Journal of Natural Products
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was then added, causing the solution to turn dark orange. The reaction
was monitored by LCMS, and after 1 h, the solution was poured into
ether (10 mL), washed with brine (5 mL), and dried over Na2SO4.
The organic phase was concentrated in vacuo, and the residue was
purified by flash column chromatography (gradient: 5% to 20% EtOAc
in hexanes with 2% NEt3, silica gel) to afford the title compound as a
dark orange solid (10.6 mg, 80%). IR (neat) 3112, 2922, 2853, 1624,
Hz, 1H), 2.52−2.38 (dtd, J = 13.8, 4.3, 1.3 Hz, 1H), 2.38−2.25 (dddd,
J = 14.1, 12.9, 7.1, 4.3 Hz, 1H), 2.11−1.82 (m, 5H), 1.82−1.56 (m,
3H), 1.46−1.18 (m, 7H), 0.95−0.83 (t, J = 6.8 Hz, 3H); 13C NMR
(125 MHz, CDCl3) δ 211.52, 132.38, 126.38, 77.29, 77.23, 77.03,
76.78, 49.43, 41.77, 34.94, 31.49, 29.22, 27.75, 27.57, 24.44, 22.56,
14.07; HRMS (ESI) exact mass calcd for C13H23O [M + H+]
195.1743, found 195.1752.
1
1555, 1467, 1378, 1346, 1287, 1233; H NMR (500 MHz, CD2Cl2)
trans-1-((E)-3-(Benzyloxy)prop-1-enyl)-2-((Z)-hept-1-enyl)-
cyclohexanol (27). To a solution of (E)-1-benzyloxy-3-iodo-2-
propene27 (96 mg, 0.35 mmol) in Et2O (4.5 mL) at −78 °C was
added a solution of n-BuLi in hexanes (135 μL, 2.52 M). The mixture
was allowed to stir for 1 min prior to addition of ketone 26 (40 mg,
0.20 mmol) in Et2O (1.5 mL) at −78 °C. The reaction mixture was
allowed to stir for 30 min before being warmed to 0 °C and quenched
with saturated NH4Cl solution (2 mL). The organic layer was
separated, and the aqueous layer extracted with EtOAc (3 × 10 mL).
The combined organic layers were washed with brine (20 mL), dried
(Na2SO4), and concentrated in vacuo. Purification by flash
chromatography (5−10% EtOAc in hexanes) afforded the title
compound (49 mg, 72%): IR (neat) 3476, 3010, 2929, 2855, 1452,
6.73 (s, 1H), 6.61 (s, 1H), 6.59 (s, 1H), 6.25 (s, 1H), 6.09 (t, 1H, J =
2.7 Hz), 6.01 (s, 1H), 3.88 (s, 3H), 2.46 (m, 1H), 2.16 (br s, 2H), 1.56
(m, 1H), 1.48−1.40 (m, 4H), 1.23 (m, 2H), 1.18−1.04 (m, 7H), 0.75
(t, 3H, J = 7.6 Hz), 0.66 (br m, 1H); 13C NMR (125 MHz, CD2Cl2)
169.4, 159.8, 143.2, 138.8, 129.1, 128.3, 128.1, 122.5, 118.9, 116.5,
112.6, 110.5, 95.9, 58.9, 38.1, 37.0, 36.0, 30.6, 28.2, 28.1, 27.6 (2), 23.3,
23.1, 14.2; HRMS (ESI+) exact mass calcd for C25H34N3O [M + H+]
392.2696, found 392.2703.
The HCl salt of 4 was obtained using the same procedure but by
purifying the product by silica gel chromatography under different
conditions (gradient: CHCl3 to 1% MeOH/CHCl3, silica gel) (11 mg
of 4·HCl from 6 mg of 7, 95%). IR (neat) 3156, 2953, 2869, 1632,
1
1
1359, 1114, 1068, 973, 909 cm−1; H NMR (500 MHz, CDCl3) δ
1602, 1572, 1346, 1268, 1115, 962; H NMR (500 MHz, CDCl3)
12.80 (s, 1H), 12.63 (s, 2H), 7.25 (s, 1H), 7.00 (s, 1H), 6.94 (s, 1H),
6.65 (d, 1H, J = 3 Hz), 6.37 (s, 1H), 6.10 (s, 1H), 4.03 (s, 3H), 3.35
(m, 1H), 2.76 (m, 2H), 2.15 (m, 1H), 1.71 (m, 2H), 1.63−1.58 (m,
4H), 1.45−1.38 (m, 4H), 1.30−1.22 (m, 4H), 1.14 (m, 1H), 0.88 (t,
3H, J = 7.8 Hz); 13C NMR (125 MHz, CDCl3) 165.9, 153.0, 147.8,
132.5, 127.1, 126.6, 125.8, 122.4, 120.8, 117.2, 116.2, 111.8, 92.9, 58.6,
37.0, 36.6, 35.9, 30.1, 27.3, 27.1, 26.9, 26.6, 23.6, 22.7, 14.1.
