4
998 J . Org. Chem., Vol. 64, No. 13, 1999
Notes
(
s, 1H), 7.89 (s, 1H), 8.20 (d, J ) 8.8 Hz, 2H), 8.26 (d, J ) 8.8
dissolved in methanol (2 mL) and stirred a further 30 min. The
solvent was again removed and the residue partitioned between
dichloromethane (15 mL) and saturated NaHCO solution (1
3
1
3
Hz, 2H); C NMR (75 MHz, CDCl
8.3 (C), 20.3 (CH ), 25.9 (CH
CH ), 67.2 (CH), 67.4 (CH), 73.5 (CH), 82.2 (CH), 108.6 (C),
3
) δ -4.6 (CH
3
),. -4.5 (CH
3
),
1
(
3
), 25.8 (3 × CH
3
3
), 28.3 (CH
3
), 32.9
2
mL). The organic layer was separated, the aqueous layer was
1
1
1
23.4 (2 × CH), 130.9 (2 × CH), 135.6 (C), 137.0 (C), 138.3 (CH),
50.5 (C), 151.5 (CH), 163.8 (C). Potassium carbonate (24 mg,
67 mmol) was added to a solution of the ester (58.4 mg, 111
extracted with dichloromethane (3 × 15 mL), and the organic
2 4
layers were combined, dried (Na SO ), and evaporated in vacuo.
Flash chromatography (silica, 2:3 ethyl acetate/hexane) gave the
bis(oxazole) 9a ,b (30.5 mg, 40%) as a colorless gum as a 1:1
mixture of epimers at C10 (bengazole numbering): IR (NaCl,
mmol) in methanol (6 mL) and dichloromethane (0.6 mL). After
being stirred for 16 h, the solution was diluted with ethyl acetate
-
1
1
(
50 mL) and washed with water (30 mL) and brine (30 mL). The
aqueous layers were combined and extracted with ethyl acetate
40 mL), and the organic layers were combined, dried, and
neat) ν 3205, 1103, 1068 cm
3
; H NMR (300 MHz, CDCl ) δ
-0.03 (s, 3H), 0.06 (s, 3H), 0.07 (s, 6H), 0.86 (s, 9H), 0.87 (s,
9H), 1.05 (d, 3H, J ) 6.0 Hz), 1.27 (s, 3H), 1.44 (s, 3H), 1.93-
2.01 (m, 2H), 3.77-3.87 (m, 3H), 4.93 (dd, 1H, J ) 9.1, 4.5 Hz),
5.98 (s, 0.5H), 6.00 (s, 0.5H), 7.08 (s, 0.5H), 7.07 (s, 0.5H), 7.56
(
evaporated in vacuo. Flash chromatography (silica, 2:3 ethyl
acetate/hexane) gave alcohol 5a (39.2 mg, 96%, 67% from 5b)
as an orange oil (>85% ds) that was repurified by HPLC as
described above (5a , ds >95%).
(bs, 1H), 7.86 (s, 1H); 13C NMR (75 MHz, CDCl
-4.8 (CH ), -4.6 (CH ), -4.5 (CH
25.8 (3 × CH ), 25.8 (CH ), 25.9 (3 × CH
(CH ), 62.1 (CH), 65.3 (CH), 67.3 (CH), 73.5 (CH), 82.1 (CH),
108.2 (C), 124.8 (CH), 136.3 (CH), 143.5, 143.6 (C), 149.4 (C),
151.5 (CH), 161.3, 161.6 (C); HRCIMS (NH ) found m/z 583.3243
) δ -4.8 (CH
),
),
3
3
3
3
3
3
), 18.1 (C), 18.3 (C), 20.2 (CH
), 28.4 (CH
Red u ction of Keton e 6 (Meth od A). Sodium borohydride
3
3
3
3
), 37.8
(
9.4 mg, 0.25 mmol) was added to ketone 6 (18.3 mg, 50 µmol)
2
in 2,2,2-trifluoroethanol (2 mL) at -45 °C. The solution was al-
lowed to warm to -20 °C, and after it was stirred at -20 °C for
3
+
2
0 min, saturated NaHCO
3
solution (0.2 mL) was added. After
51 2 7 2
(MH ), C28H N O Si requires 583.3235.
the solution was stirred for 5 min, the solvent was evaporated
Myr ista te Ester 10a ,b. Myristic acid (7.9 mg, 34.6 µmol),
oxalyl chloride (0.1 mL), N,N-dimethylformamide (20 µL), and
dichloromethane (0.5 mL) were stirred at ambient temperature
for 2 h and then evaporated in vacuo. Dichloromethane (1 mL)
was added and evaporated in vacuo, and this step was repeated.
