Journal of Natural Products
Note
pressure. A solution of 0.1 M HIO4 in H2O (3 mL, 0.3 mmol) was
added to the resultant residue again, and the reaction mixture was
stirred at rt for 30 min. After cooling to 0 °C, a solution of 1 M NaBH4
in H2O (1.2 mL, 1.2 mmol) was added. After stirring for 30 min, the
reaction was quenched with two drops of AcOH, and the reaction
mixture was concentrated under reduced pressure. The resultant
mixture was roughly purified by silica gel column chromatography
(CHCl3/MeOH = 10:1 to 2:1) to give crude 12 (19.3 mg) as a
colorless syrup, which was used for the next reaction without further
purification.
applicable to other amphidinol congeners to determine the
absolute configuration of the THP rings.
EXPERIMENTAL SECTION
■
General Experimental Procedures. Optical rotations were
recorded on a JASCO P-1010 polarimeter. IR spectra were recorded
1
on a JASCO FT-IR 4100ST. H and 13C NMR spectra were recorded
on JEOL JNM-ECA600 spectrometer. Chemical shifts are reported in
ppm from reference to internal residual solvent [1H NMR, CHCl3
1
(7.24); 13C NMR, CDCl3 (77.0) or H NMR, CHD2OD (3.30); 13C
Compound 7a. To a solution of (R)-MTPA acid (100 mg, 0.426
mmol) in hexane (1 mL) were added oxalyl chloride (5.6 μL, 0.64
mmol) and DMF (6.6 μL, 86 μmol). After stirring for 1 h at rt, the
solution was concentrated under reduced pressure to give (S)-
MTPACl.10 (S)-MTPACl (35.0 mg, 139 μmol) was added to a
solution of the crude 12 (9.7 mg) in pyridine (346 μL). After stirring
for 1 h at rt, the reaction mixture was diluted with hexane and
quenched with saturated aqueous NaHCO3. The aqueous layer was
extracted with hexane three times, and the combined organic extracts
were dried over anhydrous Na2SO4, filtered, and concentrated under
reduced pressure. Purification by preparative TLC (hexane/EtOAc =
3:1) afforded (R)-MTPA ester 7a (3.9 mg, 3.7 μmol) in 16% yield in
five steps as a colorless syrup: [α]26D +45.8 (c 0.20, CHCl3); IR (film)
ν 2953, 2921, 2850, 1751, 1452, 1271, 1240, 1168, 1121, 1022, 719
cm−1; 1H NMR (600 MHz, CDCl3) δ 7.47−7.41 (m, 8H), 7.39−7.31
(m, 12H), 4.27 (m, 1H), 4.26 (m, 1H), 4.25 (m, 1H), 4.17 (dd, J =
12.0, 4.8 Hz, 1H), 4.13 (ddd, J = 10.8, 5.4, 2.4 Hz, 1H), 4.01 (dd, J =
11.4, 4.2 Hz, 1H), 3.96 (dd, J = 11.4, 5.4 Hz, 1H), 3.91 (dd, J = 11.4,
6.0 Hz, 1H), 3.57 (m, 1H), 3.48 (m, 1H), 3.47 (s, 3H), 3.46 (s, 6H),
3.45 (s, 3H), 1.71 (m, 1H), 1.63 (m, 1H); 13C NMR (150 MHz,
CDCl3) δ 166.3, 166.2, 166.1, 132.1, 132.0, 129.9, 128.6, 127.3, 123.3
(q, J = 287.3 Hz), 123.2 (q, J = 287.1 Hz), 84.66 (q, J = 28.8 Hz),
84.62 (q, J = 28.8 Hz), 84.58 (q, J = 28.2 Hz), 73.9, 67.4, 64.1, 64.0,
63.9, 61.9, 55.4, 55.44, 55.38, 55.30, 30.9; HRMS (ESI, positive) m/z
[M + Na]+ calcd for C47H44O13F12Na, 1067.2483, found 1067.2481.