7.37−7.31 (m, 4H), 7.30−7.27 (dt, J = 6.2, 3.0 Hz, 1H), 5.77−5.71 (d,
J = 2.5 Hz, 2H), 5.44−5.37 (dd, J = 11.1, 7.1 Hz, 1H), 5.35−5.26 (m,
1H), 4.51−4.44 (m, 2H), 4.04−3.96 (m, 2H), 2.40−2.25 (ddd, J =
11.4, 9.7, 4.2 Hz, 1H), 2.04−1.89 (m, 2H), 1.78−1.41 (m, 7H), 1.35−
1.20 (m, 7H), 0.94−0.80 (t, J = 6.9 Hz, 3H); 13C NMR (125 MHz,
CDCl3) δ 141.16, 138.40, 130.98, 129.65, 128.41, 128.36, 127.77,
127.75, 127.56, 123.70, 73.07, 71.79, 70.49, 43.55, 38.04, 31.59, 29.42,
28.46, 27.78, 25.22, 22.62, 21.34, 14.12; HRMS (ESI) exact mass calcd
for NaC23H34O2 [M + Na+] 365.2451, found 365.2447.
trans-(E)-3-(Benzyloxymethyl)-4-pentylcyclodec-5-enone (28). To
a stirring suspension of KH (12 mg, 0.3 mmol) in Et2O (4 mL) at 0
°C was added hexamethyldisilazane (63 μL, 0.3 mmol). The
suspension was stirred for 30 min at room temperature prior to
addition into a stirring solution of allylic alcohol 27 (50 mg, 0.15
mmol) and 18-crown-6 ether (79 mg, 0.3 mmol) in Et2O (5 mL) at 0
°C. The resulting yellow solution was stirred for 18 h at room
temperature. The reaction was quenched with saturated NH4Cl
solution (1 mL) and poured into H2O (5 mL). The organic layer was
separated, and the aqueous layer was extracted with Et2O (3 × 10
mL). The combined organic phases were dried (Na2SO4), filtered, and
concentrated in vacuo. Purification by flash chromatography on silica
gel (3−15% EtOAc in hexanes) afforded the title compound (23 mg,
49%): IR (neat) 2928, 2857, 1704, 1496, 1361, 1090, 736 cm−1 (note:
NMR spectra were significantly obscured, presumably due to alkene
anisotropy); 1H NMR (500 MHz, CDCl3) δ 7.29−7.25 (m, 4H),
7.24−7.20 (td, J = 5.2, 4.1, 2.5 Hz, 1H), 5.44−4.96 (m, 2H), 4.55−
4.40 (m, 2H), 3.64−3.22 (m, 2H), 2.44−2.09 (m, 5H), 2.00−1.77 (m,
2H), 1.72−1.55 (m, 1H), 1.45−1.11 (m, 8H), 1.07−0.92 (m, 1H),
0.92−0.68 (t, J = 7.0 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 128.37,
127.67, 33.45, 22.70, 14.16; HRMS (ESI) exact mass calcd for
NaC23H34O2 [M + Na+] 365.2451, found 365.2443.
