Total synthesis of (2S,3S,5S,10S)-6,9-Epoxynonadec-18-ene-7,10-diol and formal total synthesis of (+)-trans-kumausyne from D-arabinose

Full text of DOI:10.1021/jo010830a

9046
J . Org. Chem. 2001, 66, 9046-9051
Ch a r t 1
Tota l Syn th esis of (2S,3S,5S,10S)-
6,9-Ep oxyn on a d ec-18-en e-7,10-d iol a n d
F or m a l Tota l Syn th esis of
(+)-tr a n s-Ku m a u syn e fr om D-Ar a bin ose
Rajendrakumar Reddy Gadikota,*
Christopher S. Callam,* and Todd L. Lowary*,1
Department of Chemistry, The Ohio State University,
Columbus, Ohio 43210
lowary.2@osu.edu
Received August 16, 2001
In tr od u ction
Dihydroxytetrahydrofurans 12 and 53 (Chart 1) are
marine natural products that have been isolated from
Notheia anomala, a brown alga found along the southern
Australian coast. Recently, Capon and co-workers have
shown that these compounds and related analogues
inhibit larval development in parasitic nematodes in
vitro.2 These natural products have attracted the atten-
tion of synthetic chemists, and a number of syntheses of
5 have been completed.4 In contrast, only two total
syntheses of 1 can be found in the literature. The first,
reported by Garc´ıa, Soler, and Mart´ın, involved conver-
sion of n-heptanal to 1, via a route that had as its key
step a Sharpless asymmetric dihydroxylation.5 More
recently, Yoda and co-workers disclosed the synthesis of
1 from L-galactono-1,4-lactone.6 We report here an ef-
ficient total synthesis of 1 and its C6, C10, and C6/C10
epimers (2-4) from the readily accessible methyl 2,3-
anhydro-5-O-benzyl-R-D-lyxofuranoside (7). As part of
these investigations, we have also completed a formal
total synthesis (+)-trans-kumausyne (6), a natural prod-
uct isolated from the alga Laurencia nipponica yamada,7
which has been the subject of a number of synthetic
investigations.8
Resu lts a n d Discu ssion
In designing a route to 1-4, we chose 7 as an
appropriate starting material. As outlined in Figure 1,
the synthesis of the targets requires three major trans-
formations: a regioselective hydride opening of the
epoxide at C3, the introduction of an alkyl group at C1,
and chain elongation at C5.
(1) To whom correspondence should be addressed.
(2) Capon, R. J .; Barrow, R. A.; Rochfort, S.; J obling, M.; Skene, C.;
Lacey, E.; Gill, J . H.; Friedl, T.; Wadsworth, D. Tetrahedron 1998, 54,
2227.
The preparation of 7 was achieved in good overall yield
from D-arabinose as previously described (Scheme 1).9
Our initial attempts to reductively open epoxide 7 via
reaction with DIBAL-H at -78 °C gave a mixture of 8
and 9 in a disappointing 1:2 ratio. A series of other
hydride reagents were explored (Table 1), and LAH
proved to be the most convenient, providing the product
arising from C3 attack with a high degree of regioselec-
tivity. Thus, reaction of 7 with LAH at reflux in THF
gave the 3-deoxy arabinofuranoside derivative 8 in 82%
yield together with a 6% yield of the 2-deoxy isomer, 9.
The hydroxyl group in 8 was then benzoylated to afford
10 in excellent yield. Trimethylsilyltriflate-catalyzed
C-allylation of 10 with allyltrimethylsilane at 0 °C
produced a 1.4:1 mixture of tetrahydrofurans 11 and 12
in 89% yield. Although the two diastereomers could be
readily separated by chromatography, improving the
(3) Warren, R. G.; Wells, R. J .; Blount, J . F. Aust. J . Chem. 1980,
33, 891.
(4) (a) Williams, D. R.; Harigaya, Y.; Moore, J . L.; D’sa, A. J . Am.
Chem. Soc. 1984, 106, 2641. (b) Hatakeyama, S.; Sakurai, K.; Saijo,
K.; Takano, S. Tetrahedron Lett. 1985, 26, 1333. (c) Gurjar, M. K.;
Mainkar, P. S. Heterocycles 1990, 31, 407. (d) Chikashita, H.; Naka-
mura, Y.; Uemura, H.; Itoh, K. Chem. Lett. 1993, 477. (e) Capon, R.
J .; Barrow, R. A.; Skene, C.; Rochfort, S. Tetrahedron Lett. 1997, 43,
7609. (f) Wang, Z.-M.; Shen, M. J . Org. Chem. 1998, 63, 1414. (g) Mori,
Y.; Sawada, T.; Furukawa, H. Tetrahedron Lett. 1999, 40, 731.
(5) Garc´ıa, C.; Soler, M. A.; Mart´ın, V. S. Tetrahedron Lett. 2000,
41, 4127.
(6) Yoda, H.; Maruyama, K.; Takabe, K. Tetrahedron: Asymmetry
2001, 12, 1403.
(7) Suzuki, T.; Koizumi, K.; Suzuki, M.; Kurosawa, E. Chem. Lett.
1983, 1643.
(8) (a) Brown, M. J .; Harrison, T.; Overman, L. E. J . Am. Chem.
Soc. 1991, 113, 5378. (b) Osumi, K.; Sugimura, H. Tetrahedron Lett.
1995, 36, 5789. (c) Lee, E.; Yoo, S.-K.; Cho, Y.-S.; Cheon, H.-S.; Chong,
Y. H. Tetrahedron Lett. 1997, 38, 7757. (d) Andrey, O.; Glanzmann,
C.; Landais, Y.; Parra-Rapado, L. Tetrahedron 1997, 53, 2835. (e)
Boukouvalas, J .; Fortier, G.; Radu, I.-I. J . Org. Chem. 1998, 63, 916.
(f) Ferna´ndez de la Pradilla, R.; Montero, C.; Priego, J .; Mart´ınez-Cruz,
L. A. J . Org. Chem. 1998, 63, 9612. (g) Mereyala, H. B.; Gadikota, R.
R. Tetrahedron: Asymmetry 2000, 11, 743. (h) Garc´ıa, C.; Mart´ın, T.;
Mat´ın, V. S. J . Org. Chem. 2001, 66, 1420.
