Ono et al.
CH2Cl2. The combined organic layer was washed with aqueous
1 M Na2SO3, H2O, and brine, dried over MgSO4, and concen-
trated in vacuo. Purification by silica gel column chromatog-
raphy (hexane/AcOEt ) 1:1) afforded 178 mg of 24 as an
amorphous solid (88%). 1H NMR (400 MHz, CDCl3) major
isomer: δ 0.29 (s, 3H), 0.88 (d, J ) 6.4 Hz, 3H), 1.20 (s, 6H),
2.42 (br d, J ) 13.2 Hz, 1H), 3.04-3.27 (m, 2H), 3.356 (s, 3H),
4.69 (s, 2H), 5.00 (br dd, J ) 6.6, 14.2 Hz, 1H), 7.44-7.49 (m,
6H), 7.68-7.78 (m, 4H); minor isomer: δ 0.83 (d, J ) 6.8 Hz,
3H), 1.21 (s, 6H), 3.362 (s, 3H), 4.70 (s, 2H), 5.26 (m, 1H). 13C
NMR (100 MHz, CDCl3): δ 11.8, 14.9, 18.9, 20.7, 22.3, 23.2,
26.4, 26.5, 27.7, 36.1, 36.5, 40.4, 42.3, 49.7, 55.1, 56.5, 63.4,
76.4, 81.6, 90.9, 128.3, 128.4, 130.7, 130.8, 131.0, 131.1, 131.4,
131.5, 144.5. EIMS: 536 (M+). HREIMS: calcd for C34H49O3P
(M+) 536.3420, found 536.3409.
11.3 Hz, 1H, 7-H), 5.93 (dddd, J ) 7.3, 7.3, 10.2, 17.0 Hz, 1H,
-CH2CHdCH2), 6.26 (d, J ) 11.3 Hz, 1H, 6-H). 13C NMR (150
MHz, CDCl3): δ 12.0, 18.8, 20.8, 22.3, 23.5, 27.7, 29.0, 29.2,
29.4, 33.2, 36.1, 36.4, 37.7, 40.4, 44.0, 44.4, 45.8, 49.2, 56.3,
56.5, 68.8, 71.0, 71.1, 115.3, 116.5, 123.5, 131.1, 137.6, 143.1.
IR (neat): 3420, 2928, 2868, 1640 cm-1. EIMS: 444 (M+).
HREIMS: calcd for C29H48O3 (M+) 444.3603, found 444.3609.
(a R,1R,3R,7E)-2-P r op yl-9,10-seco-19-n or ch olest a -5,7-
d ien e-1,3,25-tr iol (7a ) a n d (a S,1R,3R,7E)-2-P r op yl-9,10-
seco-19-n or ch olesta -5,7-d ien e-1,3,25-tr iol (7b). These ana-
logues were obtained through the same procedure as described
above for the synthesis of 6a and 6b. A crude product, which
was obtained from 23 (74 mg, 139 µmol), 13 (43 mg, 107 µmol),
and LiHMDS (1 M solution in THF, 130 µL, 130 µmol), was
partially purified by silica gel column chromatography (hexane/
AcOEt ) 40:1) to give protected 19-norvitamin D3 (51 mg,
66%). To a solution of the crude 19-norvitamin D3 (46 mg, 64
µmol) in dry MeOH (2 mL) was added (+)-CSA (45 mg, 194
µmol) at 0 °C, and the mixture was stirred at rt for 22 h. The
usual workup and purification on silica gel column chroma-
tography (hexane/AcOEt ) 3:2) afforded 22.0 mg of 7 as a
mixture of isomers in a ratio of ca. 1:1 (51%). The isomers were
separated by reversed-phase HPLC (YMC-Pack ODS column,
20 × 150 mm, 9.9 mL/min) using CH3CN/H2O (90:10) as a
solvent system. Data for 7a (2R-propylated 5): tR ) 14.2 min.
