K. Mori, S. Sano, Y. Yokoyama, M. Bando, M. Kido
FULL PAPER
This was stirred vigorously at room temp. for 10 h and then diluted
with CH2Cl2. The organic layer was separated and aqueous layer
(2S,3R,1ЈS,2ЈS)-2,3-Dihydro-6-[2-hydroxy-1-methybutyl]-2,3,5-
trimethyl-4H-pyran-4-one (2) (Stegobiol): To a solution of 16 (480
was extracted with CH2Cl2. The combined organic layers were mg, 1.39 mmol) in CH3CN was added 46% hydrofluoric acid (152
dried with magnesium sulfate and concentrated in vacuo. The resi- µl, 3.48 mmol) at 0°C. The mixture was stirred at 0Ϫ4°C for 14 h,
due was diluted with diethyl ether, filtered through Celite and con- then diluted with diethyl ether, and a satd. aqueous sodium hydro-
centrated in vacuo. The residue was chromatographed on silica gel gen carbonate solution, and separated. The aqueous layer was ex-
(15 g, hexane/diethyl ether, 20:1) to give 386 mg (84%) of 14 as a tracted with diethyl ether. The combined organic layers were
colorless oil. This was immediately used in the next step without washed with a satd. sodium hydrogen carbonate solution, brine
23
24
further purification, nD ϭ 1.4422. Ϫ [α]D ϭ ϩ10.0 (c ϭ 1.11,
CHCl3). Ϫ IR (film): ν˜max ϭ 3000 cmϪ1 (m, br. CO2 H), 1710 (s, due was purified by preparative TLC to give 150 mg (47%) of stego-
CϭO), 1055 (m, CϪO), 1015 (m, CϪO). Ϫ 1H NMR (90 MHz,
biol 2 as an oil and a mixture of its stereoisomer (61 mg, 19%)
dried with magnesium sulfate and concentrated in vacuo. The resi-
CDCl3): δ ϭ 0.05 [s, 6 H, Si(CH3)2], 0.87 (m, 3 H, 5-H3), 0.90 [s, which could not be identified. The oily stegobiol 2 crystallized
9 H, SiC(CH3)3], 1.20 (d, 3 H, J ϭ 7.6 Hz, 2-CH3), 1.58 (br. quint., when left to stand in a refrigerator (0Ϫ4°C). The crude crystalline
2 H, J ϭ 6.9 Hz, 4-H2), 2.68 (dq, 1 H, J ϭ 4.8, JЈ ϭ 7.6 Hz, 2-H),
3.80 (q, 1 H, J ϭ 4.8, JЈ ϭ 6.2 Hz, 3-H).
stegobiol was recrysytallized from pentane/diethyl ether (1:1) to
give pure crystalline stegobiol
2 (117 mg) as prisms, m.p.
24
73.0Ϫ74.0°C [ref.[12] m.p. 73Ϫ74.2°C]. Ϫ [α]D ϭ Ϫ108.2 (c ϭ
(1ЈS,2ЈR,2S,3S)-1Ј,2Ј-Dimethyl-3Ј-oxopentyl 3-tert-Butyldimeth-
ylsilyloxy-2-methylpentanoate (15): 2,6-Dichlorobenzoyl chloride
(230 mg, 1.10 mmol) was added to a mixture of 14 (270 mg, 1.10
mmol) and triethylamine (122 mg, 1.21 mmol) in dry THF (7 ml)
under argon. The mixture was stirred for 11 h at room temp.. After
the removal of Et3NиHCl by filtration, the filtrate was concentrated
under N2, and the residue was dissolved in dry benzene (15 ml).