(9) Martin, M. G.; Ganem, B.; Rasmussen, J . R. Carbohydr. Res.
1983, 123, 332.
10.1021/jo010830a CCC: $20.00 © 2001 American Chemical Society
Published on Web 11/22/2001

Notes
J . Org. Chem., Vol. 66, No. 26, 2001 9047
Sch em e 1a
F igu r e 1.
diastereoselectivity of this reaction was clearly desirable.
We postulated that the 11/12 ratio could be improved in
favor of 11 by substituting the benzoate ester in 10 with
either a benzyl or MOM ether. Both compounds were
prepared, but upon C-allylation, no improvement in
diastereomeric ratio relative to 10 was observed.
The stereochemistry of the newly generated stereo-
center in the allyl C-glycosides was confirmed as follows.
First, Zemple´n deacylation of 11 and 12 afforded alcohols
13 and 14, respectively. Oxidation of 13 with OsO4 and
N-methylmorpholine oxide (NMO) followed by cleavage
of the resulting vicinal diol with NaIO4 gave lactol 15 in
92% yield as a 3:2 mixture of isomers. The structure of
15 could be readily determined by NMR spectroscopy. In
1
the H NMR spectrum, two acetal hydrogens at 5.38 and
5.62 ppm were apparent; in the 13C NMR spectrum,
resonances arising from the acetal carbons were present
at 100.5 and 100.6 ppm. In contrast, dihydroxylation of
14, followed by diol cleavage, gave the aldehyde 16, not
the isomeric lactol. The formation of lactol 15 from 13
and hydroxy aldehyde 16 from 14 clearly establishes the
stereochemical relationship between the hydroxyl and
allyl groups in these C-glycosides.
The stereochemistry of 13 was further proven by its
conversion to the known lactone 19. Oxidation of 15 with
PCC gave lactone 17 in 97% yield. The benzyl group was
removed in quantitative yield providing 18, which was
subsequently protected as a tert-butyldiphenylsilyl ether
19 (91%). Characterization of 19 by 1H and 13C NMR
spectroscopy showed it to be identical to that previously
reported.8e The elaboration of 19 to (+)-trans-kumausyne
(6) has been reported earlier,8e and thus a formal
synthesis of 6 has been achieved.
After confirming the structure of 11 and 12, the
synthesis of 1-4 could be completed (Schemes 2 and 3).
To achieve the total synthesis of 1 (Scheme 2), compound
11 was first dihydroxylated with OsO4/NMO. The result-
ing diol was treated with NaIO4 to afford an aldehyde
that was immediately treated with propylidene tri-
phenylphosphorane. The olefin product, 20, was obtained
in an 87% overall yield from 11 as a 1:3 ratio of E and Z
isomers. Hydrogenation of 20 over palladium on carbon
resulted in both the reduction of the alkene and depro-
tection of the benzyl group to give alcohol 21 in 91% yield.
On the basis of a previous report,4f we predicted that the
C10 stereocenter could be stereoselectively introduced
with the S stereochemistry, through oxidation of the
hydroxyl group in 21 to the corresponding aldehyde and
then reaction with the appropriate Grignard reagent. To
that end, 21 was oxidized under Swern conditions and
then immediately treated with 1-nonenylmagnesium
bromide10 in ether at -20 °C. Unexpectedly, this reaction
sequence afforded in 75% yield an inseparable 4:1
a
Key: (a) ref 9; (b) LiAlH4, THF, reflux, 88%, 8/9 13.5:1; (c)
BzCl, pyr, 0 °C f rt, 97%; (d) CH2dCHCH2TMS, TMSOTf,
CH3CN, -20 °C, 89% 11/12 1.4:1; (e) NaOCH3, CH3OH, rt, quant;
(f) OsO4, NMO, acetone/water (5:1), rt, then NaIO4, SiO2, CH2Cl2,
H2O, rt, 92%; (g) OsO4, NMO, acetone/water (5:1), rt, then NaIO4,
SiO2, CH2Cl2, H2O, rt, 85%; (h) PCC, NaOAc, 4 Å molecular sieves,
CH2Cl2, 97%; (i) Pd/C, H2, CH3OH, rt, quant; (j) TBDPSCl,
imidazole, DMF, rt, 91%.
Ta ble 1. Regioselectivity of Ep oxid e Op en in g in 7 by
Hyd r id e Rea gen ts
reagent
conditions
time (h) yield (%) ratio (8/9)a
DIBAL-H
LAH
-78 °C to rt
5
12
10
10
10
86
88
81
1:2
13.5:1
15:1
no reaction
no reaction
reflux (THF)
L-Selectride -78 °C to rt
K-Selectride -78 °C to rt
NaBH4
rt
a
Ratio based upon isolated yields of 8 and 9.
mixture of alcohols 22, with the desired 10S isomer being
the minor component. However, the stereochemistry at

9048 J . Org. Chem., Vol. 66, No. 26, 2001
Notes
Sch em e 2a
Sch em e 3a
a
Key: (a) (i) OsO4, NMO, acetone/H2O (5:1), (ii) NaIO4, SiO2,
CH2Cl2, H2O, rt, (iii) Ph3PCHCH2CH3, THF, -20 °C, 83% (three
steps); (b) Pd/C, H2, CH3OH, 94%; (c) Swern oxidation, CH2Cl2,
-78 °C, then CH2dCH(CH2)6CH2MgBr, THF, -40 °C, 76%; (d)
NaOCH3, CH3OH rt, quant; (e) PPh3, DIAD, BzOH, toluene, 0 °C;
(f) NaOCH3, CH3OH rt, 79% (two steps from 26).
a
Key: (a) (i) OsO4, NMO, acetone/H2O (5:1), (ii) NaIO4, SiO2,
CH2Cl2, H2O, rt, (iii) Ph3PCHCH2CH3, THF, -20 °C, 87%, (three
steps); (b) Pd/C, H2, CH3OH, 91%; (c) Swern oxidation, CH2Cl2,
-78 °C, then CH2dCH(CH2)6CH2MgBr, THF, -40 °C, 75%; (d) (i)
PPh3, DIAD, BzOH, toluene, 0 °C, (ii) NaOCH3, CH3OH rt, 77%.