The myristoyl chloride was dissolved in dichloromethane (0.2
mL) and triethylamine (0.1 mL), and alcohol 9a ,b (15.5 mg, 26.6
µmol) in dichloromethane (0.5 mL) was added. The volume was
reduced with a stream of nitrogen to ca. 0.2 mL, 4-(dimethyl-
amino)pyridine (1 mg) added, and the solution stirred at ambient
and the residue triturated with dichloromethane (6 × 50 mL).
2 4
The combined extracts were dried (Na SO ) and evaporated in
vacuo to give the epimeric alcohols 5a :5b (17.2 mg, 94%) in a
ratio of ca. 10:3.
Red u ction of Keton e 6 (Meth od B). Sodium borohydride
(
1.9 mg, 56 µmol) was added to ketone 6 (2.1 mg, 5.6 µmol) in
methanol (0.5 mL) at 0 °C. After the solution was stirred at 0
C for 20 min, saturated NaHCO solution (0.1 mL) was added.
°
3
After the solution was stirred for 5 min, the solvent was evap-
orated and the residue triturated with dichloromethane (6 × 10
3
temperature for 21 h. Saturated NaHCO solution (1 mL) was
mL). The combined extracts were dried (Na
2
SO
4
) and evaporated
added and the biphasic mixture stirred rapidly for 30 min. Di-
chloromethane (5 mL) and water (2 mL) were added, the organic
layer was separated, and the aqueous layer was extracted with
dichloromethane (5 mL). The organic layers were combined,
in vacuo to give the epimeric alcohols (1.9 mg, 90%) in a ratio of
ca. 5:2 5a :5b.
2
7
Silyl Eth er 7. 2,6-Lutidine (42 µL, 0.34 mmol) was added
to alcohol 5a (50.0 mg, 0.135 mmol) in dichloromethane (0.5 mL).
tert-Butyldimethylsilyl trifluoromethanesulfonate (50 µL, 0.20
mmol) was added and the mixture stirred at ambient temper-
dried (Na
(silica, 1:9 ethyl acetate/hexane) gave ester 10a ,b (17.7 mg, 84%)
as a colorless oil: 1H NMR (300 MHz, CDCl
) δ -0.11 (s, 3H),
2 4
SO ), and evaporated in vacuo. Flash chromatography
3
ature for 1 h. Dichloromethane (10 mL) and saturated NaHCO
solution (0.1 mL) were added, and the mixture was stirred for 2
min, dried (Na SO ), and evaporated in vacuo. Flash chroma-
tography (silica, 1:9 ethyl acetate/hexane) gave silyl ether 7 (64.5
mg, 99%) as a colorless oil: IR (NaCl, neat) ν 1514, 1096, 1061,
3
0.06 (s, 9H), 0.79-0.94 (m, 3H), 0.87 (s, 18H), 1.17-1.38 (m,
15H), 1.42 (d, J ) 2.4 Hz, 3H), 1.58-1.67 (m, 2H), 1.96-2.00
(m, 2H), 2.31-2.43 (m, 2H), 3.77-3.90 (m, 3H), 4.91 (t, J ) 5.4
Hz, 1H), 7.04 (s, 1H), 7.20 (bs, 1H), 7.57 (s, 1H), 7.88 (s, 1H).
