The Journal of Organic Chemistry
Article
Rf = 0.4 (10% EtOAc−hexane). Major (17): [α]2D4 = +70.82 (c 0.83,
CHCl3); IR (neat) υmax: 3508, 2930, 2856, 1687, 1465, 1255, 1162,
0.08 (s, 3H), 0.07 (s, 3H), 0.06 (s, 3H), 0.05 (s, 6H) ppm; 13C NMR
(75 MHz, CDCl3): δ 201.0, 171.9, 136.6, 129.4, 128.9, 127.2, 70.0,
68.7, 67.4, 63.3, 46.9, 45.8, 37.8, 36.5, 32.8, 32.1, 29.8, 29.4, 25.9,
25.8, 25.8, 25.0, 18.3, 18.1, 18.0, −4.1, −4.2, −4.2, −4.3, −5.3 ppm;
Mass (ESI-MS) m/z: 804 [M + Na]+; HRMS (ESI): Calcd for
C40H75O4NNaS2Si3 [M + Na]+ 804.43375, found 804.43339.
1
1097, 835, 774 cm−1; H NMR (300 MHz, CDCl3): δ 7.38−7.27 (m,
5H), 5.44−5.33 (m, 1H), 4.60−4.49 (m, 1H), 4.05−3.94 (m, 1H),
3.71 (s, 1H), 3.60 (t, J = 6.6 Hz, 2H), 3.47−3.20 (m, 4H), 3.04 (dd,
J = 13.0, 10.7 Hz, 1H), 2.89 (d, J = 11.5 Hz, 1H), 1.79−1.43 (m, 6H),
1.36−1.23 (m, 8H), 0.90 (s, 18H), 0.11 (s, 3H), 0.08 (s, 3H), 0.05 (s,
6H) ppm; 13C NMR (75 MHz, CDCl3): δ 201.2, 172.3, 136.5, 129.4,
128.8, 127.2, 71.0, 68.5, 64.6, 63.2, 46.7, 41.1, 36.6, 36.5, 32.8, 32.0,
29.7, 29.4, 25.9, 25.8, 25.7, 25.5, 18.3, 17.9, −4.6, −4.7, −5.3 ppm;
Mass (ESI-MS) m/z: 690 [M + Na]+; HRMS (ESI): Calcd for
C34H61O4NNaS2Si2 [M + Na]+ 690.34727, found 690.34766. Minor
(17a): [α]2D4 = +32.03 (c 0.6, CHCl3); 1H NMR (300 MHz, CDCl3): δ
7.38−7.27 (m, 5H), 5.44−5.33 (m, 1H), 4.30−4.16 (m, 1H), 4.01−
3.88 (m, 1H), 3.60 (t, J = 6.6 Hz, 2H), 3.53 (d, J = 2.5 Hz, 1H), 3.48−
3.33 (m, 3H), 3.24 (dd, J = 13.2, 3.6 Hz, 1H), 3.04 (dd, J = 13.0, 10.7
Hz, 1H), 2.89 (d, J = 11.6 Hz, 1H), 1.79−1.42 (m, 6H), 1.38−1.22
(m, 8H), 0.89 (s, 18H), 0.09 (s, 3H), 0.08 (s, 3H), 0.05 (s, 6H) ppm;
13C NMR (125 MHz, CDCl3): δ 201.1, 172.9, 136.3, 129.3, 128.8,
127.1, 71.3, 68.3, 66.8, 63.1, 45.7, 42.8, 37.3, 36.6, 32.7, 31.9, 29.7,
29.3, 25.9, 25.8, 25.6, 24.6, 18.3, 17.9, −4.3, −4.7, −5.3 ppm; Mass
(ESI-MS) m/z: 690 [M + Na]+; HRMS (ESI): Calcd for
C34H61O4NNaS2Si2 [M + Na]+ 690.34727, found 690.34791.
1-((S)-4-Benzyl-2-thioxothiazolidin-3-yl)-2-((4S,6R)-6-(7-hydroxy-
heptyl)-2,2-dimethyl-1,3-dioxan-4-yl)ethanone (18). To a solution
of compound 17 (40 mg, 0.06 mmol) in 2 mL of THF was added
0.10 mL of 70% HF/pyridine solution. The solution was allowed
to stand at rt for 4 h, then the reaction was quenched by addition
of saturated NaHCO3 solution. After the layers were separated,
the aqueous layer was extracted with CH2Cl2 (2 × 5 mL). The
combined organic layers were dried over Na2SO4 and evaporated.
Which was used in the next reaction without further purification;
Rf = 0.6 (EtOAc).
To a solution of triol (0.06 mmol) in 1 mL of CH2Cl2 was added
3 drops of 2-methoxypropene and a catalytic amount of CSA at 0 °C.
