amine (10.5 cm3, 75 mmol) in dry THF (100 cm3) under N2 at
0 ЊC was added n-BuLi (1.6 M in hexanes, 45 cm3, 71.9 mmol),
with the suspension then cooled to Ϫ78 ЊC this being held
for 30 min. To this was sequentially added dropwise 4-O-tert-
butyldimethylsilyloxypropiophenone (27) (16.5 g, 62.4 mmol)
in THF (50 cm3), followed by copper() trifluoromethane-
sulfonate (25 g, 75 mmol) in acetonitrile (60 cm3). Following
stirring for 9 h, the reaction mixture was quenched with satur-
ated NH4Cl solution (100 cm3) and extracted with ethyl acetate
(3 × 100 cm3), with the corresponding organic solubles washed
successively with water (3 × 50 cm3) and brine solution (3 ×
50 cm3). The organic solubles were dried (Na2SO4) and evapor-
ated to dryness in vacuo, with the residue reconstituted in a
minimum amount of chloroform and subjected to silica gel
column chromatography (eluted with hexanes–EtOAc, 95 : 5)
to afford ( )-(8S,8ЈS)-8,8Ј-dimethyl-7,7Ј-bis(4,4Ј-di-O-tert-
butyldimethylsilyloxyphenyl)butane-7,7Ј-dione (29) (7.37 g, 14
mmol, 22.4%) as a colourless oil, δH(300 MHz; CDCl3; Me4Si)
0.23 (12 H, s, 4Me-TBS), 0.98 (18 H, s, 6Me-TBS), 1.27 (6 H, d,
J 6.9, 9-3H, 9Ј-3H), 3.90 (2 H, m, 8-H, 8Ј-H), 6.86 (4 H, d, J 8.7,
3-H, 5-H, 3Ј-H, 5Ј-H), 7.91 (4 H, d, J 8.7, 2-H, 6-H, 2Ј-H,
6Ј-H); δC(300 MHz; CDCl3; Me4Si) Ϫ4.2, 15.8, 18.3, 25.6, 43.2,
119.8, 129.5, 130.6, 159.9 and 202.8, and meso-(8R,8ЈS)-8,8Ј-
dimethyl-7,7Ј-bis(4,4Ј-di-O-tert-butyldimethylsilyloxyphenyl)-
butane-7,7Ј-dione (28) (3.47 g, 6.6 mmol, 10.6%) as a colourless
oil, δH(300 MHz; CDCl3; Me4Si) 0.25 (12 H, s, 4Me-TBS), 1.0
(18 H, s, 6Me-TBS), 1.10 (6 H, d, J 6.3, 9-3H, 9Ј-3H), 3.97 (2 H,
m, 8-H, 8Ј-H), 6.90 (4 H, d, J 8.7, 3-H, 5-H, 3Ј-H, 5Ј-H), 7.99
(4 H, d, J 8.7, 2-H, 6-H, 2Ј-H, 6Ј-H); δC(300 MHz; CDCl3;
Me4Si) Ϫ4.2, 17.7, 18.3, 25.6, 43.0, 119.9, 130.3, 130.6, 160.4,
202.4.
To a solution of ( )-larreatricin-di-O-tert-butyldimethylsilyl
ethers (168 mg, 0.33 mmol) in dry THF (10 cm3) under N2 at
0 ЊC was added tetrabutylammonium fluoride (1.0 M in THF,
714 mm3, 0.71 mmol).29 Following stirring for 1 h, the reaction
mixture was quenched with saturated NH4Cl solution (25 cm3)
and extracted with EtOAc (2 × 50 cm3), with the resulting
organic solubles washed successively with water (25 cm3) and
brine solution (25 cm3). The organic solubles were next dried
(Na2SO4) and evaporated to dryness in vacuo, with the residue
reconstituted in a minimum amount of hexanes and subjected
to silica gel column chromatography (eluted with hexanes–
EtOAc, 3 : 2) to afford ( )-larreatricins (1) [(7R,7ЈR)-7,7Ј-
bis(4,4Ј-dihydroxyphenyl)-(8R,8ЈS)-8,8Ј-dimethyltetrahydro-
furan] (92 mg, 0.32 mmol, 98%) as colourless needles, mp 163–
164 ЊC [lit.,1 161–163 ЊC (from C6H6 ϩ Et2O)]. 1H and 13C NMR
(Table 1), UV, IR and mass spectra were identical to those
reported in the literature.1
meso-3,3Ј-Didemethoxynectandrin B-di-O-tert-butyldimeth-
ylsilyl ether (282 mg, 0.55 mmol) was deprotected and puri-
fied in a similar manner as above to give meso-3,3Ј-didemeth-
oxynectandrin B (6) [(7R,7ЈS)-7,7Ј-bis(4,4Ј-dihydroxyphenyl)-
(8R,8ЈS)-8,8Ј-dimethyltetrahydrofuran] (151.6 mg, 0.53 mmol,
96.4%) as a colourless oil; δH(300 MHz; Me2CO-d6; Me4Si) 0.99
(6 H, d, J 6.6 Hz, 9-3H, 9Ј-3H), 2.22 (2 H, m, 8-H, 8Ј-H), 4.37
(2 H, d, J 6.9, 7-H, 7Ј-H), 6.83 (4 H, d, J 8.4, 3-H, 5-H, 3Ј-H,
5Ј-H), 7.3 (4 H, d, J 8.4, 2-H, 6-H, 2Ј-H, 6Ј-H), 8.31 (2 H, br s,
OH); for 13C NMR spectral data see Table 1; UV, IR and
EI-MS data were identical to those of isolated 6.
