Journal of Natural Products
Article
4.04 (m, 2H), 2.45 (s, 3H), 2.00−1.86 (m, 2H), 1.72−1.64 (m, 1H),
1.67 (s, 3H), 1.57 (s, 3H), 1.55−1.48 (m, 1H), 1.47−1.38 (m, 1H),
1.14−1.06 (m, 1H), 0.81 (d, J = 6.8 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 144.6, 133.2, 131.5, 129.8, 127.9, 124.3, 69.1, 36.7, 35.7,
28.9, 25.7, 25.3, 21.6, 19.0, 17.6; HRESIMS m/z 311.1670 [M + H]+
(calcd for C17H27O3S, 311.1681).
resulting slurry followed by pouring in 15 mL of H2O. The aqueous
layer was extracted with CH2Cl2 (3 × 20 mL). The combined organic
layers were washed with brine and dried over anhydrous Na2SO4.
Filtration and concentration gave the crude aldehyde, which was
directly subjected to the next step without further purification. To a
suspension of anhydrous CrCl2 (1.94 g, 15.92 mmol) in 20 mL of dry
THF under a nitrogen atmosphere was added a mixed solution of the
above aldehyde and CHI3(2.35 g, 5.97 mmol) in 20 mL of dry THF
via a dropping funnel. A precooled saturated NaCl solution (15 mL)
was poured into the reddish-brown suspension after TLC indicated
the starting material had disappeared. The aqueous layer was
extracted with EtOAc (3 × 20 mL), dried over anhydrous Na2SO4,
and evaporated in vacuo. The residue was subjected to column
(S)-2,6-Dimethyldodec-2-ene (19). Under a nitrogen atmos-
phere, magnesium ribbon (0.60 g) was polished to a silvery-white and
cut into pieces. Then, the magnesium pieces (0.50 g, 20.83 mmol)
were placed in a three-necked flask, to which was added 10 mL of dry
THF followed by the addition of two iodine crystals and a solution of
n-butyl bromide (3.40 g, 24.81 mmol) in THF (10 mL). The mixture
was stirred for 1 h at rt. To a solution of compound 18 (1.00 g, 3.22
mmol) in 5 mL of THF were added CuCl (31.5 mg, 0.32 mmol) and
the above Grignard reagent in sequence. The resulting solution was
stirred at rt until compound 18 disappeared. Saturated NH4Cl
solution (20 mL) was poured into the reaction mixture, which was
then extracted with EtOAc (3 × 20 mL), and the combined organic
layers were concentrated in vacuo. The residue was purified by
column chromatography (pure petroleum ether) on silica gel to get
compound 19 (0.52 g, 82%) as a colorless oil: [α]25D −1.33 (c 0.375,
chromatography (petroleum ether/EtOAc = 20:1) to give compound
1
3 (0.77 g, 70%) as a yellow oil: [α]25 −37.2 (c 0.423, CHCl3); H
D
NMR (400 MHz, CDCl3) δ 7.35−7.33 (m, 5H), 6.46 (dd, J = 14.4,
6.8 Hz, 1H), 6.37 (d, J = 14.4 Hz, 1H), 5.76 (dt, J = 15.6, 14.0 Hz,
1H), 5.34 (dd, J = 15.2, 8.0 Hz, 1H), 5.11 (s, 2H), 4.58 (t, J = 8.0 Hz,
1H), 4.51 (t, J = 6.4 Hz, 1H), 2.35 (t, J = 7.6 Hz, 2H), 2.06 (q, J = 7.2
Hz, 2H), 1.68−1.60 (m, 2H), 1.51 (s, 3H), 1.37 (s, 3H), 1.37 (m,
2H), 1.26 (m, 12H); 13C NMR (100 MHz, CDCl3) δ 173.8, 142.8,
136.9, 136.2, 128.6, 128.2, 124.9, 109.0, 80.9, 79.4, 79.1, 66.1, 34.4,
32.3, 29.6, 29.5, 29.3, 29.2 (2C), 29.0, 28.0, 25.5, 25.0; HRESIMS m/
z 563.1635 [M + Na]+ (calcd for C26H37IO4Na, 563.1629).
