Synthesis of 12-oxo-PDA and OPC-8:0
A solution of the above methyl ester 19, TESCl (0.26 mL,
1.55 mmol), and imidazole (130 mg, 1.91 mmol) in DMF (8
mL) was stirred at room temperature for 1 h, cooled to 0 °C,
and diluted with hexane and saturated NaHCO3 with vigorous
stirring. The layers were separated, and the aqueous layer was
extracted with hexane three times. The combined extracts
were dried and concentrated to give a residue, which was
purified by chromatography (hexane/EtOAc) to afford silyl
diol 23, which was used for the next reaction without further
purification. An analytically pure sample was obtained by
chromatography: [R]25 +61 (c 0.89, CHCl3); IR (neat) 3350,
D
1056 cm-1; 1H NMR δ 0.99 (t, J ) 7.5 Hz, 3 H), 1.15-1.68 (m,
15 H), 1.96-2.53 (m, 7 H), 3.63 (t, J ) 6.5 Hz, 2 H), 4.51 (dd,
J ) 6, 2 Hz, 2 H), 5.33-5.57 (m, 2 H), 5.96 (ddd, J ) 6, 4, 2
Hz, 1 H), 6.23 (dd, J ) 6, 3 Hz, 1 H); 13C NMR δ 14.4, 20.9,
23.2, 25.9, 28.2, 29.5, 29.7, 30.0, 32.9, 33.7, 46.2, 46.3, 63.1,
76.7, 127.9, 132.0, 132.4, 141.7. Anal. Calcd for C18H32O2: C,
77.09; H, 11.50. Found: C, 77.20; H, 11.19.
ether 20 (398 mg, 82% from lactone 18): [R]29 -4.2 (c 0.836,
D
1
CHCl3); IR (neat) 1739, 1120, 701 cm-1; H NMR δ 0.55 (q, J
) 8 Hz, 6 H), 0.93 (t, J ) 8 Hz, 9 H), 1.05 (s, 9 H), 1.14-1.64
(m, 14 H), 2.31-2.64 (m, 4 H), 3.65 (t, J ) 6.5 Hz, 2 H), 3.67
(s, 3 H), 4.62 (dd, J ) 5, 2 Hz, 1 H), 5.80 (dm, J ) 6 Hz, 1 H),
6.04 (dd, J ) 6, 2 Hz, 1 H), 7.30-7.48 (m, 6 H), 7.61-7.75 (m,
4 H); 13C NMR δ 5.2, 7.0, 19.4, 26.0, 27.0, 28.0, 29.5, 29.7, 30.0,
30.3, 32.5, 32.7, 42.4, 45.9, 51.4, 64.1, 76.4, 127.5, 129.4, 132.5,
134.2, 135.5, 139.1, 174.2. Anal. Calcd for C38H60O4Si2: C,
71.64; H, 9.49. Found: C, 71.22; H, 9.40.
12-oxo-P DA (1). J ones reagent (4 M) was added to a
solution of the above crude diol 23 in acetone (2.5 mL) at 0 °C
until the color of the reagent persisted (17 drops). After 30
min at 0 °C, excess reagent was quenched by addition of
2-propanol, and the resulting mixture was filtered through a
pad of Celite with Et2O. The filtrate was washed with brine
several times until the solution became slightly acidic (pH 4).
The ethereal solution was dried (MgSO4) and concentrated to
give an oil, which was purified by chromatography (CH2Cl2/
acetone) to give 1 (60 mg, 53% from olefin 22). The 1H NMR
(300 MHz) spectrum for the major product (1) was consistent
with the reported data (400 MHz),1d and a ratio of 1 and the
Ald eh yd e 21. To a solution of methyl ester 20 (320 mg,
0.503 mmol) in CH2Cl2 (5 mL) was added DIBAL (0.70 mL,
0.93 M in hexane, 0.651 mmol) slowly at -78 °C. Reaction was
carried out at -78 °C for 1 h and quenched by addition of
MeOH (0.26 mL, 6.5 mmol). After 10 min at -78 °C, H2O (0.23
mL, 13 mmol) diluted with THF (0.23 mL) was added. The
cooling bath was removed, NaF (547 mg, 13 mmol) was added
to the solution, and the mixture was stirred vigorously for 30
min. The resulting mixture was filtered through a pad of Celite
with EtOAc. Concentration of the filtrate gave a residue, which
was purified by chromatography (hexane/EtOAc) to afford
epimer 24 was >95:<5 from the spectrum: [R]29 +127 (c
D
0.496, CHCl3) (lit.5a [R]25 +104.0 (c 9.5, CHCl3)); IR (neat)
D
3100, 1707 cm-1
;
13C NMR δ 14.2, 20.9, 23.9, 24.8, 27.7, 29.1,
29.2, 29.7, 30.9, 34.1, 44.4, 50.0, 126.9, 132.4, 132.9, 167.2,
179.4, 210.9. Anal. Calcd for C18H28O3: C, 73.93; H, 9.65.
