5
3
1
2
(
+
+
rel
(
(
76), 70 (46), 69 (30), 67 (27), 55 (36), 53 (23), 41
28).
1
1-Acryloylpyrrolidine (III). To a solution of 1.81 g
of acryloyl chloride V in 20 ml of anhydrous di-
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–
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 81 No. 9 2011

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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 81 No. 9 2011