Mayer et al.
3.27 (1H, q, J ) 6.5).11 13C NMR (90 MHz, CDCl
aqueous phase. After extraction of the aqueous layer with CH
Cl
(3 × 50 mL), the combined organic phase was dried and
evaporated. Kugelrohr distillation gave rac-cis-14 (2.75 g, 84%)
as a colorless liquid. GC-data: Column A [10 psi, H , 135 °C
iso), tR1 ) 3.2 min, tR2 ) 3.3 min]. R (petroleum ether/EtOAc,
:1) ) 0.83, (detection I); bp20mbar (Kugelrohr): 130-135 °C;
2
-
3
): δ ) -5.0,
-4.3, 14.1, 18.2, 22.7, 25.3, 25.9, 29.3, 29.7, 31.9, 34,8, 44.9,
2
+
3
Si): calcd 271.2093 [M - CH ] ;
56.0, 74.7. HRMS (C15
+
3
found 271.2093 [M - CH ] .
H
31
O
2
2
(
f
(3R,9R,10R)-Hep ta d ec-1-en e-4,6-d iyn e-3,9,10-tr iol, (3R,
9R,10R)-P a n a xytr iol, (3R,9R,10R)-1. To a stirred solution
of (R)-5 (0.11 g, 1.04 mmol) in dry THF (10 mL) was added
n-BuLi (0.85 mL of a 2.5 M solution in hexane, 2.08 mmol) at
-78 °C. After 30 min, HMPA (3 mL) and a solution of (2R,3R)-
16 (0.33 g, 1.14 mmol) in THF (5 mL) were added dropwise at
-78 °C, and the reaction was stirred for 3 h at 80 °C. The
reaction was quenched by addition of H O (30 mL) and Et O
2
1
H NMR (360.13 MHz, CDCl
3
): δ ) 0.89 (3H, s), 1.29-1.54
(
3
2
12H, m), 3.06 (1H, s), 3.21-3.25 (1H, m), 3.45-3.51 (1H, m),
1
3
.65-3.70 (1H, m). C NMR (90 MHz, CDCl
3
): δ ) 14.2, 22.8,
6.6, 27.6, 29.3, 29.5, 31.9, 41.7, 55.9, 58,2. HRMS (C10
19 1
H O -
+
+
Cl): calcd 191.1124 [M] ; found 190.1147 [M] and HRMS
(C H O ): calcd 155.1436 [M - Cl] ; found 155.1427 [M -
10 19 1
Cl]
+
2
2
+
.
(40 mL). The phases were separated, and the aqueous layer
was extracted with Et
O (2 × 30 mL). The combined organic
phases were dried and evaporated. The residue was dissolved
th r eo-1-Ch lor o-2,3-d eca n ed iol r a c-cis-15. Epoxide rac-
cis-14 (0.5 g, 2.6 mmol) was hydrolyzed in a mixture of water
2
+
-
(
2
5 mL) and THF (5 mL) under acidic conditions (6 N H
0 drops) without argon atmosphere. After 5 h the reaction
was complete. The solution was extracted twice with EtOAc
20 mL). The combined organic layers were dried and evapo-
rated. The residue was purified by flash chromatography
petroleum ether/EtOAc, 5:1) to afford rac-cis-15 (0.13 g, 87%).
GC-data: Column A [10 psi, H , 135 °C (iso), tR1 ) 22.2 min
2R,3S), tR2 ) 24.0 min (2S,3R)]. R (petroleum ether/EtOAc,
:1) ) 0.16, (detection I); H NMR (500.13 MHz, CDCl ): δ )
.88 (3H, t, J ) 6.6), 1.24-1.55 (12H, m), 3.60-3.68 (3H, m),
.12 (1H, q, J ) 7.1). 13C NMR (125 MHz, CDCl
): δ ) 13.3,
1.9, 24.8, 28.5, 28.7, 31.0, 33.0, 46.1, 70.8, 73.0. HRMS
2
SO
4
,
in THF (10 mL), and Bu
After 30 min, the reaction was quenched with water (10 mL)
and Et O (20 mL). The phases were separated, and the
aqueous layer was extracted with Et
4
N F (0.36 g, 1.14 mmol) was added.
2
(
2
O (2 × 20 mL). The
combined organic phases were dried and evaporated. The
residue was purified by flash chromatography (petroleum
ether/EtOAc, 10:1) to afford (3R,9R,10R)-1 (0.19 g, 68%).