Compound 7b. To a solution of (S)-MTPA acid (100 mg, 0.426
mmol) in hexane (1 mL) were added oxalyl chloride (5.6 μL, 0.64
mmol) and DMF (6.6 μL, 86 μmol). After stirring for 1 h at rt, the
solution was concentrated under reduced pressure to give (R)-
MTPACl.10 (R)-MTPACl (35.0 mg, 139 μmol) was added to a
solution of the crude 12 (9.7 mg) in pyridine (346 μL). After stirring
for 1 h at rt, the reaction mixture was diluted with hexane and
quenched with saturated aqueous NaHCO3. The aqueous layer was
extracted with hexane three times, and the combined organic extracts
were dried over anhydrous Na2SO4, filtered, and concentrated under
reduced pressure. Purification by preparative TLC (hexane/EtOAc =
3:1) afforded (S)-MTPA ester 7b (3.6 mg, 3.4 μmol) in 15% yield in
five steps as a colorless syrup: [α]26D −42.7 (c 0.20, CHCl3); IR (film)
ν 2953, 2922, 2849, 1751, 1452, 1270, 1241, 1168, 1121, 1023, 719
cm−1; 1H NMR (600 MHz, CDCl3) δ 7.48−7.42 (m, 8H), 7.39−7.32
(m, 12H), 4.33 (ddd, J = 10.8, 5.4, 5.4 Hz, 1H), 4.23 (dd, J = 11.4, 4.2
Hz, 1H), 4.21 (dd, J = 12.0, 4.8 Hz, 1H), 4.18 (dd, J = 12.0, 6.0 Hz,
1H), 4.07 (m, 1H), 4.06 (m, 1H), 3.99 (dd, J = 9.6, 4.8 Hz, 1H), 3.97
(dd, J = 9.6, 5.4 Hz, 1H), 3.72 (dddd, J = 4.8, 4.8, 4.8, 4.8 Hz, 1H),
3.53 (m, 1H), 3.48 (s, 3H), 3.46 (s, 3H), 3.454 (s, 3H), 3.450 (s, 3H),
1.73 (m, 1H), 1.65 (m, 1H); 13C NMR (150 MHz, CDCl3) δ 166.22,
166.18, 166.1, 165.9, 132.1, 131.9, 129.8, 129.7, 128.5, 127.3, 127.2,
123.3 (q, J = 287.3 Hz), 123.2 (q, J = 287.3 Hz), 84.7 (q, J = 28.8 Hz),
84.5 (q, J = 28.8 Hz), 73.7, 73.3, 67.2, 63.9, 63.5, 61.7, 55.3, 30.9;
HRMS (ESI, positive) m/z 1067.2485 [M + Na]+ (calcd for
C47H44O13F12Na, 1067.2483).
NMR, CD3OD (49.0)]. High-resolution mass spectra (HRMS) were
recorded on a Burker micrOTOFfocus under ESI-TOF conditions. All
reactions sensitive to air or moisture were performed under an argon
atmosphere with dry glassware unless otherwise noted. The
dehydrated solvents, tetrahydrofuran (THF) and pyridine, were
purchased from Kanto Chemical Co. Inc. or Wako Pure Chemical
Industries Ltd. and were used without further dehydration. All other
chemicals were obtained from local venders and used as supplied.
Thin-layer chromatography (TLC) of E. Merck silica gel 60 F254
precoated plates (0.25 mm thickness) was used for the reaction
analyses. For column chromatography, Kanto silica gel 60N (spherical,
neutral, 100−210 μm) was used. For preparative TLC, E. Merck silica
gel 60 F254 precoated plates (0.25 mm thickness, 10 cm × 10 cm)
were used.