( )-8Ј-epi-Larreatricins (3) and ( )-3,3Ј-didemethoxyverrucosins
(5). The ( )-diketones (29) (740 mg, 1.4 mmol) were converted
exactly as above into the di-O-tert-butyldimethylsilyl ether deriv-
atives of (3) (321 mg, 0.63 mmol, 45%) as a colourless oil, δH(300
MHz; CDCl3; Me4Si) 0.21 (12 H, s, 4Me-TBS), 1.02 (18 H, s,
6Me-TBS), 1.05 (6 H, d, J 6.0, 9-3H, 9Ј-3H), 1.81 (2 H, m, 8-H,
8Ј-H), 4.66 (2 H, d, J 9.0, 7-H, 7Ј-H), 6.85 (4 H, d, J 8.4, 3-H,
5-H, 3Ј-H, 5Ј-H), 7.29 (4 H, d, J 8.4, 2-H, 6-H, 2Ј-H, 6Ј-H);
δC(300 MHz; CDCl3; Me4Si) Ϫ4.57, Ϫ4.54, 13.5, 18.0, 25.5, 50.7,
87.9, 119.5, 127.1, 134.8 and 154.6, and the di-O-tert-butyl-
dimethylsilyl ethers of 5 (179 mg, 0.35 mmol, 25%) as a colourless
oil; δH(300 MHz; CDCl3; Me4Si) 0.18 (6 H, s, 2Me-TBS), 0.20
(6 H, s, 2Me-TBS), 0.61 (3 H, d, J 6.9, 9Ј-3H), 0.98 (9 H, s, 3Me-
TBS), 0.99 (9 H, s, 3Me-TBS), 1.01 (3 H, d, J 6.6, 9-3H), 1.75
(1 H, m, 8Ј-H), 2.21 (1 H, m, 8-H), 4.35 (1 H, d, J 9.3, 7-H), 5.11
(1 H, d, J 8.7, 7Ј-H), 6.82 (2 H, d, J 8.4, 3Ј-H, 5Ј-H), 6.85 (2 H, d,
J 8.4, 3-H, 5-H), 7.20 (2 H, d, J 8.4, 2Ј-H, 6Ј-H), 7.35 (2 H, d,
J 8.4, 2-H, 6-H); δC(300 MHz; CDCl3; Me4Si) Ϫ4.34, Ϫ4.32, 14.8,
15.2, 18.2, 25.7, 45.9, 48.3, 82.7, 87.2, 119.5, 119.8, 127.7, 127.9,
133.3, 133.8, 154.4 and 155.0. These derivatives were then indi-
vidually deprotected with tetrabutylammonium fluoride in THF
exactly as described above to afford ( )-8Ј-epi-larreatricins (3)
[(7S,7ЈS)-7,7Ј-bis(4,4Ј-dihydroxyphenyl)-(8S,8ЈS)-8,8Ј-dimethyl-
tetrahydrofuran] (176 mg, 0.62 mmol, 98%) as colorless needles,
( )-Larreatricins (1) and meso-3,3Ј-didemethoxynectandrin B
(6). The meso-diketone (28) (650 mg, 1.23 mmol) was dissolved
in dry diethyl ether (5 cm3) under N2 at 0 ЊC, and added to a
suspension of lithium aluminium hydride (LAH) (150 mg, 3.95
mmol) in diethyl ether (5 cm3). Following stirring for 2 h, excess
LAH was destroyed by addition of ethyl acetate (50 cm3) with
the resulting suspension washed with water (25 cm3). The com-
bined organic solubles were then washed with brine solution
(25 cm3), dried (Na2SO4) and evaporated to dryness in vacuo
(670 mg). The crude product was next dissolved in dry methyl-
ene chloride (20 cm3) under N2 at 0 ЊC, and added to a suspen-
sion of methanesulfonyl chloride (216 mm3, 2.79 mmol) in tri-
ethylamine (885 mm3, 6.35 mmol) with the contents being
stirred for 1 h. The reaction mixture was quenched with satur-