(
2
2
D
0
(
f
[R] -19.5 (c 0.83, CHCl ). R (petroleum ether/EtOAc, 1:1) )
3
f
1
1
5
0
4
2
(
H]
3
0.35, (detection I); H NMR (500.13 MHz, CDCl ): δ ) 0.90
3
(3H, t, J ) 7.1), 1.27-1.54 (12H, m), 2.02 (2H, s), 2.38 (1H, s),
2.58-2.64 (2H, m), 3.56-3.65 (2H, m), 4.94 (1H, d, J ) 4.5),
5.27 (1H, d, J ) 10.2), 5.46 (1H, d, J ) 17.1), 5.96 (1H, ddd, J
3
+
13
C
10
+
H
20
O
2
Cl): calcd 207.1152 [M - H] ; found 207.1157 [M -
) 17.0, 10.1, 5.5). C NMR (90 MHz, CDCl ): δ ) 14.1, 22.6,
3
.
25.0, 25.5, 29.2, 29.5, 31.7, 33.6, 63.5, 66.5, 70.9, 72.1, 73.0,
74.7, 78.1, 117.2, 136.0. HRMS (C17H O ): calcd 260.1776
24 2
1
2
cis-1,2-Ep oxy-3-d eca n ol r a c-cis-4. Diol rac-cis-15 (0.11 g,
.53 mmol) was dissolved in dry THF (5 mL), and NaH (1
mmol) was added. After 30 min, water (10 mL) was added
carefully. The solution was extracted three times with Et
20 mL). The combined organic layers were dried and concen-
trated. The residue was purified by flash chromatography
petroleum ether/EtOAc, 8:1) to afford rac-cis-4 (0.079 g, 87%)
+
+
0
[M - H
2
2
O] ; found 260.1775 [M - H O] .
(3S,9R,10R)-Hep ta d ec-1-en e-4,6-d iyn e-3,9,10-tr iol, (3S,
9R,10R)-P a n a xytr iol, (3S,9R,10R)-2. According to the pro-
cedure described above for (3R,9R,10R)-1, alcohol (S)-5 (0.09
g, 0.85 mmol) in dry THF (10 mL) was treated with n-BuLi
(0.70 mL of a 2.5 M solution in hexane, 1.7 mmol), with HMPA
(2 mL) and a solution of (2R,3R)-16 (0.27 g, 0.94 mmol) in THF
2
O
(
(
as a colorless liquid. GC-data: Column A [10 psi, H
2
, 135 °C
+
-
(
(
(
(
iso), tR1 ) 4.2 min (2S,3S), tR2 ) 4.3 min (2R,3R)]. R
f
(4 mL), and finally with Bu
4
N F (0.30 g, 0.94 mmol) to afford
1
petroleum ether/EtOAc, 1:1) ) 0.74, (detection I); H NMR
(3S,9R,10R)-2 (0.14 g, 59%) after flash chromatography (pe-
2
0
360.13 MHz, CDCl
12H, m), 1.87 (1H, d, J ) 5.7), 2.71-2.74 (1H, m), 2.83 (1H,
3
): δ ) 0.89 (3H, t, J ) 6.6), 1.29-1.63
troleum ether/EtOAc, 10:1). [R]D +24.3 (c 1.10, CHCl
3
),
+25.3 (c 3.9,
(petroleum ether/EtOAc, 1:1) ) 0.38, (detection
I); H NMR (360.13 MHz, CDCl ): δ ) 0.89 (3H, t, J ) 6.9),
.20-1.50 (12H, m), 2.18 (3H, bs), 2.57-2.61 (2H, m), 3.72-
.78 (2H, m), 4.93 (1H, d, J ) 5.5), 5.27 (1H, d, J ) 10.1), 5.48
20
which is consistent with literature [R]
D
1
3
t, J ) 4.9), 2.99 (1H, q, J ) 4), 3.42-3.48 (1H, m). C NMR
90 MHz, CDCl ): δ ) 14.1, 22.7, 25.3, 29.2, 29.6, 31.8, 34.5,
19 2
5.2, 55.4, 71.7. HRMS (C10H O ): calcd 171.1385 [M - H] ;
12
CHCl
3
).