In conclusion, we have developed a concise route for
the total synthesis of the marine natural product 1 and
its C6, C10, and C6/C10 epimers (2-4). A formal synthesis
of (+)-trans-kumausyne (6) has also been completed. The
general strategy described in this paper, the formation
of a 2,3,5-trisubstituted tetrahydrofuran residue via a
regioselective hydride ring opening of the epoxide moiety
in 7, should also enable the synthesis of other natural
products containing this substructure, for example, ku-
mausallene,11 laurefucin,12 and Hagen’s gland lactones.13
C10 could be readily inverted through a Mitsunobu
reaction affording 23. After deprotection of the benzoyl
esters from 23, it was possible to separate 1 from its
isomer 3. The spectral data of synthesized 1 were
identical with those reported for the natural compound.2
With a route to 1 in place, we then synthesized 2 and
4 starting from C-glycoside 12 as outlined in Scheme 3.
Thus, compound 12 was transformed into alkene 24 and
then alcohol 25 using the same sequence of reactions used
for the conversion of 11 into 21. Oxidation of 25 followed
by reaction of the corresponding aldehyde with 1-non-
enylmagnesium bromide10 afforded, in 76% yield, a 3:1
mixture of alcohols 26 and 27, which could be separated
by chromatography. A portion of the major isomer (26)
was deprotected affording 4 in quantitative yield. The
remainder was subjected to a Mitsunobu reaction, which
provided dibenzoate 28 with the stereochemistry at C10
inverted. Treatment of 28 with sodium methoxide af-
forded 2 (79%, two steps).
Exp er im en ta l Section
Gen er a l Meth od s. Solvents were distilled from the appropri-
ate drying agents before use. Unless stated otherwise, all
reactions were carried out under a positive pressure of argon
and were monitored by TLC on silica gel 60 F254 (0.25 mm, E.
Merck). Spots were detected under UV light or by charring with
10% H2SO4 in ethanol. Solvents were evaporated under reduced
pressure and below 40 °C (bath). Organic solutions of crude
products were dried over anhydrous Na2SO4. Column chroma-
tography was performed on silica gel 60 (40-60 µM). The ratio
(11) Suzuki, T.; Koizumi, K.; Suzuki, M.; Kurosawa, E. Chem. Lett.
1983, 1639.
(12) Kikuchi, H.; Suzuki, T.; Kurosawa, E.; Suzuki, M. Bull. Chem.
Soc. J pn. 1991, 64, 1763.
(10) Derguini-Boumechal, F.; Lorne, R.; Linstrumelle, R. Tetra-
hedron Lett. 1977, 1181.
(13) Williams, H. J .; Wong, M.; Wharton, R. A.; Vinson, S. B. J .
Chem. Ecol. 1988, 14, 1727.

Notes
J . Org. Chem., Vol. 66, No. 26, 2001 9049
between silica gel and crude product ranged from 100 to 50:1
(w/w). Optical rotations were measured at 21 ( 2 °C. Melting
points are uncorrected. 1H NMR spectra were recorded at 500.12
MHz, and chemical shifts are referenced to either TMS (0.0,
CDCl3) or external dioxane (3.75, D2O). 13C NMR spectra were
recorded at 125.75 MHz, and 13C chemical shifts are referenced
to CDCl3 (77.00, CDCl3) or external dioxane (68.11, D2O).
Electrospray mass spectra were recorded on samples suspended
in THF or CH3OH.
138.6, 134.5, 133.5, 130.5, 130.0, 128.9, 128.8, 128.7, 128.1, 128.0,
117.8, 82.1, 77.1, 75.1, 73.7, 73.0, 36.5, 34.3; HRMS (ESI) calcd
for (M + Na+) C22H24O4 375.1566, found 375.1583.
12: Rf 0.51 (hexanes/EtOAc, 4:1); [R]D +13.8 (c 1.3, CHCl3);
1H NMR (500 MHz, CDCl3, δ) 8.02 (dd, 2 H, J ) 1.0, 8.1 Hz),
7.60 (dd, 1 H, J ) 7.3, 7.5 Hz), 7.47-7.31 (m, 7 H), 5.96-5.90
(m, 1 H), 5.31 (ddd, 1 H, J ) 3.1, 6.2, 6.7 Hz), 5.22 (dd, 1 H, J
) 1.5, 15.4 Hz), 5.17 (dd, 1 H, J ) 1.0, 10.3 Hz), 4.67 (d, 1 H, J
) 12.2 Hz), 4.63 (d, 1 H, J ) 12.2 Hz), 4.47-4.44 (m, 1 H), 4.33
(ddd, 1 H, J ) 2.8, 6.5, 9.3 Hz), 3.70 (dd, 1 H, J ) 6.4, 9.8 Hz),
3.58 (dd, 1 H, J ) 5.0, 9.8 Hz), 2.57 (ddd, 1 H, J ) 7.2, 7.8, 12.2
Hz), 2.45-2.42 (m, 2 H), 2.05 (dddd, 1 H, J ) 3.3, 4.9, 5.0, 14.1
Hz); 13C NMR (125.7 MHz, CDCl3, δ) 166.5, 138.6, 134.1, 133.5,
130.4, 130.0, 128.8, 128.7, 128.1, 128.0, 118.2, 83.4, 78.4, 77.2,
73.8, 72.9, 38.0, 34.6; HRMS (ESI) calcd for (M + Na+) C22H24O4
375.1566, found 375.1583.
Met h yl 5-O-Ben zyl-3-d eoxy-r-D-th r eo-p en t ofu r a n osid e
(8) a n d Meth yl 5-O-Ben zyl-2-d eoxy-r-D-th r eo-p en tofu r a -
n osid e (9). To a solution of 7 (5.0 g, 19.6 mmol) in THF (100
mL) at 0 °C was added LiAlH4 (1.87 g, 49.0 mmol). The solution
was heated at reflux for 12 h. EtOAc (10 mL) was added, and
the reaction mixture was stirred for 10 min followed by the
addition of water (5 mL). The solution was diluted with EtOAc
(200 mL), filtered through Celite, and concentrated. The com-
pound was purified by chromatography (hexanes/EtOAc, 4:1) to
yield 8 (4.15 g, 82%) and 9 (0.31 g, 6%) as a colorless oils.