The solution was stirred for 10 min at 0 °C, and quenched by addition
of saturated NaHCO3 solution. The mixture was extracted with
CH2Cl2, and the combined organic layers were dried over Na2SO4 and
evaporated. The residue was subjected to column chromatography
using ethyl acetate/hexane (30%) as eluent to provide 18 as a yellow
liquid (21 mg, 73%). Rf = 0.5 (50% EtOAc−hexane). [α]2D5 = +54.0
(c 0.25, CHCl3), IR (neat) υmax: 3418, 2929, 1694, 1261, 1217, 1163,
1042, 770 cm−1; 1H NMR (500 MHz, CDCl3): δ 7.38−7.32 (m, 2H),
7.31−7.27 (m, 3H), 5.38−5.32 (m, 1H), 4.47−4.40 (m, 1H), 3.81−
3.74 (m, 1H), 3.64 (t, J = 6.6 Hz, 2H), 3.45 (dd, J = 17.5, 8.6 Hz, 1H),
3.41−3.34 (m, 2H), 3.23 (dd, J = 13.2, 3.8 Hz, 1H), 3.03 (dd, J = 13.2,
10.7 Hz, 1H), 2.87 (d, J = 11.5 Hz, 1H), 1.70 (t, J = 7.8 Hz, 2H), 1.40
(s, 3H), 1.37−1.24 (m, 15H); 13C NMR (125 MHz, CDCl3): δ 201.3,
170.9, 136.5, 129.5, 128.9, 127.2, 100.6, 68.5, 66.6, 63.0, 44.7, 38.1,
36.6, 35.8, 32.8, 32.0, 29.5, 29.3, 25.7, 25.3, 24.7, 24.6; Mass (ESI-MS)
m/z: 502 [M + Na]+.
(7S,9R)-Ethyl 7,9,16-Tris(tert-butyldimethylsilyloxy)-2-methyl-3,5-
dioxohexadecanoate (8). To a stirred suspension of NaH (28 mg,
0.70 mmol, 60% w/w) in THF (3 mL) at 0 °C was added ethyl-2-
methylacetoacetate 6 (0.1 mL, 0.70 mmol); the resulting mixture was
stirred at 0 °C for 10 min before n-BuLi (0.43 mL, 1.6 M in hexanes,
0.70 mmol) was added dropwise at 0 °C. The solution was stirred for
10 min at 0 °C and cooled to −10 °C, and a solution of 19 (183 mg,
0.23 mmol) in THF (3 mL) was added dropwise via cannula. Then,
the reaction mixture was stirred at −10 °C for 10 min. The reaction
was quenched by addition of sat. aq. NH4Cl (5 mL) and allowed
to warm to rt. The mixture was extracted with Et2O (2 × 10 mL),
and the combined organic extracts were washed with brine (10 mL),
dried (Na2SO4), and concentrated in vacuo. Residual ethyl-2-
methylacetoacetate was removed under high vacuum, and the residue
was purified by column chromatography using ethyl acetate/hexane
(3%) as eluent to give a colorless liquid 8 (142 mg, 84%); Rf = 0.6
(5% EtOAc−hexane). IR (neat) υmax: 3441, 2932, 2857, 1741, 1607,
1253, 1096, 835, 771 cm−1; 1H NMR (500 MHz, CDCl3) δ 15.14 (bs,
1H, OH), 5.60 (d, J = 1.2 Hz, 1H), 4.22−4.10 (m, 2H), 3.74−3.68 (m,
1H), 3.59 (t, J = 6.6 Hz, 2H), 3.36 (qd, J = 7.2, 1.2 Hz, 1H), 2.53−2.44
(m, 1H), 2.39−2.27 (m, 1H), 1.68−1.56 (m, 2H), 1.54−1.47 (m, 2H),
1.46−1.40 (m, 1H), 1.38 (dd, J = 7.1, 1.2 Hz, 3H), 1.33−1.24 (m,
14H), 0.89 (s, 9H), 0.87 (s, 9H), 0.84 (s, 9H), 0.05 (s, 6H), 0.04 (s,
12H); 13C NMR (75 MHz, CDCl3): δ 193.7, 193.6, 188.8, 188.7,
170.7, 100.1, 99.9, 70.0, 69.3, 68.1, 68.0, 63.3, 61.3, 49.7, 49.6, 46.3,
45.8, 45.5, 37.7, 37.7, 32.8, 29.7, 29.5, 26.0, 25.9, 25.8, 25.0, 18.4, 18.0,
17.9, 14.1, 14.0, 13.9, −4.0, −4.3, −4.4, −4.4, −4.6, −5.3; Mass (ESI-
MS) m/z: 739 [M + Na]+; HRMS (ESI): Calcd for C37H76O7NaSi3
[M + Na]+ 739.47911, found 739.47994.