R
f
(
4
3
1
3
+
1
3
(
+
.
found 171.1381 [M - H]
2R,3R)-1,2-Ep oxy-3-d eca n ol (2R,3R)-4 via Biotr a n s-
for m ation . Lyophilized whole cells of Streptomyces sp. FCC008
7 g) were rehydrated in Tris buffer (350 mL, pH 8.0, 50 mM)
(
13
1H, d, J ) 16.5), 5.95 (1H, ddd, J ) 17.0, 10.0, 5.4). C NMR
90 MHz, CDCl ): δ ) 14.1, 22.6, 25.0, 25.5, 29.2, 29.5, 31.7,
3.6, 63.5, 66.5, 70.9, 72.1, 73.0, 74.7, 78.1, 117.2, 136.0. HRMS
(
3
(
3
for 1 h, and epoxide rac-cis-14 (0.85 g, 4.46 mmol) was added
in one portion. The reaction was monitored by GC on a chiral
stationary phase. After shaking the mixture at 30 °C for 156
h, the reaction was complete, and the product was continuously
extracted with CH Cl (400 mL) for 24 h. The organic phase
2 2
was dried and concentrated. The residue was purified by flash
+
(C
17
H
24
O
2
+): calcd. 260.1776 [M - H
2
O] ; found 260.1775
2
[M-H O] .
Gen er a l P r oced u r e for th e Scr een in g for Bioca ta lytic
Activity of r a c-cis-14. Epoxide rac-cis-14 (5 µL) was hydro-
lyzed using rehydrated lyophilized cells (50 mg) in Tris-buffer
(1 mL, 0.05 M, pH 8.0) by shaking the mixture at 30 °C with
chromatography (petroleum ether/EtOAc, 8:1) to give (2R,3R)-4
1
20 rpm. The reactions were monitored by TLC and GC. After
2
D
0
(
0
-
0.71 g, 92%, ee ) 95%) as a colorless liquid. [R] -5.2 (c
146 h, the cells were removed by centrifugation, and products
2
0
.67, CHCl
5.6 (c 1.8, CHCl
2R ,3R )-3-t er t -Bu t yld im e t h ylsilyloxy-1,2-e p oxyd e -
3
), which is consistent with literature data [R]
were extracted with EtOAc (2 × 1 mL). The combined organic
D
1
2
3
)
2 4
layers were dried (Na SO ) and analyzed.
(
Syn th eses of Non r a cem ic Refer en ce Ma ter ia l a n d
Deter m in a tion of Absolu te Con figu r a tion . The absolute
configuration of (R)-Falcarinol (R)-3 and (S)-Falcarinol (S)-3
was confirmed by comparison with known optical rotation
values.6
ca n e (2R,3R)-16. A solution of alcohol (2R,3R)-4 (0.68 g, 4.0
mmol), TBDMSCl (0.9 g, 5.9 mmol), and imidazole (0.4 g, 5.9
mmol) in CH
overnight and poured into a mixture of sat. NaHCO
Cl
were separated, and the aqueous layer was extracted with CH
Cl
The residue was purified by flash chromatography (petroleum
2 2
Cl (30 mL) was stirred at room temperature
3
and CH
2
-
-
2
. The mixture was stirred vigorously for 30 min, the layers
The absolute configuration of compound (2R,3R)-4 was
2
confirmed by comparison with a known optical rotation value.
Since conflicting values have been reported,1
1,12
the absolute
2
. The combined organic phases were dried and concentrated.
configuration of (2R,3R)-4 was elucidated by GC analysis on
a chiral stationary phase by coinjection with the independently
synthesized (2R,3R)-enantiomer following a known proce-
2
0
ether) to afford (2R,3R)-16 (1.01 g, 89%). [R] +5.9 (c 1.38,
D
CHCl
3
). R
H NMR (360.13 MHz, CDCl
.90 (3H, t, J ) 7.1), 0.92 (9H, s), 1.29-1.56 (12H, m), 2.56
1H, dd, J ) 4.9, 2.7), 2.79 (1H, t, J ) 4.9), 2.91-2.94 (1H, m),
f
(petroleum ether/EtOAc, 3:1) ) 0.89, (detection I);
1
27
3
): δ ) 0.07 (3H, s), 0.13 (3H, s),
dure.
0
(
(E)-2-Decen -1-ol 17. To a stirred solution of LiAlH
4
(4.5 g,
39.5 mmol) in dry THF (80 mL) was added a solution of alkyne
9
120 J . Org. Chem., Vol. 67, No. 26, 2002