8: Rf 0.34 (hexanes/EtOAc, 2:1); [R]D +15.0 (c 0.9, CHCl3);
1H NMR (500 MHz, CDCl3, δ) 7.41-7.34 (m, 5 H), 4.87 (s, 1 H),
4.73 (d, 1 H, J ) 11.9 Hz), 4.58 (d, 1 H, J ) 11.9 Hz), 4.38 (ddd,
1 H, J ) 2.0, 4.2, 9.8 Hz), 4.07-4.00 (m, 2 H), 3.77 (dd, 1 H, J
) 1.9, 10.3 Hz), 3.48 (dd, 1 H, J ) 1.9, 10.3 Hz), 3.38 (s, 3 H),
2.45 (dddd, 1 H, J ) 4.8, 4.9, 9.8, 9.9 Hz), 1.82 (dd, 1 H, J ) 2.5,
13.7 Hz); 13C NMR (125.7 MHz, CDCl3, δ) 137.4, 129.0, 128.5,
128.4, 110.4, 77.4, 74.5, 74.2, 71.5, 54.9, 34.2; HRMS (ESI) calcd
for (2M + Na+) C26H36O8 499.230238, found 499.23550.
9: yield 0.31 g, 6%; Rf 0.30 (hexanes/EtOAc, 5:1); [R]D +71.1
(c 1.3, CHCl3); 1H NMR (500 MHz, CDCl3, δ) 7.40-7.36 (m, 5
H), 5.20 (dd, 1 H, J ) 5.0, 5.4 Hz), 4.67-4.60 (m, 2 H), 4.57-
4.55 (m, 1 H), 4.17 (dd, 1 H, J ) 4.7, 5.9 Hz), 3.85 (d, 2 H, J )
4.8 Hz), 3.40 (s, 3 H), 2.82 (bs, 1 H), 2.23-2.14 (m, 2 H); 13C
NMR (125.7 MHz, CDCl3, δ) 137.9, 128.9, 128.3, 128.2, 104.7,
78.7, 74.2, 72.8, 69.1, 55.6, 43.1; HRMS (ESI) calcd for (2M +
Na+) C26H36O8 499.230238, found 499.23540.
Meth yl 2-O-Ben zoyl-5-O-ben zyl-3-d eoxy-r-D-th r eo-p en to-
fu r a n osid e (10). To a solution of 8 (2.60 g, 10.9 mmol) in
pyridine (10 mL) at 0 °C was added benzoyl chloride (1.7 mL,
14.1 mmol) dropwise. The reaction mixture was warmed to room
temperature and stirred for 30 min before being diluted with
CH2Cl2 (100 mL). The organic layer was washed successively
with 5% HCl, a saturated aqueous NaHCO3 solution, and water.
The organic layer was then dried, filtered, and concentrated, and
the compound was purified by chromatography (hexanes/EtOAc,
6:1) to yield 10 (3.61 g, 97%) as a colorless oil: Rf 0.41 (hexanes/
EtOAc, 5:1); [R]D +14.0 (c 2.2, CHCl3); 1H NMR (500 MHz,
CDCl3, δ) 8.02 (dd, 2 H, J ) 1.0, 8.1 Hz), 7.59 (dd, 1 H, J ) 7.3,
7.5 Hz), 7.46-7.30 (m, 7 H), 5.35 (dd, 1 H, J ) 1.5, 6.4 Hz), 5.17
(s, 1 H), 4.69 (d, 1 H, J ) 12.3 Hz), 4.63 (d, 1 H, 12.3 Hz), 4.54-
4.49 (m, 1 H), 3.71 (dd, 1 H, J ) 6.5, 10.1 Hz), 3.63 (dd, 1 H, J
) 6.5, 10.1 Hz), 3.46 (s, 3 H), 2.62 (dddd, 1 H, J ) 6.4, 6.5, 8.4,
12.3 Hz), 1.93 (dddd, 1 H, J ) 1.5, 5.0, 5.1, 14.2 Hz); 13C NMR
(125.7 MHz, CDCl3, δ) 166.1, 138.5, 133.6, 130.2, 130.0, 128.9,
129.8, 128.1, 128.0, 107.6, 78.3, 77.6, 73.8, 72.9, 55.1, 32.9;
HRMS (ESI) calcd for (M + Na+) C20H22O5 365.1359, found
365.1381.
2-Ally l-5-b e n z y lo x y m e t h y l-3-p h e n y lc a r b o n y lo x y -
(2S,3S,5S)-tetr a h yd r o-3-fu r a n ol (11) a n d 2-Allyl-5-ben zy-
loxym eth yl-3-p h en ylca r bon yloxy-(2R,3S,5S)-tetr a h yd r o-3-
fu r a n ol (12). To a solution of 10 (3.42 g, 10.0 mmol) and
allyltrimethylsilane (3.3 mL, 20.0 mmol) in acetonitrile (100 mL)
at -20 ° C was added TMSOTf (3.6 mL, 20.0 mmol). The reaction
mixture was stirred for 4 h at that temperature and then diluted
with CH2Cl2. The solution was washed with an aqueous satu-
rated NaHCO3 solution and water before it was dried and
concentrated. The compound was purified by chromatography
(hexanes/EtOAc, 8:1) to yield a 1.4:1 mixture of 11 and 12 (3.15
g, 89% combined yield) as a colorless oils.