CHCl3) {lit. [α]20 −1.0 (c 5.42, CHCl3)};26c 1H NMR (400 MHz,
D
CDCl3) δ 5.11 (tt, J = 7.2, 1.2 Hz, 1H), 2.03−1.90 (m, 2H), 1.68 (d, J
= 0.8 Hz, 3H), 1.61 (s, 3H), 1.39−1.26 (m, 11H), 1.17−1.09 (m,
2H), 0.89 (t, J = 7.2 Hz, 3H), 0.86 (d, J = 6.8 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ 130.9, 125.1, 37.2, 37.0, 32.4, 32.0, 29.7, 27.0,
25.7, 25.6, 22.7, 19.6, 17.6, 14.1; HRESIMS m/z 219.2147 [M + Na]+
(calcd for C14H28Na, 219.2089).
Suzuki Coupling Product 21. Compound 3 (0.24 g, 0.433
mmol) and compound 4 (0.15 g, 0.51 mmol) were dissolved in a
mixed solvent of THF and H2O (10 mL, v/v = 3:1) under a nitrogen
atmosphere, sonicated, and degassed for 20 min. To the solution was
added Pd(PPh3)4 (46.2 mg, 0.04 mmol) at rt. The resultant solution
was allowed to stir for 5 min. Then, EtOTl (48 μL, 0.68 mmol) was
added via a syringe. The reaction mixture was stirred for another 1 h
before adding saturated NaHCO3 solution to basify the solution to
pH 7.0. After filtration and extraction with EtOAc (3 × 20 mL), the
organic layers were concentrated in vacuo. The residue was purified
by column chromatography (petroleum ether/EtOAc = 20:1) to give
compound 21 (0.17 g, 65%) as a colorless oil: [α]25D −13.3 (c 0.075,
Pinacol Vinyl Boronate 4. Method A: To a mixture of
compound 17 (0.95 g, 5.65 mmol) and pinacol vinylboronate (3.00
g, 19.50 mmol) in 15 mL of CH2Cl2 was added Hoveyda−Grubbs II
catalyst (0.35 g, 0.56 mmol). The solution was stirred at reflux
temperature until the completion of the reaction. The solvent was
evaporated in vacuo to give the crude product, which was purified by
silica gel column chromatography (petroleum ether/EtOAc = 50:1)
to provide compound 4 (1.26 g, 76%) as a yellow oil: [α]25D −0.12 (c
4.10, CHCl3); 1H NMR (400 MHz, CDCl3) δ 6.61 (dt, J = 18.0, 6.4
Hz, 1H), 5.40 (d, J = 18.0 Hz, 1H), 2.20−2.06 (m, 2H), 1.44−1.36
(m, 3H), 1.25 (m, 20H), 1.09−1.07 (m, 2H), 0.86 (t, J = 6.4 Hz, 3H),
0.83 (d, J = 6.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 155.3, 83.1,
37.0, 35.5, 33.5, 32.4, 32.0, 29.8, 29.7, 27.0, 24.9 (2C), 22.8, 19.6,
14.2; HRESIMS m/z 317.2624 [M + Na]+ (calcd for C18H35BO2Na,
317.2622). Method B: Except for replacing compound 17 by
compound 19 and adopting 1,2-dicholoro ethane as solvent, a similar
procedure to method A was applied to synthesize compound 4 (1.20
g, 72%).
1
CHCl3); H NMR (400 MHz, CDCl3) δ 7.35−7.34 (m, 5H), 6.19
(dd, J = 14.8, 10.4 Hz, 1H), 6.03 (dd, J = 15.2, 10.8 Hz, 1H), 5.74−
5.66 (m, 2H), 5.46 (dd, J = 15.2, 7.6 Hz, 1H), 5.38 (dd, J = 15.2, 7.6
Hz, 1H), 5.11 (s, 2H), 4.58−4.52 (m, 2H), 2.35 (t, J = 7.6 Hz, 2H),
2.10−2.00 (m, 4H), 1.64 (t, J = 7.6 Hz, 2H), 1.51 (s, 3H), 1.38 (s,
3H), 1.36 (m, 3H), 1.25 (m, 22H), 1.10−1.09 (m, 2H), 0.88 (t, J =
6.8 Hz, 3H), 0.84 (d, J = 6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3)
δ 173.8, 136.5, 136.2, 136.0, 134.2, 129.2, 128.6, 128.2, 126.4, 126.0,
108.4, 80.1, 79.8, 66.1, 37.0, 36.5, 34.4, 32.4, 32.0, 30.3, 29.7, 29.6,
29.5, 29.3, 29.2 (2C), 29.0, 28.2, 27.0, 25.7, 25.0, 22.8, 19.5, 14.2;
HRESIMS m/z 617.4543 [M + Na]+ (calcd for C39H62O4Na,
617.4546).