[R]21D: +21.3 (c 0.36, CHCl3). UV (EtOH) λmax: 243.5, 252.0,
(aS,1R,3R,7E)-2-Allyl-9,10-seco-19-n or ch olesta-5,7-dien e-
1,3,25-t r iol (6a ) a n d (a R,1R,3R,7E)-2-Allyl-9,10-seco-19-
n or ch olesta -5,7-d ien e-1,3,25-tr iol (6b). To a solution of 23
(31.1 mg, 58.3 µmol) in dry THF (200 µL) was added LiHMDS
(1 M solution in THF, 55 µL, 55 µmol) at -78 °C. After the
mixture was stirred at the same temperature for 1 h, a solution
of 12 (17.1 mg, 42.9 µmol) in dry THF (200 µL) was added
dropwise to the mixture. After being stirred for 3 h, the
reaction mixture was poured into saturated aqueous NH4Cl
and extracted with Et2O. The combined organic layer was
washed with brine, dried over Na2SO4, and concentrated in
vacuo. The residue was purified by column chromatography
on silica gel (hexane/AcOEt ) 30:1) to yield crude protected
19-norvitamin D3 (18.0 mg, ca. 59%). To a solution of the crude
protected 19-norvitamin D3 (9 mg, 13 µmol) in dry MeOH (2
mL) was added (+)-CSA (10 mg, 23 µmol) at 0 °C. After being
stirred at rt for 19 h, the reaction mixture was diluted with
AcOEt. The resulting mixture was washed with saturated
aqueous NaHCO3 and brine, dried over Na2SO4, and concen-
trated. Purification by silica gel column chromatography
(hexane/AcOEt ) 3:2) afforded 4.0 mg of 6 as a mixture of
isomers in a ratio of ca. 1:1 (47%). The isomers were separated
by reversed-phase HPLC (YMC-Pack ODS column, 20 × 150
mm, 9.9 mL/min) using CH3CN/H2O (85:15) as a solvent
1
262.0 nm; λmin 247.5, 258.5 nm. H NMR (600 MHz, CDCl3):
δ 0.53 (s, 3H, 18-H3), 0.94 (d, J ) 6.6 Hz, 3H, 21-H3), 0.96 (t,
J ) 7.1 Hz, 3H, -CH2CH2CH3), 1.07 (m, 1H), 1.22 (s, 6H, 26-
H3 and 27-H3), 1.24-1.32 (m, 5H), 1.36-1.40 (m, 4H), 1.45-
1.56 (m, 7H), 1.60-1.68 (m, 4H), 1.89 (m, 1H), 1.99-2.01 (m,
2H), 2.12-2.17 (m, 2H), 2.60 (dd, J ) 4.5, 12.5 Hz, 1H, 4R-H),
2.80 (dd, J ) 4.7, 12.6 Hz, 1H, 9â-H), 2.84 (dd, J ) 4.7, 14.0
Hz, 1H, 10R-H), 3.64 (dt, J ) 4.5, 9.2 Hz, 1H, 3R-H), 4.09 (br
s, 1H, 1â-H), 5.82 (d, J ) 11.3 Hz, 1H, 7-H), 6.37 (d, J ) 11.3
Hz, 1H, 6-H). 13C NMR (150 MHz, CDCl3): δ 12.0, 14.4, 18.8,
20.4, 20.8, 22.2, 23.5, 27.6, 28.9, 29.2, 29.3, 29.4, 35.5, 36.1,
36.4, 40.5, 44.4, 45.2, 45.8, 48.9, 56.3, 56.5, 68.3, 71.1, 71.6,
115.2, 124.0, 131.3, 143.2. IR (neat): 3384, 2955, 2872, 1613
cm-1. EIMS: 446 (M+). HREIMS: calcd for C29H50O3 (M+)
446.3760, found 446.3763. Data for 7b (2â-propylated 5): tR
) 13.8 min. [R]21D: +15.2 (c 0.32, CHCl3). UV (EtOH): λmax
243.5, 252.0, 261.5 nm; λmin 247.0, 258.0 nm. 1H NMR (600
MHz, CDCl3): δ 0.55 (s, 3H, 18-H3), 0.94 (d, J ) 6.6 Hz, 3H,
21-H3), 0.95 (t, J ) 7.3 Hz, 3H, -CH2CH2CH3), 1.07 (m, 1H),
1.22 (s, 6H, 26-H3 and 27-H3), 1.24-1.33 (m, 5H), 1.37-1.53
(m, 11H), 1.66-1.67 (m, 3H), 1.88-1.91 (m, 2H), 1.99-2.02
(m, 2H), 2.35 (ddd, J ) 1.2, 3.8, 12.9 Hz, 1H, 4â-H), 2.40 (br d,
J ) 13.9 Hz, 1H, 4R-H), 2.80 (dd, J ) 4.7, 12.6 Hz, 1H, 9â-H),
3.10 (ddd, J ) 1.2, 4.4, 12.7 Hz, 1H, 10â-H), 3.54 (dt, J ) 4.4,
9.8 Hz, 1H, 1â-H), 4.05 (br s, 1H, 3R-H), 5.87 (d, J ) 11.3 Hz,
1H, 7-H), 6.26 (d, J ) 11.3 Hz, 1H, 6-H). 13C NMR (150 MHz,
CDCl3): δ 12.0, 14.4, 18.8, 20.2, 20.8, 22.3, 23.5, 27.7, 29.0,
29.2, 29.4, 29.6, 36.1, 36.4, 37.8, 40.5, 44.1, 44.4, 45.8, 49.1,
56.3, 56.5, 68.0, 71.1, 71.2, 115.3, 123.4, 131.3, 143.0. IR
(neat): 3382, 2942, 2872, 1613 cm-1. EIMS: 446 (M+). HRE-
IMS: calcd for C29H50O3 (M+) 446.3760, found 446.3757.