11: Rf 0.62 (hexanes/EtOAc, 4:1); [R]D +10.0 (c 0.6, CHCl3);
1H NMR (500 MHz, CDCl3, δ) 8.05 (dd, 2 H, J ) 1.0, 8.1 Hz),
7.61 (dd, 1 H, J ) 7.3, 7.5 Hz), 7.47-7.29 (m, 7 H), 5.89-5.87
(m, 1 H), 5.55-5.53 (m, 1 H), 5.15-5.07 (m, 2 H), 4.65 (d, 1 H,
J ) 12.2 Hz), 4.62 (d, 1 H, J ) 12.2 Hz), 4.00 (dd, 1 H, J ) 2.3,
6.8 Hz), 3.98-3.87 (m, 1 H), 3.70 (dd, 1 H, J ) 6.3, 9.9 Hz), 3.59
(dd, 1 H, J ) 4.8, 9.9 Hz), 2.62-2.55 (m, 3 H), 1.98 (dddd, 1 H,
J ) 1.7, 5.8, 5.8, 7.5 Hz); 13C NMR (125.7 MHz, CDCl3, δ) 166.2,
2-Allyl-5-ben zyloxym eth yl-(2S,3S,5S)-tetr a h yd r o-3-fu r a -
n ol (13). To a solution of 11 (800 mg, 2.27 mmol) in CH3OH (10
mL) was added 1 M NaOCH3 in CH3OH (0.5 mL). After being
stirred for 1 h at room temperature, the reaction mixture was
neutralized with Amberlite IR-120 (H+) resin, filtered, and
concentrated. The compound was purified by chromatography
(hexanes/EtOAc, 6:1) to yield 13 (560 mg, 100%) as a colorless
1
oil: Rf 0.31 (hexanes/EtOAc, 3:1); [R]D +61.0 (c 1.0, CHCl3); H
NMR (500 MHz, CDCl3, δ) 7.40-7.33 (m, 5 H), 5.96-5.88 (m, 1
H), 5.22 (dd, 1 H, J ) 3.5, 17.1 Hz), 5.10 (dd, 1 H, J ) 2.0, 11.2
Hz), 4.71 (d, 1 H, J ) 12.2 Hz), 4.58 (d, 1 H, J ) 12.2 Hz), 4.27-
4.23 (m, 1 H), 4.04 (br. s, 1 H), 3.82-3.70 (m, 3 H), 3.45 (dd, 1
H, J ) 2.1, 10.3 Hz), 2.51-2.48 (m, 2 H), 2.36 (ddd, 1 H, J )
5.3, 10.2, 12.9 Hz), 1.97 (dd, 1 H, J ) 2.8, 13.8 Hz); 13C NMR
(125.7 MHz, CDCl3, δ) 137.6, 135.5, 128.9, 128.4, 128.2, 117.1,
84.3, 76.7, 74.0, 72.2, 71.9, 37.5, 34.1; HRMS (ESI) calcd for (M
+ Na+) C15H20O3 271.1304, found 271.1323.
2-Allyl-5-ben zyloxym eth yl-(2R,3S,5S)-tetr a h yd r o-3-fu r a -
n ol (14). Compound 14 was prepared from 12 (600 mg, 1.7 mmol)
as described for the synthesis of 13 from 11. Purification by
chromatography (hexanes/EtOAc, 6:1) yielded 14 (420 mg, 100%)
as a colorless oil: Rf 0.28 (hexanes/EtOAc, 3:1); [R]D +43.6 (c
1
1.1, CHCl3); H NMR (500 MHz, CDCl3, δ) 7.39-7.30 (m, 5 H),
5.89-5.81 (m, 1 H), 5.15-5.10 (m, 2 H), 4.96 (d, 1 H, J ) 12.2
Hz), 4.58 (d, 1 H, J ) 12.2 Hz), 4.33 (dd, 1 H, J ) 2.5, 12.0 Hz),
4.10-4.04 (m, 3 H), 3.71 (dd, 1 H, J ) 2.3, 10.2 Hz), 3.49 (dd, 1
H, J ) 2.7, 10.2 Hz), 2.40-2.35 (m, 1 H), 2.25-2.15 (m, 2 H),
1.88 (dd, 1 H, J ) 3.0, 13.8 Hz); 13C NMR (125.7 MHz, CDCl3,
δ) 137.6, 134.8, 128.9, 128.4, 128.3, 117.7, 87.6, 77.2, 75.1, 74.1,
73.0, 38.5, 36.4; HRMS (ESI) calcd for (M + Na+) C15H20O3
271.1304, found 271.1323.
5-Ben zyloxym et h yl-(2S,3a S,6a S)-p er h yd r ofu r o[3,2-b]-
fu r a n -2-ylm eth a n ol (15). To a solution of compound 13 (400
mg, 1.61 mmol) and N-methylmorpholine oxide (227 mg, 1.94
mmol) in acetone/water (5:1, 10 mL) at 0 °C was added OsO4 (4
mg, 0.10 mmol). The reaction mixture was stirred for 12 h at
room temperature and then concentrated. The resulting residue
was dissolved in CH2Cl2 (10 mL), and solid sodium sulfite was
added. The mixture was filtered through Celite, silica gel (100-
200 mesh, 10 g) was added to the filtrate, and the mixture was
cooled to 0 °C. Sodium metaperiodate (690 mg, 3.22 mmol) was
added in a solution of water (2 mL). The reaction mixture was
stirred at room temperature for 1 h followed by filtration through
Celite. The filtrate was dried and concentrated, and the com-
pound was purified by chromatography (hexanes/EtOAc, 2:1) to
yield 15 (371 mg, 92%, 3:2 mixture of isomers) as a colorless oil:
Rf 0.19 (hexanes/EtOAc, 4:1); 1H NMR (500 MHz, CDCl3, δ)
7.34-7.26 (m, 5 H), 5.62-5.59 (m, 0.6 H), 5.38 (dd, 0.4 H, J )
6.3 11.7 Hz), 4.79-4.76 (m, 0.6 H), 4.69-4.68 (m, 0.4 H), 4.63-
4.42 (m, 3 H), 4.19-4.11 (m, 1 H), 3.80 (d, 0.6 H, J ) 4.3 Hz),
3.67 (dd, 0.4 H, J ) 2.7, 10.3 Hz), 3.54-3.42 (m, 2 H), 2.35-
2.99 (m, 3 H), 1.79 (dddd, 1 H, J ) 2.2, 6.7, 8.4, 13.8 Hz); 13C
NMR (125.7 MHz, CDCl3, δ) 138.5, 137.8, 129.0, 128.8, 128.7,
128.3, 128.2, 128.1, 128.0, 100.6, 100.5, 85.5, 84.3, 84.2,
83.1, 80.2, 79.9, 73.7, 73.6, 73.1, 70.0, 41.7, 41.0, 37.2, 35.9;
HRMS (ESI) calcd for (M + Na+) C14H18O4 273.1097, found
273.1104.