To this solution were added a solution of 4 (186 mg, 1.43 mmol)
in dry benzene (1 ml) and DMAP (148 mg, 1.21 mmol) in dry
benzene (1 ml) at 0°C under argon. The resulting mixture was
stirred for 3 h at 0°C, then diluted with diethyl ether, washed with
dil. hydrochrolic acid, water, a satd. aqueous sodium hydrogen car-
bonate solution, brine, dried with magnesium sulfate and concen-
trated in vacuo. The residue was purified by chromatography on
silica gel (10 g, hexane/diethyl ether, 40:1) to give (357 mg, 90%) of
15 as a colorless oil. This was immediately used in the next step
without further purification, nD24 ϭ 1.4455. Ϫ [α]D24 ϭ ϩ1.50 (c ϭ
1.10, CHCl3). Ϫ IR (film): ν˜max ϭ 1735 cmϪ1 (s, CϭO), 1720 (s,
CϭO), 1050 (m, CϪO), 1015 (m, CϪO). Ϫ 1H NMR (90 MHz,
CDCl3): δ ϭ 0.05 [br. s, 6 H, Si(CH3)2], 0.63Ϫ1.60 (m, 17 H, 2-,
19
0.09, CHCl3) [ref.[7] [α]D ϭ Ϫ110±6 (c ϭ 0.42, CHCl3), ref.[12]
[α]D25 ϭ Ϫ118.7±7 (c ϭ 0.107, CHCl3)]. Ϫ IR (KBr): ν˜max ϭ 3500
cmϪ1 (m, ϪOH), 3000 (m), 2950 (m), 2900 (m), 1640 (s, CϭO),
1610 (s, CϭO), 1460 (w), 1450(w), 1395 (m), 1380 (m), 1360 (m),
1340 (m), 1320 (w), 1300 (w), 1285 (w), 1240 (w), 1200 (m), 1150
(m), 1135 (w), 1112 (m), 1110 (w), 1080 (w), 1040 (w), 1030 (w),
1005 (w), 1000 (w), 980 (w), 970 (w), 940 (w), 920 (w), 870 (w), 840
(w), 830 (w), 780 (w), 710 (w). Ϫ 1H NMR (300 MHz, CDCl3):
δ ϭ 1.00 (t, 3 H, J ϭ 7.4 Hz, 4Ј-H3), 1.04 (d, 3 H, J ϭ 7.4 Hz, 1Ј-
CH3), 1.18 (d, 3 H, J ϭ 7.1 Hz, 3-CH3), 1.33 (d, 3 H, J ϭ 6.6 Hz,
2-CH3), 1.37Ϫ1.48 (m, 1 H, 3Ј-Ha), 1.52Ϫ1.64 (m, 1 H, 3Ј-Hb),
1.75 (s, 3 H, 5ϪCH3), 1.91 (d, 1 H, J ϭ 7.4 Hz, 2Ј-OH), 2.38 (dq,
1 H, J ϭ 3.5, JЈ ϭ 7.3 Hz, 1Ј-H), 2.86 (dq, 1 H, J ϭ 6.9, JЈ ϭ 7.0
Hz, 3-H), 3.53Ϫ3.63 (m, 1 H, 2Ј-H), 4.49 (dq, 1 H, J ϭ 6.5, JЈ ϭ
3.6 Hz, 2-H). Ϫ 13C NMR (75.5 MHz, CDCl3): δ ϭ 9.2, 9.4, 10.1,
14.7, 15.9, 28.3, 40.8, 43.7, 75.3, 76.6, 109.3, 172.7, 197.1. These
spectral data were in good accord with those reported in refs[7][12]
.
Ϫ C13H22O3 (226.32) calcd. C 68.99, H 9.80, found C 68.74, H 9.57.
(2S,3R,1ЈR)-2,3-Dihydro-6-[1-methyl-2-oxobutyl]-2,3,5-
1Ј-, 2Ј-CH3, 4-H2, 5-,5Ј-H3), 0.87 [s, 9 H, SiC(CH3)3], 2.35Ϫ2.90 trimethyl-4H-pyran-4-one (1) (Stegobinone). Ϫ (i) Dess-Martin Oxi-
(m, 3 H, 2, 2Ј-CH3), 2.50 (quint., 2 H, J ϭ 6.7 Hz, 4Ј-H2), 3.90 (q, dation: Preparation of pyridine-buffered Dess-Martin periodinane
1 H, J ϭ 5.1 Hz, 3-H), 5.13 (quint., 1 H, J ϭ 6.2 Hz, 1Ј-CH). These stock solution: Dess-Martin periodinane (140 mg, 0.331 mmol) was
spectral data were in good accord with those reported in ref.[7]
.
added to an argon-purged flask (glove bag). The solid was taken
up in CH2Cl2 (5.4 ml) and pyridine (160 µl, 1.98 mmol) was added.