ated NH4Cl solution (30 cm3) and extracted with ethyl acetate
(2 × 50 cm3). The organic solubles were then washed succes-
sively with water (30 cm3) and brine solution (30 cm3), dried
(Na2SO4) and evaporated to dryness in vacuo. The residue so
obtained was reconstituted in a minimum amount of hexanes
and subjected to silica gel column chromatography (eluted with
hexanes–EtOAc, 95 : 5) to afford the di-O-tert-butyldimethyl-
silyl ether derivative of 1 (168 mg, 0.33 mmol, 26.6%) as a
colourless oil, δH(300 MHz; CDCl3; Me4Si) 0.17 (12 H, s, 4Me-
TBS), 0.59 (3 H, d, J 6.9, 9Ј-3H), 0.97 (3 H, d, J 6.9, 9-3H), 0.97
(18 H, s, 6Me-TBS), 2.41 (2 H, m, 8-H, 8Ј-H), 4.63 (1 H, d,
J 9.3, 7-H), 5.44 (1 H, d, J 4.2, 7Ј-H), 6.80 (2 H, d, J 8.4, 3Ј-H,
5Ј-H), 6.82 (2 H, d, J 8.4, 3-H, 5-H), 7.18 (2 H, d, J 8.4, 2Ј-H,
6Ј-H), 7.24 (2 H, d, J 8.4, 2-H, 6-H); δC(300 MHz; CDCl3;
Me4Si) Ϫ4.35, Ϫ4.33, 9.5, 11.8, 18.2, 18.3, 25.7, 43.3, 47.6, 84.7,
85.4, 119.5, 119.8, 127.0, 127.1, 133.2, 135.7, 154.2 and 154.8,
and the di-O-tert-butyldimethylsilyl ether derivative of 6 (282
mg, 0.55 mmol, 44.7%) as a colourless oil, δH(300 MHz; CDCl3;
Me4Si) 0.19 (12 H, s, 4Me-TBS), 0.98 (18 H, s, 6Me-TBS), 1.0
(6 H, d, J 6.9, 9Ј-3H, 9-3H), 2.29 (2 H, m, 8-H, 8Ј-H), 4.44 (2 H,
d, J 6.6, 7-H, 7Ј-H), 6.82 (4 H, d, J 8.7, 3-H, 5-H, 3Ј-H, 5Ј-H),
7.29 (4 H, d, J 8.7, 2-H, 6-H, 2Ј-H, 6Ј-H); δC(300 MHz; CDCl3;
Me4Si) Ϫ4.31, Ϫ4.29, 12.9, 18.2, 25.7, 44.6, 87.2, 119.8, 127.4,
134.7 and 154.9.
1
mp 232–234 ЊC [lit.,1 230–232 ЊC (from Me2CO)], H and 13C
NMR (Table 1), UV, IR and mass spectra were identical to those
reported in the literature;1 and ( )-3,3Ј-didemethoxyverrucosins
(5)
[(7S,7ЈR)-7,7Ј-bis(4,4Ј-dihydroxyphenyl)-(8S,8ЈS)-8,8Ј-di-
methyltetrahydrofuran] (97 mg, 0.34 mmol, 97%) as a colourless
oil; δH(300 MHz; Me2CO-d6; Me4Si) 0.61 (3 H, d, J 7.0, 9Ј-3H),
1.00 (3 H, d, J 6.4, 9-3H), 1.67 (1 H, m, 8Ј-H), 2.21 (1 H, m, 8-H),
4.29 (1 H, d, J 9.0, 7-H), 5.06 (1 H, d, J 8.7, 7Ј-H), 6.82 (2 H, d,
J 8.4, 3Ј-H, 5Ј-H), 6.85 (2 H, d, J 8.4, 3-H, 5-H), 7.23 (2 H, d,
J 8.4, 2Ј-H, 6Ј-H), 7.35 (2 H, d, J 8.4, 2-H, 6-H); for 13C NMR
spectral data see Table 1; UV, IR and EI-MS data were identical
to those of isolated 5.
Chiral HPLC Analyses
Synthetic ( )-larreatricins (1), ( )-8Ј-epi-larreatricins (3),
( )-3,3Ј-didemethoxyverrucosins (5) and meso-3,3Ј-didemeth-
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 3 0 7 – 2 3 1 3
2312