2-[5-Ben zyloxym eth yl-3-h yd r oxy-(2R,3S,5S)-tetr a h yd r o-
2-fu r a n yl]a ceta ld eh yd e (16). Compound 16 was prepared from
14 (400 mg, 1.61 mmol) as described for the preparation of 15
from 13. The compound was purified by chromatography (hex-

9050 J . Org. Chem., Vol. 66, No. 26, 2001
Notes
anes/EtOAc, 2:1) to yield 16 (343 mg, 85%) as a colorless oil: Rf
0.39 (hexanes/EtOAc, 1:1); [R]D +5.4 (c 1.0, CHCl3); 1H NMR
(400 MHz, CDCl3, δ) 9.76 (dd, 1 H, J ) 1.8, 2.4 Hz), 7.36-7.28
(m, 5 H), 4.65 (d, 1 H, J ) 12.2 Hz), 4.58-4.48 (m, 2 H), 4.35-
4.28 (m, 1 H), 4.14-4.00 (m, 2 H), 3.67 (dd, 1 H, J ) 2.5, 5.0
Hz), 3.48 (dd, 1 H, J ) 2.5, 5.0 Hz), 2.54-2.48 (m, 2 H), 2.40-
2.34 (m 1 H), 1.92-1.86 (m, 1 H); 13C NMR (100 MHz, CDCl3,
δ) 201.0, 137.5, 129.0, 128.7, 128.5, 128.1, 128.0, 82.7, 77.5, 75.8,
74.1, 72.6, 48.0, 36.2; HRMS (ESI) calcd for (M + Na+) C14H18O4
273.1097, found 273.1083.
(3a S,5S,6a S)-5-Ben zyloxym et h ylp er h yd r ofu r o[3,2-b]-
fu r a n -2-on e (17). To a stirred solution containing pyridinium
chlorochromate (452 mg, 2.09 mmol), powdered 4 Å molecular
sieves (100 mg), and sodium acetate (114 mg, 1.40 mmol) in CH2-
Cl2 (10 mL) was added a solution of 15 (350 mg, 1.40 mmol) in
CH2Cl2 (10 mL). The reaction mixture was stirred at room
temperature for 2 h, and then hexanes (5 mL) and diethyl ether
(5 mL) were added. The mixture was filtered through silica gel
and washed with excess diethyl ether. The resulting organic
solution was concentrated, and the compound was purified by
chromatography (hexanes/EtOAc, 2:1) to yield 17 (341 mg, 97%)
as a colorless oil: Rf 0.27 (hexanes/EtOAc, 4:1); [R]D +4.3 (c 0.5,
CHCl3); 1H NMR (400 MHz, CDCl3, δ) 7.36-7.26 (m, 5 H), 5.01
(dddd, 1 H, J ) 1.7, 4.3, 4.4, 6.4 Hz), 4.61-4.58 (m, 2 H), 4.53
(d, 1 H, J ) 12.2 Hz), 4.26-4.20 (m, 1 H), 3.54-3.47 (m, 2 H),
2.78-2.67 (m, 2 H), 2.39 (dddd, 1 H, J ) 6.8, 7.8, 7.9, 14.2 Hz),
2.03 (dddd, 1 H, J ) 1.7, 6.9, 7.0, 14.2 Hz); 13C NMR (100 MHz,
CDCl3, δ) 175.8, 138.3, 128.8, 128.6, 128.4, 128.2, 128.1, 84.5,
79.6, 79.5, 73.8, 72.7, 36.9, 35.0; HRMS (ESI) calcd for (M +
Na+) C14H16O4 271.0941, found 271.0945.
was purified by chromatography (hexanes/EtOAc, 15:1) to yield
20 (441 mg, 87%, E/Z 1:3) as a colorless oil: Rf 0.16 (hexanes/
EtOAc, 10:1); 1H NMR (500 MHz, CDCl3, δ) 8.05-8.04 (m, 2 H),
7.62-7.28 (m, 8 H), 5.53-5.47 (m, 3 H), 4.67-4.60 (m, 2 H),
4.30-4.25 (m, 1 H), 3.97-3.93 (m,1 H), 3.68 (dd, 1 H, J ) 6.5,
9.9 Hz), 3.58 (dd, 1 H, J ) 4.8, 10.0 Hz), 2.63-2.54 (m 3 H),
2.24-1.93 (m, 3 H), 1.05 (t, 3 H, 7.5 Hz); 13C NMR (125.7 MHz,
CDCl3, δ) 166.2, 138.5, 136.2, 134.6, 133.5, 133.,4 130.8, 130.5,
128.9, 128.8, 128.4, 128.1, 127.1, 124.1, 82.6, 77.0, 75.0, 74.6,
73.8, 73.7, 73.0, 72.6, 67.2, 39.4, 36.6, 27.7, 21.5, 21.0, 14.9, 14.8;
HRMS (ESI) calcd for (M + Na+) C24H28O4 381.2060, found
381.2072.
5-H y d r o x y m e t h y l-2-p e n t y l-3-p h e n y lc a r b o n y lo x y -
(2S,3S,5S)-tetr a h yd r ofu r a n (21). To a solution of 20 (400 mg,
1.05 mmol) in CH3OH (10 mL) was added 10% Pd/C (10 mg).
The reaction mixture was stirred under an atmosphere of H2
for 6 h and then filtered through Celite. The filtrate was
concentrated to provide 21 (280 mg, 91%) as a colorless oil: Rf
0.29 (hexanes/EtOAc, 6:1); [R]D +24.8 (c 1.0, CHCl3); 1H NMR
(500 MHz, CDCl3, δ) 8.08 (dd, 2 H, J ) 1.1, 8.2 Hz), 7.61 (dd, 1
H, J ) 7.4, 7.5 Hz), 7.48 (dd, 2 H, 7.88, 13.9 Hz), 5.55-5.52 (m,
1 H), 4.19-4.15 (m, 1 H), 3.95-3.92 (m, 1 H), 3.80 (dd, 1 H, J )
3.17, 11.5 Hz), 3.66 (dd, 1 H, J ) 5.7, 11.5 Hz), 2.55 (dddd, 1 H,
J ) 6.5, 8.6, 8.7, 14.5 Hz), 1.98 (dddd, 1 H, J ) 1.6, 5.7, 5.7, 7.4
Hz), 1.79-1.69 (m, 2 H), 1.52-1.28 (m, 6 H), 0.92 (t, 3 H, J )
7.0 Hz); 13C NMR (125.7 MHz, CDCl3, δ) 166.3, 133.5, 130.4,
129.9, 128.8, 82.9, 78.3, 75.5, 65.4, 35.6, 32.2, 29.4, 26.3, 22.8,
14.3; HRMS (ESI) calcd for (M + Na+) C17H24O4 293.1747, found
293.1768.