system. Data for 6a (2R-allylated 5): tR ) 16.6 min. [R]23
:
D
+22.3 (c 0.16, CHCl3). UV (EtOH): λmax 243.5, 252.0, 261.5
1
nm; λmin 247.5, 258.5 nm. H NMR (600 MHz, CDCl3): δ 0.53
(s, 3H, 18-H3), 0.94 (d, J ) 6.3 Hz, 3H, 21-H3), 1.06 (m, 1H),
1.22 (s, 6H, 26-H3 and 27-H3), 1.24-1.32 (m, 6H), 1.36-1.58
(m, 10H), 1.67 (m, 2H), 1.86-1.93 (m, 2H), 1.99-2.01 (m, 2H),
2.13-2.17 (m, 2H), 2.30 (ddd, J ) 6.0, 7.0, 14.2 Hz, 1H, -CH2-
CHdCH2), 2.50 (ddd, J ) 7.0, 8.4, 14.2 Hz, 1H, -CH2CHd
CH2), 2.61 (dd, J ) 4.7, 12.9 Hz, 1H, 4R-H), 2.80 (dd, J ) 4.4,
12.9 Hz, 1H, 9â-H), 2.86 (dd, J ) 4.1, 13.8 Hz, 1H, 10R-H),
3.70 (dt, J ) 4.7, 9.6 Hz, 1H, 3R-H), 4.08 (dt, J ) 4.1, 7.1 Hz,
1H, 1â-H), 5.07 (d, J ) 10.2 Hz, 1H, -CH2CHdCH2), 5.15 (d,
J ) 17.0 Hz, 1H, -CH2CHdCH2), 5.81 (d, J ) 11.3 Hz, 1H,
7-H), 5.92 (dddd, J ) 6.9, 6.9, 10.2, 17.0 Hz, 1H, -CH2CHd
CH2), 6.34 (d, J ) 11.3 Hz, 1H, 6-H). 13C NMR (150 MHz,
CDCl3): δ 12.0, 18.8, 20.8, 22.2, 23.4, 27.6, 28.9, 29.1, 29.3,
32.8, 35.5, 36.1, 36.4, 40.4, 44.4, 45.2, 45.8, 48.9, 56.3, 56.5,
68.7, 71.0, 71.2, 115.2, 116.5, 124.1, 131.2. IR (neat): 3353,
2936, 1644 cm-1. EIMS: 444 (M+). HREIMS: calcd for
29H48O3 (M+) 444.3603, found 444.3597. Data for 6b (2â-
(a R,1R,3R,7E)-2-(3-H yd r oxyp r op yl)-9,10-seco-19-n or -
ch olesta -5,7-d ien e-1,3,25-tr iol (8a ) a n d (a S,1R,3R,7E)-2-
(3-H yd r oxyp r op yl)-9,10-seco-19-n or ch olest a -5,7-d ien e-
1,3,25-tr iol (8b). These analogues were obtained through the
same procedure as described above for the synthesis of 6a and
6b. A crude product, which was obtained from 23 (28.8 mg,
54.0 µmol), 15 (21.8 mg, 41.1 µmol), and LiHMDS (1 M solution
in THF, 50 µL, 50 µmol), was partially purified by silica gel
column chromatography (hexane/AcOEt ) 30:1) to give pro-
tected 19-norvitamin D3 (30.5 mg). To a solution of the crude
19-norvitamin D3 (30.0 mg, 35.9 µmol) in dry MeOH (1 mL)
was added (+)-CSA (42 mg, 180 µmol) at 0 °C, and the mixture
was stirred at rt for 38 h. The usual workup and purification
on silica gel column chromatography (AcOEt/MeOH ) 10:1)
C
allylated 5): tR ) 16.0 min. [R]22D: +13.8 (c 0.13, CHCl3). UV
1
(EtOH): λmax 243.5, 252.0, 261.5 nm; λmin 247.0, 258.0 nm. H
NMR (600 MHz, CDCl3): δ 0.55 (s, 3H, 18-H3), 0.94 (d, J )
6.6 Hz, 3H, 21-H3), 1.07 (m, 1H), 1.22 (s, 6H, 26-H3 and 27-
H3), 1.24-1.33 (m, 5H), 1.37-1.57 (m, 11H), 1.66-1.70 (m,
2H), 1.88-1.92 (m, 2H), 1.99-2.02 (m, 2H), 2.28 (ddd, J ) 7.4,
7.7, 14.6 Hz, 1H, -CH2CHdCH2), 2.34 (ddd, J ) 1.4, 3.4, 14.0
Hz, 1H, 4â-H), 2.40 (br d, J ) 14.0 Hz, 1H,4R-H), 2.53 (ddd, J
) 6.7, 7.4, 14.6 Hz, 1H, -CH2CHdCH2), 2.80 (dd, J ) 4.2,
12.9 Hz, 1H, 9â-H), 3.11 (ddd, J ) 1.4, 4.7, 12.8 Hz, 1H, 10â-
H), 3.64 (dt, J ) 4.7, 10.3 Hz, 1H, 1â-H), 4.02 (ddd, J ) 3.4,
6.3, 6.9 Hz, 1H, 3R-H), 5.07 (d, J ) 10.2 Hz, 1H, -CH2CHd
CH2), 5.16 (d, J ) 17.0 Hz, 1H, -CH2CHdCH2), 5.87 (d, J )
7414 J . Org. Chem., Vol. 68, No. 19, 2003