Ben ga zole A (1) a n d 10-epi-Ben ga zole A (1a ). Ester 10a ,b
(17.7 mg, 22.3 µmol) was dissolved in a mixture of 40% aqueous
hydrofluoric acid (0.3 mL) and acetonitrile (0.7 mL) and then
stirred at ambient temperature for 90 min. Chloroform (10 mL)
2
4
-
1 1
1
6
3
3
006 cm ; H NMR (300 MHz, CDCl ) δ -0.03 (s, 3H), 0.06 (s,
H), 0.07 (s, 3H), 0.86 (s, 18H), 1.04 (d, 3H, J ) 6.0 Hz), 1.27 (s,
H), 1.44 (s, 3H), 1.93-2.01 (m, 2H), 3.76-3.86 (m, 3H), 4.94
dd, 1H, J ) 9.0, 4.5 Hz), 7.57 (s, 1H), 7.84 (s, 1H); C NMR (75
1
3
(
3
and 50% saturated NaHCO solution (2 mL) were added, the
organic layer separated, and the aqueous layer extracted with
MHz, CDCl
8.2 (CH ), 18.3 (CH
CH ), 28.5 (CH ), 38.1 (CH
2.2 (CH), 108.2 (C), 135.5 (CH), 143.1 (C), 151.0 (CH); HRCIMS
3
) δ -4.8 (CH
), 20.3 (CH
), 65.4 (CH), 67.3 (CH), 73.7 (CH),
3
), -4.7 (CH
3
), -4.6 (CH
3
), -4.5 (CH
3
),
1
(
8
3
3
3
), 25.8 (CH
3
), 25.9 (CH
3
), 26.0
chloroform (3 × 10 mL). The organic extracts were combined,
3
3
2
2 4
dried (Na SO ), and evaporated in vacuo to leave 1 (bengazole
A) and 1a as a yellow oil (11.1 mg, 94%). HPLC of 1/1a gave a
single peak (C18 3 µm Microsorb 4.8 × 100 mm, 9:1 MeOH/H O,
rt 5.5 min) identical with that of natural 1. UV identical with 1.
+
(NH
3
) found m/z 486.3065 (MH ), C24
Oxa zole-5-ca r boxa ld eh yd e (8). Amberlyst-15 (0.48 g) was
H
48NO
5
Si
2
requires 486.3071.
2
2
8
1
13
added to a vigorously stirring solution of oxazole-5-carboxalde-
hyde diethyl acetal2 (0.50 g, 2.9 mmol) and water (0.17 mL, 9.5
mmol) in acetone (12 mL). After 1 h, the resin was removed by
filtration and washed with acetone (20 mL), and the filtrate and
washing were evaporated in vacuo. Flash chromatography
H NMR (600 MHz, CD
3 3
OD) and C NMR (150 MHz, CD OD)
1
data for the mixture of 1 and 1a were identical to those of the
1
b
natural product, with the exception of signal doubling for C6
1
3
1
( C NMR, δ 66.21, d, 66.18, d) and the following H NMR signals
(assigned for 1/1a , respectively): δ 2.43 (t, 2H) J ) 7.5 Hz/2.25
(
silica, 1:1 diethyl ether/pentane) gave aldehyde 8 (0.19 g, 69%)
(t, 2H) J ) 7.5 Hz (R-myristate CH ); 1.14 (d, 3H, J ) 6.6 Hz)/
2
1
+
as colorless crystals: mp 29-33 °C (sublimes); H NMR (300
MHz, CDCl
) δ 7.88 (s, 1H), 8.11 (s, 1H), 9.85 (s, 1H); 13C NMR
75 MHz, CDCl ) δ 136.0 (CH), 148.2 (C), 154.3 (CH), 176.8 (C).
Bor a n e-Med ia ted Ad d ition of 2-Lith ioxa zole Bis(ox-
a zole) 9a ,b. BH ‚THF (140 µL, 140 µmol, 1.0 M in THF) was
3
1.13 (d, 3H, J ) 6.6 Hz) (CH ); ESIMS m/z 525 (MH , 100), 312
3
(63).
(
3
Ack n ow led gm en t. We are grateful to Scott Stanley
Equine Analytical Chemistry Laboratory, UC Davis)
1
4
(
3
for ESI MS spectra of 1/1a and Gillian Nicholas for
assistance with antifungal assays. Financial support for
this work was provided by the National Institutes of
Health (AI 39887). The Bruker DRX 600 MHz NMR
spectrometer was partially funded through NIH RR
added dropwise to silyl ether 7 (64.5 mg, 133 µmol) in THF (1
mL) at ambient temperature. After 30 min, the solution was
cooled to -78 °C and tert-butyllithium (161 µL, 273 µmol, 1.7 M
in pentane) added dropwise. After a further 30 min, aldehyde 8
(54 mg, 546 µmol) in THF (0.5 mL) was added dropwise. After
a further 4 h, methanol (2 mL) was added, and the solution was
allowed to warm to ambient temperature and stirred for 1 h.
The solvent was evaporated in vacuo, and the residue was
1
1973.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra for compounds 6, 7, 9a ,b, 10a ,b, and synthetic 1/1a .
This material is available free of charge via the Internet at
http://pubs.acs.org.
(
27) Corey, E. J .; Cho, H.; R u¨ cker, C.; Hua, D. H. Tetrahedron Lett.
981, 22, 3455-3458.
28) Coppola, G. M. Synthesis 1984, 1021-1023.
1
(
J O9906328