(6S,7S,9S,10R/S)-6,9-Ep oxyn on a d ec-18-en e-7-O-ben zoyl-
10-ol (22). Oxalyl chloride (120 µL) was dissolved in CH2Cl2 (10
mL), the mixture was cooled to -78 °C, and a solution of DMSO
(100 µL, 1.37 mmol) in CH2Cl2 (2 mL) was added over the course
of 10 min. Alcohol 21 (200 mg, 0.68 mmol) dissolved in CH2Cl2
(3 mL) was then added dropwise over the course of 5 min, and
the resulting cloudy solution was stirred for 40 min at -78 °C.
Triethylamine (0.3 mL, 2.04 mmol) was added slowly, and the
reaction was allowed to stir for 15 min. The reaction mixture
was then diluted with water and CH2Cl2. The organic layer was
separated and washed with water, dried, filtered, and evaporated
to yield the crude aldehyde, which was dried under vacuum for
1 h.
To a solution of the crude aldehyde in THF (15 mL) at -40
°C was added nonenylmagnesium bromide,10 freshly prepared
from nonenyl bromide (275 mg, 1.36 mmol) and magnesium (49
mg, 2.04 mmol) in dry diethyl ether (30 mL). The reaction
mixture was allowed to stir for 4 h at room temperature before
a saturated aqueous solution of NH4Cl (10 mL) was added. To
the mixture was added EtOAc, and the organic layer was dried
and evaporated. The compound was purified by column chro-
matography (10:1 hexanes/EtOAc) to yield 22 (214 mg, 75%) as
an inseparable mixture of isomers as an oil: Rf 0.55 (hexanes/
EtOAc, 10:1); 1H NMR (500 MHz, CDCl3, δ) 8.10-8.05 (m, 2 H),
7.62-7.30 (m, 3 H), 5.85-5.82 (m, 1 H), 5.53-5.05 (m, 1 H), 5.04
(m, 2 H), 3.96-3.86 (m, 4 H), 2.40-2.05 (m, 4 H), 1.75-1.32 (m,
22 H), 0.89 (dd, 3 H, J ) 6.7, 6.7 Hz); 13C NMR (125.7 MHz,
CDCl3, δ) 166.4, 139.6, 133.6, 133.5, 130.5, 129.9, 128.9, 114.5,
82.5, 81.0, 80.9, 75.7, 74.4, 72.4, 36.4, 34.,2 34.0, 33.1, 32.9, 32.4,
32.3, 29.9, 29.8, 29.7, 29.4, 29.3, 29.2 (2), 26.4, 26.3, 26.2, 26.0,
22.9, 22.9 (2), 14.3; HRMS (ESI) calcd for (M + Na+) C26H40O4
439/2819, found 439.2808.
(3aS,5S,6aS)-5-Hydr oxym eth ylper h ydr ofu r o[3,2-b]fu r an -
2-on e (18). To a solution of 17 (320 mg, 1.29 mmol) in CH3OH
was added 10% Pd/C (10 mg). The reaction mixture was stirred
under an atmosphere of H2 for 5 h and then filtered through
Celite. Concentration of the filtrate afforded 18 (203 mg, 100%)
as a colorless oil: Rf 0.20 (hexanes/EtOAc, 2:1); [R]D +15.3 (c
1
0.7, CHCl3); H NMR (400 MHz, CDCl3, δ) 5.05 (ddd, 1 H, J )
1.7, 4.2, 6.3 Hz), 4.63 (dd, 1 H, J ) 3.2, 7.3 Hz), 4.18 (ddd, 1 H,
J ) 3.2, 7.2, 10.4 Hz), 3.74 (dd, 1 H, J ) 3.2, 11.9 Hz), 3.60 (dd,
1 H, J ) 6.3, 11.8 Hz), 2.75 (d, 2 H, J ) 3.2 Hz), 2.39 (ddd, 1 H,
J ) 6.9, 7.8, 14.6 Hz), 2.12 (ddd, 1 H, J ) 3.2, 7.1, 14.6 Hz), 2.04
(br s, 1 H); 13C NMR (100 MHz, CDCl3, δ) 175.2, 84.4, 80.7, 79.0,
64.6, 36.4, 34.0; HRMS (ESI) calcd for (2M + Na+) C7H10O4
339.1050, found 339.1048
(3a S ,5S ,6a S )-5-t er t -B u t y ld ip h e n y ls ilo x y m e t h y lp e r -
h yd r ofu r o[3,2-b]fu r a n -2-on e (19). To a solution of 18 (180 mg,
1.13 mmol) in dry DMF (5 mL) was added imidazole (200 mg,
2.90 mmol) followed by tert-butylchlorodiphenylsilane (406 mg,
1.47 mmol). The mixture was stirred for 6 h at room tempera-
ture, and then brine (10 mL) was added. The resulting mixture
was extracted with CH2Cl2, and the organic layer was washed
with water, dried, and evaporated. The compound was purified
by chromatography (hexanes/EtOAc, 3:1) to yield 19 (414 mg,
91%) as a white solid: Rf 0.38 (hexanes/EtOAc, 2:1); [R]D -26.0
1
(c 1.5, CHCl3); mp ) 38-39 °C; H NMR (500 MHz, CDCl3, δ)
7.72-7.69 (m, 4 H), 7.45-7.41 (m, 4 H), 5.06 (m, 1 H), 4.62 (ddd,
1 H, J ) 1.9, 4.4, 6.3 Hz), 4.21-4.16 (m, 1 H), 3.80-3.73 (m, 2
H), 2.76 (d, 2 H, J ) 1.6 Hz), 2.42 (ddd, 1 H, J ) 1.6, 7.4, 14.5
Hz), 2.26 (dddd, 1 H, J ) 3.4, 7.2, 7.3, 14.5 Hz) 1.12 (s, 9 H); 13
C
NMR (125.7 MHz, CDCl3, δ) 175.7, 136.1, 136.0, 133.8, 133.7,
130.2, 128.1, 84.8, 81.1, 79.3, 66.0, 36.9, 35.1, 27.2, 19.7(3);
HRMS (ESI) calcd for (M + Na+) C23H28O4Si 419.1649, found
419.1686.