trans-3-(Hydroxymethyl)-4-pentylcyclodecanone (29). To a sol-
ution of cyclodecanone 28 (23 mg, 0.07 mmol) in dry MeOH (3 mL)
was added 10% Pd/C (7 mg). The flask was purged with H2, and the
solution allowed to stir under a balloon of H2 at room temperature for
19 h and recharged with an additional 5 mg of 10% Pd/C. After an
additional 18 h the solution was filtered through Celite, eluting with 25
mL of ethyl acetate, and concentrated in vacuo. Purification by flash
chromatography (20% EtOAc in hexanes) afforded the title compound
(15 mg, 85%): IR (neat) 3417, 2925, 2857, 1698, 1469, 1045 cm−1; 1H
NMR (500 MHz, CDCl3) δ 3.74−3.66 (dd, J = 10.4, 4.5 Hz, 1H),
3.55−3.46 (t, J = 9.8 Hz, 1H), 2.93−2.82 (m, 1H), 2.61−2.50 (ddd, J
= 14.2, 10.4, 3.5 Hz, 1H), 2.50−2.41 (ddd, J = 15.1, 7.6, 3.8 Hz, 1H),
2.41−2.31 (tt, J = 13.8, 4.3 Hz, 2H), 2.10−1.96 (m, 1H), 1.95−1.85
(d, J = 6.6 Hz, 1H), 1.76−1.57 (m, 2H), 1.57−1.47 (m, 2H), 1.46−
1.14 (m, 14H), 0.92 − 0.82 (t, J = 7.1 Hz, 3H); 13C NMR (125 MHz,
CDCl3) δ 215.86, 77.29, 77.24, 77.04, 76.78, 64.55, 43.44, 41.83,
40.96, 36.33, 32.13, 31.71, 28.51, 27.67, 25.58, 25.52, 24.27, 23.99,
B. Synthesis of Streptorubin B-5C (STRB-5C). trans-2-((Z)-
Hept-1-enyl)cyclohexanol (25). To a solution of heptanedial (0.26 g,
2 mmol) in dichloromethane (20 mL) was added (rac)-proline (23
mg, 0.2 mmol) at room temperature. The heterogeneous mixture was
stirred for 15 h, after which the solution became clear and
homogeneous. To a heterogeneous solution of hexyltriphenylphos-
phonium bromide (1.11 g, 2.6 mmol) in THF (20 mL) at 0 °C was
added sodium hexamethyldisilazane (2.6 mL, 2.6 mmol, 1 M in THF),
upon which the solution turned bright orange. The ylide solution was
allowed to stir for 1 h 20 min prior to addition of aldehyde solution via
cannula at 0 °C, upon which the solution turned cloudy and white.
After 3 h, the reaction mixture was quenched with saturated NH4Cl
(20 mL), and the ether layer separated. The aqueous/halogenated
layers were extracted with Et2O (3 × 20 mL), washed with brine (60
mL), and dried with NaSO4 and concentrated under reduced pressure.
The residue was purified by flash column chromatography (10% Et2O
in hexanes, silica gel) to afford the title compound as a 5:1 mixture of
diastereomers (260 mg, 66%). IR (neat) 3430, 2998, 2927, 2856, 1449,
1
1076 cm−1; H NMR (500 MHz, CDCl3) δ 5.63−5.55 (dt, J = 11.2,
7.4 Hz, 1H), 5.21−5.12 (ddt, J = 11.3, 9.8, 1.6 Hz, 1H), 3.24−3.15 (m,
1H), 2.28−2.17 (dtd, J = 12.9, 9.8, 3.7 Hz, 1H), 2.14−1.98 (m, 4H),
1.86−1.81 (d, J = 1.9 Hz, 1H), 1.81−1.74 (dt, J = 8.1, 2.7 Hz, 1H),
1.69−1.56 (m, 4H), 1.45−1.19 (m, 13H), 1.19−1.07 (tdd, J = 13.3,
11.3, 3.6 Hz, 1H), 0.92−0.85 (t, J = 6.7 Hz, 3H); 13C NMR (125
MHz, CDCl3) δ 133.47, 131.55, 73.83, 44.85, 33.48, 31.51, 31.45,
29.62, 27.79, 25.26, 24.85, 22.58, 14.08; HRMS (TOF EI+) exact mass
calcd for C13H24O [M+] 196.1827, found 196.1812.
(Z)-2-(Hept-1-enyl)cyclohexanone (26). To a solution of freshly
distilled oxalyl chloride (75 μL, 0.86 mmol) in DCM (3 mL) at −78
°C was added dropwise DMSO (70 μL, 0.99 mmol). The solution was
stirred for 5 min, after which a solution of secondary alcohol 25 (140
mg, 0.71 mmol) in DCM (3 mL) was added. The solution was stirred
for 20 min, followed by addition of i-Pr2NEt (0.618 mL, 3.55 mmol)
dropwise. The solution was stirred for 10 min before being warmed to
0 °C in an ice bath. The solution was further stirred at 0 °C for 30 min,
then poured into H2O (15 mL). The organic phase was collected, and
the aqueous layer extracted with DCM (2 × 10 mL). The combined
organic layers were dried (Na2SO4), filtered, and concentrated in
vacuo. Purification by flash chromatography (10% EtOAc in hexanes,
silica gel) afforded the title compound (92 mg, 67%): IR (neat) 2930,
2859, 1712, 1449, 1340, 1310, 1126 cm−1; 1H NMR (500 MHz,
CDCl3) δ 5.61−5.48 (m, 2H), 3.33−3.21 (dddd, J = 10.7, 7.7, 5.6, 1.2
F
dx.doi.org/10.1021/np400531b | J. Nat. Prod. XXXX, XXX, XXX−XXX