This stock solution was employed in the oxidation immediately. To
a solution of stegobiol 2 (14 mg, 0.062 mmol) in CH2Cl2 (1 ml)
was added freshly prepared periodinane stock solution (2.0 ml) in
one portion. After 25 min, this solution was diluted with diethyl
ether and quenched by introducing a satd. aqueous sodium hydro-
gen carbonate solution/sodium bisulfate (1:1, 5 ml), and the re-
sulting mixture was stirred for 5 min. Upon further dilution with
diethyl ether, the mixture was washed with a satd. sodium hydrogen
carbonate solution, brine, dried with magnesium sulfate and con-
centrated in vacuo. The residue was purified by chromatography
on silica gel (1g, pentane/diethyl ether, 5:1) to give 14 mg (quant.)
of (2S,3R,1ЈR)-stegobinone (1) as an oil, which crystallized under
Ϫ78°C in a freezer. This was recrystallized from pentane as de-
scribed in ref.[12] to give pure crystalline stegobinone as prisms.
(2S,3R,1ЈS,2ЈS)-2,3-Dihydro-6-[1Ј-methyl-2-(tert-butyldimeth-
ylsilyloxybutyl]-4H-pyran-4-one (16): A 0.5 solution of TiCl4 in
CH2Cl2 (21.5 ml, 10.8 mmol) was added dropwise at Ϫ78°C to a
solution of 15 (770 mg, 2.15 mmol) and ethyldiisopropylamine
(2.68 ml, 17.2 mmol) in CH2Cl2 (92 ml). The mixture was stirred
at Ϫ78°C for 3 h, then allowed to warm up to Ϫ10°C over 2 h and
stirred between Ϫ10°C and Ϫ20°C for 2 d. Then to the mixture
was added a satd. aqueous NH4Cl solution, diluted with diethyl
ether, and the organic layer was separated. The aqueous layer was
extracted with diethyl ether. The combined organic layers were
washed with water (twice), a satd. aqueous sodium hydrogen car-
bonate solution, brine, dried with magnesium sulfate and concen-
trated in vacuo. The residue was purified by chromatography on
silica gel (20 g, hexane/diethyl ether, 30:1) to give 480 mg (66%) of
16 as an oil. This was immediately used in the next step without
24
24
further purification, nD ϭ 1.4805. Ϫ [α]D ϭ ϩ66.3 (c ϭ 1.10,
(ii) TPAPϪNMO: To a solution of stegobiol 2 (10 mg, 0.044
mmol) in CH2Cl2 (0.6 ml) was added tetrapropylammoinum per-
CHCl3). Ϫ IR (film): ν˜max ϭ 1665 cmϪ1 (vs, CϭO), 1605 (s, Cϭ
C), 1140 (m, SiϪMe), 1115 (m, SiϪMe), 1030 (m, CϪO). Ϫ 1H ruthenate (TPAP) (84.7 mg, 0.013 mmol), N-methylmorpholine N-
˚
NMR (90 MHz, CDCl3): δ ϭ Ϫ0.2 (s, 3 H, Si-CH3), 0.2 (s, 3 H, oxide (21 mg, 0.18 mmol) and powdered molecular sieves (4 A) (0.1
Si-CH3), 0.82 [s, 9 H, SiC(CH3)] 3, 0.76Ϫ1.1 (m, 6 H, 1Ј-, 4Ј-CH),
g). The mixture was stirred at room temp. for 28 h, diluted with
1.1 (d, 3 H, J ϭ 7.5 Hz, 3-CH3), 1.33 (d, 3 H, J ϭ 7.2 Hz, 2-CH3), diethyl ether, and purified by preparative TLC to give the recovered
1.38Ϫ1.64 (m, 2 H, 3Ј-H2), 1.75 (s, 3 H, 5-CH3) 2.38 (dq, 1 H, J ϭ 2 (2 mg, 20%) and 7 mg (89% based on the comsumed 2) of stegobi-
3.2, JЈ ϭ 7.2 Hz, 1Ј-H), 2.86 (m, 1 H, 3-H), 3.74Ϫ4.00 (m, 1H, 2Ј-
H), 4.49 (dq, 1 H, J ϭ 4.0, JЈ ϭ 6.4 Hz, 2-H).
none 1 as an oil. This was also recrystallized in the same manner
as described above.
1140
Eur. J. Org. Chem. 1998, 1135Ϫ1141