Found: C, 73.81; H, 9.61.
La cton e 41. To a solution of iodo-lactone 17 (891 mg, 1.40
mmol) in benzene (5 mL) were added Bu3SnH (1.13 mL, 4.31
mmol) and AIBN (23 mg, 0.14 mmol). After 1 h of reflux, the
reaction was quenched by addition of NaF. The slurry was
stirred at room temperature for 30 min, and filtered through
a pad of Celite with EtOAc. The filtrate was concentrated, and
a residue was purified by chromatography (hexane/EtOAc) to
afford 41 (668 mg, 94%): [R]30D -6.5 (c 0.98, CHCl3); IR (neat)
aldehyde 21 (263 mg, 86%): IR (neat) 1726, 1112, 701 cm-1
;
1H NMR δ 0.55 (q, J ) 8 Hz, 6 H), 0.94 (t, J ) 8 Hz, 9 H), 1.05
(s, 9 H), 1.14-1.63 (m, 14 H), 2.38 (dd, J ) 15, 4 Hz, 1 H),
2.48-2.59 (m, 1 H), 2.61-2.79 (m, 2 H), 3.65 (t, J ) 6.5 Hz, 2
H), 4.68 (dm, J ) 6 Hz, 1 H), 7.31-7.49 (m, 6 H), 7.63-7.73
(m, 4 H), 9.87 (t, J ) 1 Hz, 1 H); 13C NMR δ 5.2, 7.1, 19.4,
26.0, 27.0, 28.1, 29.5, 29.7, 30.0, 32.3, 32.7, 40.2, 41.7, 45.9,
64.1, 76.8, 127.5, 129.4, 132.6, 134.2, 135.6, 138.1, 202.8.
1
1772, 1111 cm-1; H NMR δ 1.05 (s, 9 H), 1.16-2.10 (m, 19
H), 2.38-2.57 (m, 2 H), 2.86-3.00 (m, 1 H), 3.66 (t, J ) 6.5
Hz, 2 H), 5.03 (t, J ) 6 Hz, 1 H), 7.32-7.48 (m, 6 H), 7.60-
7.74 (m, 4 H); 13C NMR δ 19.4, 25.9, 27.1, 28.7, 28.9, 29.1,
29.5, 29.7, 29.9, 30.8, 32.7, 33.2, 40.6, 42.9, 64.1, 86.2, 127.6,
129.5, 134.2, 135.6, 177.9. Anal. Calcd for C31H44O3Si: C, 75.56;
H, 9.00. Found: C, 75.58; H, 9.17.
Meth yl Ester 42. According to the procedure for the
synthesis of 20, a mixture of lactone 41 (370 mg, 0.727 mmol)
in THF (5.1 mL), MeOH (1.7 mL), and H2O (1.7 mL) was
stirred with LiOH‚H2O (178 mg, 4.24 mmol) at room temper-
ature for 1 h, cooled to 0 °C, diluted with saturated NH4Cl
and Et2O, acidified to pH ca. 4 with 1 N HCl, and extracted
with Et2O. The extracts were combined, cooled to 0 °C, and
treated with CH2N2 to give the hydroxyl methyl ester after
short-column chromatography by using Et2O as an eluent.