Compound 9. Raney nickel W-2 in EtOH (4 mL) was added to a
solution of benzyl ether 8 (800 mg, 744 μmol) in EtOAc (2 mL) at
room temperature (rt) and stirred at 35 °C for 48 h under a hydrogen
atmosphere. The reaction mixture was filtered through a pad of Celite,
and the residue was washed with EtOAc. The combined filtrate was
concentrated under reduced pressure. Purification by silica gel column
chromatography (hexane/EtOAc = 10:1) afforded 9 (740 mg, quant)
as a colorless syrup: [α]22 +20.6 (c 0.65, CHCl3); IR (film) ν 3477,
D
1
2953, 2929, 2885, 2857, 1251, 1105, 835, 774 cm−1; H NMR (600
MHz, CDCl3) δ 7.20 (d, J = 7.8 Hz, 2H), 6.84 (d, J = 7.8 Hz, 2H),
4.41 (s, 2H), 4.02 (d, J = 10.2 Hz, 1H), 3.98 (brs, 1H), 3.96 (dd, J =
7.8, 6.0 Hz, 1H), 3.92 (m, 1H), 3.80−3.74 (m, 3H), 3.79 (s, 3H), 3.62
(brd, J = 12.6 Hz, 1H), 3.49 (m, 1H), 3.46 (dd, J = 8.4, 7.8 Hz, 1H),
3.31 (dd, J = 7.8, 5.4 Hz, 1H), 2.62 (brs, 1H), 2.05 (ddd, J = 12.0, 12.0,
12.0 Hz, 1H), 1.50 (brd, J = 12.0 Hz, 1H), 0.879 (s, 9H), 0.875 (s,
9H), 0.87 (s, 9H), 0.84 (s, 9H), 0.83 (s, 9H), 0.06 (s, 15H), 0.04 (s,
3H), 0.03 (s, 6H), 0.006 (s, 3H), −0.03 (s, 3H); 13C NMR (150 MHz,
CDCl3) δ 159.2, 130.4, 129.1, 113.7, 79.0, 73.2, 72.7, 72.2, 70.4, 69.8,
69.2, 69.2, 68.6, 63.5, 55.3, 28.4, 26.02, 25.99, 25.8, 25.8, 25.7, 18.4,
18.13, 18.13, 18.11, 17.9, −3.4, −4.0, −4.0, −4.27, −4.29, −4.5, −4.7,
−4.8, −4.96, −5.03; HRMS (ESI, positive) m/z 981.5929 [M + Na]+
(calcd for C48H98O9Si5Na, 981.5949).
Compound 10. A solution of 1 M TBAF in THF (1.6 mL, 1.6
mmol) was added to a solution of 9 (102.4 mg, 106.7 μmol) in THF
(4 mL) at 0 °C. After stirring at rt for 2 h, the reaction mixture was
concentrated under reduced pressure. The residue was purified by
flash silica gel column chromatography (CHCl3/MeOH = 3:1),
followed by preparative TLC (CHCl3/MeOH = 3:1) to afford 10
(33.7 mg) in 81% yield as a colorless syrup: [α]25 −8.5 (c 0.1,
D
MeOH); IR (film) ν 3322, 2959, 2927, 2874, 1514, 1465, 1371, 1247,
1074 cm−1; 1H NMR (600 MHz, CD3OD) δ 7.26 (d, J = 9.0 Hz, 2H),
6.88 (d, J = 9.0 Hz, 2H), 4.48 (s, 2H), 4.02 (brt, J = 2.4 Hz, 1H), 3.98
(ddd, J = 6.0, 6.0, 1.8 Hz, 1H), 3.95 (m, 1H), 3.93 (m, 1H), 3.87 (dd, J
= 10.2, 1.2 Hz, 1H), 3.77 (s, 3H), 3.65−3.60 (m, 2H), 3.59−3.50 (m,
4H), 1.91 (ddd, J = 12.0, 12.0, 12.0 Hz, 1H), 1.59 (ddd, J = 12.6, 4.8,
3.0 Hz, 1H); 13C NMR (150 MHz, CD3OD) δ 160.8, 131.7, 130.5,
114.8, 78.3, 75.2, 74.0, 72.3, 72.2, 69.1, 68.9, 68.6, 67.1, 64.1, 55.7,
31.2; HRMS (ESI, positive) m/z 411.1624 [M + Na]+ (calcd for
C18H28O9Na, 411.1626).
Compound 6. A solution of 0.1 M HIO4 in H2O (20 μL, 2 μmol)
was added to AM3 (0.125 μmol, estimated by 1H NMR using DMF as
an internal standard) in a vial, and the reaction mixture was stirred at rt
for 30 min. After cooling to 0 °C, a solution of 1 M NaBH4 in H2O (8
μL, 8 μmol) was added. After stirring for 30 min, the reaction was
quenched with one drop of AcOH, and the reaction mixture was
concentrated under reduced pressure. A solution of 0.1 M HIO4 in
H2O (20 μL, 2 μmol) was added to the resultant residue again, and the
reaction mixture was stirred at rt for 30 min. After cooling to 0 °C, a
Compound 12. A solution of 0.1 M HIO4 in H2O (3 mL, 300
μmol) was added to compound 10 (18.5 mg, 47.6 μmol) in a flask,
and the reaction mixture was stirred at rt for 30 min. After cooling to 0
°C, a solution of 1 M NaBH4 in H2O (1.2 mL, 1.2 mmol) was added.
After stirring for 30 min, the reaction was quenched with two drops of
AcOH, and the reaction mixture was concentrated under reduced
2005
dx.doi.org/10.1021/np300604w | J. Nat. Prod. 2012, 75, 2003−2006