4-Hydroxy-3-methyl-6-((2S,4R)-2,4,11-tris(tert-butyldimethyl-
silyloxy)undecyl)-2H-pyran-2-one (20). To a stirred solution of
tricarbonyl 8 (50 mg, 0.07 mmol) in benzene (3 mL) was added DBU
(0.01 mL, 0.06 mmol) dropwise, and the resulting solution was heated
to 60 °C for 3 h. The reaction mixture was then cooled to 0 °C and
quenched by addition of 1 M HCl (2 mL). The mixture was extracted
with EtOAc (3 × 10 mL), and the combined organic extracts were
washed with brine (2 × 20 mL), dried (Na2SO4), and concentrated in
vacuo. The resulting residue was purified by column chromatography
using ethyl acetate/hexane (5%) as eluent to give α-pyrone 20 (13 mg,
25%) as a colorless liquid. Rf = 0.7 (40% EtOAc−hexane). [α]D24
=
+5.55 (c 1.0, CHCl3); IR (neat) υmax: 2931, 2857, 1675, 1586, 1412,
1
1255, 1056, 835, 774 cm−1; H NMR (500 MHz, CDCl3): δ 6.03 (s,
1H), 4.11−4.04 (m, 1H), 3.75−3.69 (m, 1H), 3.60 (t, J = 6.4 Hz, 2H),
2.65 (dd, J = 14.1, 5.0 Hz, 1H), 2.50 (dd, J = 14.2, 7.4 Hz, 1H), 1.95
(s, 3H), 1.72−1.56 (m, 2H), 1.55−1.39 (m, 4H), 1.36−1.22 (m, 8H),
0.89 (s, 9H), 0.85 (s, 9H), 0.82 (s, 9H), 0.05 (s, 6H), 0.03 (s, 6H),
0.02 (s, 6H) ppm; 13C NMR (125 MHz, CDCl3): δ 166.9, 164.8,
160.4, 102.1, 98.8, 70.0, 68.2, 63.5, 45.7, 42.6, 37.7, 32.8, 29.7, 29.4,
26.0, 25.9, 25.7, 25.7, 25.0, 18.4, 18.0, 17.9, 8.1, −4.0, −4.2, −4.5, −4.6,
−5.2 ppm; Mass (ESI-MS) m/z: 671 [M + H]+; HRMS (ESI): Calcd
for C35H71O6Si3 [M + H]+ 671.45530, found 671.45591.
(3S,5R)-1-((S)-4-Benzyl-2-thioxothiazolidin-3-yl)-3,5,12-tris(tert-
butyldimethylsilyloxy)dodecan-1-one (19). 2,6-Lutidine (0.06 mL,
0.48 mmol) was added to a solution of alcohol 17 (216 mg,
0.32 mmol) in anhydrous CH2Cl2 (5 mL), and the mixture was stirred
at 0 °C under N2. After 15 min, TBSOTf (0.1 mL, 0.42 mmol) was
added dropwise and the mixture was stirred at 0 °C for 5 min. The
reaction was quenched with H2O (5 mL), and the mixture was
extracted with CH2Cl2 (2 × 10 mL). The organic extract was washed
with brine (10 mL), dried (Na2SO4), filtered, and concentrated under
reduced pressure. The residue was purified by column chromato-
graphy using ethyl acetate/hexane (3%) as eluent to give a yellow
4-Hydroxy-3-methyl-6-((2S,4R)-2,4,11-trihydroxyundecyl)-2H-
pyran-2-one (2). To a solution of 20 (10 mg, 0.015 mmol) in dry
MeOH (2 mL) under an argon atmosphere was added 10-
camphorsulfonic acid (CSA) (1.7 mg, 0.007 mmol). The mixture
was stirred under argon for 1.5 h. The suspension was then quenched
with solid NaHCO3, filtered, and concentrated. The final mixture was
chromatographed on a silica gel column with MeOH/CHCl3 (10%)
as eluent, and final product 2 (3.7 mg, 75%) was obtained as a white
liquid 19 (235 mg, 93%); Rf = 0.5 (5% EtOAc−hexane). [α]D24
=
+68.79 (c 0.55, CHCl31); IR (neat) υmax: 2830, 2856, 1700, 1466, 1255,
1099, 835, 775 cm−1; H NMR (500 MHz, CDCl3): δ 7.37−7.32 (m,
2H), 7.31−7.27 (m, 3H), 5.29−5.21 (m, 1H), 4.40−4.32 (m, 1H),
3.78−3.69 (m, 1H), 3.60 (t, J = 6.7 Hz, 2H), 3.33 (dd, J = 11.4, 7.0 Hz,
1H), 3.29−3.17 (m, 2H), 3.04 (dd, J = 13.1, 10.8 Hz, 1H), 2.87 (d, J =
11.5 Hz, 1H), 1.76−1.58 (m, 2H), 1.54−1.38 (m, 4H), 1.37−1.24
(m, 8H), 0.90 (s, 9H), 0.89 (s, 9H), 0.85 (s, 9H), 0.10 (s, 3H),
solid. mp 120−122 °C; Rf = 0.5 (20% MeOH−CHCl3). [α]D25
=
+10.00 (c 0.05, MeOH), Lit.3 [α]2D5 = +20.0 (c 0.05, MeOH);
IR (KBr) υmax: 3430, 2926, 2854, 1659, 1615, 1555, 1407, 1258,
1
1059, 824, 754 cm−1; H NMR (700 MHz, CD3OD): δ 6.03 (s, 1H),
4.65 (bs, 1H, OH), 4.21−4.15 (m, 1H), 3.81−3.76 (m, 1H),
H
dx.doi.org/10.1021/jo5015382 | J. Org. Chem. XXXX, XXX, XXX−XXX