A solution of the above ester, TESCl (0.28 mL, 1.69 mmol),
and imidazole (144 mg, 2.12 mmol) in DMF (8 mL) was stirred
at room temperature for 1 h to afford silyl ester 42 (358 mg,
75% from lactone 41) after chromatography (hexane/EtOAc):
[R]26D -0.5 (c 0.75, CHCl3); IR (neat) 1740, 1112 cm-1; 1H NMR
δ 0.55 (q, J ) 8 Hz, 6 H), 0.94 (t, J ) 8 Hz, 9 H), 1.05 (s, 9 H),
1.00-1.96 (m, 19 H), 2.21 (dd, J ) 15, 6 Hz, 1 H), 2.33-2.44
(m, 1 H), 2.47 (dd, J ) 15, 7.5 Hz, 1 H), 3.65 (s, 3 H), 3.65 (t,
J ) 6.5 Hz, 2 H), 4.15-4.26 (m, 1 H), 7.28-7.48 (m, 6 H), 7.63-
7.71 (m, 4 H); 13C NMR δ 5.0, 7.0, 19.4, 26.0, 27.0, 28.2, 28.6,
29.5, 29.6, 29.8, 30.0, 31.8, 32.8, 32.9, 39.7, 43.9, 51.4, 64.1,
75.1, 127.5, 129.4, 134.2, 135.6, 174.6. Anal. Calcd for C38H62O4-
Si2: C, 71.42; H, 9.78. Found: C, 71.46; H, 9.94.
Olefin 22. To a suspension of n-propyltriphenylphosphon-
ium bromide (720 mg, 1.87 mmol) in THF (3 mL) was added
NaN(TMS)2 (1.80 mL, 1.0 M in THF, 1.80 mmol) at 0 °C. The
mixture was stirred at room temperature for 40 min and cooled
to 0 °C before addition of DMF (0.54 mL, 6.97 mmol) and a
solution of aldehyde 21 (263 mg, 0.434 mmol) in THF (2 mL).
Reaction was carried out at room temperature for 1 h and
quenched by addition of hexane and saturated NH4Cl. The
layers were separated, and the aqueous layer was extracted
with hexane three times. The combined extracts were dried
and concentrated to give an oil. To remove PPh3 residue, the
oil was diluted with THF (4 mL) and treated with 35% H2O2
(0.49 mL, 5.6 mmol) at 0 °C for 30 min. Hexane and brine were
added to the mixture and the layers were separated. The
aqueous layer was extracted with hexane three times. The
combined extracts were dried and concentrated to leave a
residue, which was purified by chromatography (hexane/
EtOAc) to afford olefin 22 (238 mg, 87%): [R]27D +1.2 (c 0.724,
1
CHCl3); IR (neat) 1112, 701 cm-1; H NMR δ 0.57 (q, J ) 8
Hz, 6 H), 0.95 (q, J ) 8 Hz, 9 H), 1.05 (s, 9 H), 0.86-1.62 (m,
17 H), 1.88-2.48 (m, 6 H), 3.65 (t, J ) 6.5 Hz, 2 H), 4.50 (dd,
J ) 6, 3 Hz, 1 H), 5.26-5.58 (m, 2 H), 5.78-5.92 (m, 1 H),
6.12 (dd, J ) 6, 3 Hz, 1 H), 7.33-7.47 (m, 6 H), 7.64-7.72 (m,
4 H); 13C NMR δ 5.4, 7.2, 14.5, 19.4, 21.0, 23.4, 26.0, 27.0, 28.2,
29.6, 29.8, 30.2, 32.6, 32.8, 46.2, 47.4, 64.1, 76.4, 127.5, 128.7,
129.5, 131.6, 132.7, 134.2, 135.6, 140.2. Anal. Calcd for
C
40H64O2Si2: C, 75.79; H, 10.23. Found: C, 75.88; H, 10.19.
Diol 23. A mixture of olefin 22 (245 mg, 0.387 mmol), Bu4-
NF (1.93 mL, 1.0 M in THF, 1.93 mmol), 4A molecular sieves
(128 mg), and THF (4 mL) was stirred at 55 °C for 1 h, cooled
to 0 °C, and diluted with EtOAc and saturated NH4Cl with
stirring. The resulting mixture was filtered through a pad of
Celite with EtOAc, and the filtrates were separated. The
aqueous layer was extracted with EtOAc three times, and the
combined extracts were dried and concentrated to give crude
Olefin 44. According to the procedure for the synthesis of
olefin 22, ester 42 (84 mg, 0.13 mmol) in CH2Cl2 (1.3 mL) was
submitted to reduction with DIBAL (0.17 mL, 0.93 M in
hexane, 0.16 mmol) at -78 °C for 50 min to produce aldehyde
43 (61 mg, 77%) after chromatography (hexane/EtOAc): IR
(neat) 1726, 1112 cm-1 1H NMR δ 0.55 (q, J ) 8 Hz, 6 H),
;
0.93 (t, J ) 8 Hz, 9 H), 1.05 (s, 9 H), 1.13-2.26 (m, 20 H),
J . Org. Chem, Vol. 68, No. 20, 2003 7831