Cross-Metathesis Product 20. To a mixture of compound 5
(1.67 g, 5.52 mmol) and compound 6 (1.00 g, 6.32 mmol) in 20 mL
of CH2Cl2 was added Grubbs II catalyst (268.7 mg, 0.32 mmol). The
solution was allowed to stir at reflux temperature until the completion
of the reaction. Concentration of the solvent gave the crude product,
which was purified by silica gel column chromatography (petroleum
Amide 2. To a solution of compound 21 (100.0 mg, 0.168 mmol)
in MeOH (10 mL) was added 10% Pd/C (20.0 mg). The suspension
was allowed to stir for 25 min at rt under a hydrogen atmosphere and
filtered; then the filtrate was evaporated in vacuo to provide a crude
carboxylic acid. To a solution of (R)-piperidine-2-carboxylic acid
methyl ester hydrochloride (36.0 mg, 0.20 mmol) in 5 mL of dry
CH2Cl2 was added NaHCO3 (50.0 mg, 0.60 mmol). The mixture was
stirred for 0.5 h before the sequential addition of the above carboxylic
acid, EDCI (77.0 mg, 0.40 mmol), and HOBt (1.15 g, 0.50 mmol).
The solution was allowed to stir at rt until the completion of the
reaction. H2O (10 mL) was poured into the solution, which was then
extracted with CH2Cl2 (3 × 10 mL). The combined organic layer was
dried over anhydrous Na2SO4 and concentrated in vacuo. The residue
was purified by silica gel column chromatography (petroleum ether/
ether/EtOAc = 2:1) to provide compound 20 (1.57 g, 66%) as a
1
colorless oil: [α]25 −5.9 (c 0.625, CHCl3); H NMR (400 MHz,
D
CDCl3) δ 7.34−7.31 (m, 5H), 5.82 (dt, J = 15.2, 14.8 Hz, 1H), 5.47
(dd, J = 15.2, 8.0 Hz, 1H), 5.11 (s, 2H), 4.62 (t, J = 7.6 Hz, 1H), 4.21
(q, J = 5.6 Hz, 1H), 3.58 (t, J = 5.6 Hz, 2H), 2.35 (t, J = 8.0 Hz, 2H),
2.05 (q, J = 7.2 Hz, 2H), 1.86 (t, J = 6.4 Hz, 1H), 1.65−1.62 (m,2H),
1.50 (s, 3H), 1.38 (s, 3H), 1.37 (m, 2H), 1.28−1.25 (m, 12H); 13C
NMR (100 MHz, CDCl3) δ 173.8, 137.1, 136.2, 128.6, 128.2, 124.2,
108.6, 78.4, 78.3, 66.2, 62.3, 34.4, 32.4, 29.5 (2C), 29.3, 29.2 (2C),
29.0, 27.9, 25.3, 25.0; HRESIMS m/z 441.2611 [M + Na]+ (calcd for
C25H38O5Na, 441.2611).
EtOAc = 2:1) to provide compound 2 (92.0 mg, 86%) as a colorless
1
Vinyl Iodide 3. To a solution of oxalyl chloride (0.34 mL, 3.74
mmol) in 8 mL of dry CH2Cl2 was added dropwise a solution of
DMSO (0.63 mL, 8.15 mmol) in 5 mL of CH2Cl2 over 5 min at −60
to − 50 °C under a nitrogen atmosphere. After that, compound 20
(0.86 g, 1.99 mmol) in 10 mL of CH2Cl2 was added to the above
solution. The mixture was allowed to stir for 1 h at the same
temperature. Then, Et3N (1.12 mL, 7.99 mmol) was added to the
oil: [α]25 −36.3 (c 0.08, CHCl3); H NMR (400 MHz, CDCl3) δ
D
5.39 (d, J = 5.2 Hz, 1H), 4.59−4.56 (conformer), 4.02−4.00 (m, 2H),
3.78 (m, 1H), 3.76 (conformer), 3.72 (s, 3H), 3.22 (dt, J = 13.2, 2.8
Hz, 1H), 2.36 (t, J = 7.6 Hz, 2H), 2.24 (m, 1H), 1.73−1.54 (m, 9H),
1.48−1.43 (m, 5H), 1.41 (s, 3H), 1.33 (s, 3H), 1.25 (m, 32H), 1.08−
1.06 (m, 2H), 0.88 (t, J = 6.8 Hz, 3H), 0.83 (d, J = 6.4 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ 173.4, 172.1, 107.3, 78.2, 52.2, 51.8, 43.5,
G
J. Nat. Prod. XXXX, XXX, XXX−XXX