(6S,7S,9S,10S)-6,9-Epoxyn on adec-18-en e-7,10-diol (1) an d
(6S,7S,9S,10S)-6,9-Ep oxyn on a d ec-18-en e-7,10-d iol (3). To a
solution of 22 (200 mg, 0.48 mmol) in THF (10 mL) were added
triphenylphosphine (188 mg, 0.72 mmol) and benzoic acid (86
mg, 0.72 mmol). The solution was cooled to 0 °C, and diisoprop-
ylazodicarboxylate (0.19 mL, 0.96 mmol) was added dropwise
over a period of 5 min. The reaction mixture was warmed to
room temperature and stirred for 2 h. The solution was then
concentrated to dryness, and the residue was purified by column
chromatography (10:1 hexane/EtOAc) to obtain 23. Dibenzoate
23 was dissolved in methanol (10 mL), and 1 M NaOMe in
MeOH (1 mL) was added. After being stirred for 3 h at room
temperature, the reaction mixture was neutralized with Am-
berlite IR-120 (H+) resin, filtered, and concentrated. Purification
by chromatography (hexanes/EtOAc, 6:1) yielded a 4:1 ratio of
1 and 3 (116 mg, 77% combined yield from 22).
5-Ben zyloxym eth yl-2-[(E/Z)-2-pen ten yl]-3-ph en ylcar bon -
yloxy-(2S,3S,5S)-tetr a h yd r ofu r a n (20). To a stirred suspen-
sion of n-propyltriphenylphosphonium bromide (1.52 g, 3.95
mmol) in THF (40 mL) at 0 °C was added sodium amide (14
mg, 3.68 mmol). The mixture was stirred for 12 h at room
temperature under an atmosphere of argon. Separately, alkene
11 (0.480 g, 1.36 mmol) was oxidized to the corresponding
aldehyde as described for the preparation of 15, except that the
product was not purified following the final evaporation step.
Instead, the aldehyde was immediately dissolved in THF (20
mL) and cooled to -20 °C, before the orange ylide solution was
added. After the mixture was stirred for 1 h, an aqueous
saturated solution of NH4Cl was added followed by ether. The
organic layer was dried and concentrated, and the compound

Notes
1: white solid; Rf 0.26 (hexanes/EtOAc, 10:1); [R]D +24.3 (c
J . Org. Chem., Vol. 66, No. 26, 2001 9051
26: Rf 0.60 (hexanes/EtOAc, 10:1); [R]D +6.6 (c 0.3 CHCl3);
1H NMR (500 MHz, CDCl3, δ) 5.83 (dddd, J ) 6.7, 6.7, 10.2, 13.4
Hz), 5.29-5.26 (m, 1 H), 5.03 (dd, 1 H, J ) 1.1, 17.1 Hz), 4.99
(d, 1 H, J ) 10.1 Hz), 4.20 (ddd, 1 H, J ) 2.5, 7.2, 7.2 Hz), 4.08
(ddd, 1 H, J ) 3.3, 7.4, 7.5 Hz), 3.93-3.90 (m, 1 H), 2.42 (ddd,
1 H, J ) 7.4, 7.6, 14.2 Hz), 2.20-2.16 (m, 2 H), 2.10-2.06 (m, 2
H), 1.64-1.30 (m, 22 H), 0.93 (dd, 3 H, J ) 6.4, 6.4 Hz); 13C
NMR (125.7 MHz, CDCl3, δ) 166.7, 139.6, 133.5, 130.4, 130.0,
128.8, 114.6, 84.1, 80.5, 79.2, 72.0, 34.2, 33.2, 32.6, 32.1, 31.2,
30.3, 29.7, 29.5, 29.3, 26.3, 25.8, 22.9, 14.4; HRMS (ESI) calcd
for (M + Na+) C26H40O4 439.2819, found 439.2818.
27: Rf 0.55 (hexanes/EtOAc, 10:1); [R]D +7.6 (c 0.3 CHCl3);
1H NMR (500 MHz, CDCl3, δ) 5.81 (dddd, J ) 6.7, 6.7, 10.2, 13.4
Hz), 5.21 (ddd, 1 H, J ) 4.2, 8.6, 8.7 Hz), 5.00-4.90 (m, 2 H),
4.13 (ddd, 1 H, J ) 3.7, 8.7, 8.8 Hz), 3.97-3.92 (m, 1 H), 3.62-
3.56 (m,1 H), 2.51 (ddd, 1 H, J ) 6.7, 9.2, 17.1 Hz), 2.45 (d, 1 H,
J ) 5.0 Hz), 2.05-2.89 (m, 3 H), 1.56-1.28 (m, 22 H), 0.88 (dd,
3 H, J ) 6.7, 6.7 Hz); 13C NMR (125.7 MHz, CDCl3, δ) 166.2,
139.2, 133.2, 129.9, 129.6, 128.5, 114.1, 83.3, 80.7, 78.9, 73.6,
34.1, 33.8, 33.3, 32.8, 31.7, 29.6, 29.4, 29.1, 28.9, 25.7, 25.4, 22.6,
14.0; HRMS (ESI) calcd for (M + Na+) C26H40O4 439.2818, found
439.2811.
(6R,7S,9S,10S)-6,9-E p oxyn on a d ec-18-en e-7,10-d iol (2).
Compound 2 was prepared from 26 (100 mg, 0.24 mmol) as
described for the preparation of 1 and 3 from 22. Purification
by chromatography (hexanes/EtOAc, 10:1) yielded 2 (59 mg,
79%) as an oil: Rf 0.12 (hexanes/EtOAc, 10:1); [R]D +41.7 (c 0.6
CHCl3); 1H NMR (500 MHz, CDCl3, δ) 5.84 (dddd, 1 H, J ) 6.7,
6.7, 9.3, 16.9 Hz), 5.05 (dd, 1 H, J ) 1.6, 16.9 Hz), 4.98 (d, 1 H,
J ) 10.8 Hz), 4.12-3.86 (m, 5 H), 2.24 (ddd, 1 H, J ) 5.9, 9.3,
14.2 Hz), 2.08 (dd, 2 H, J ) 6.9, 14.4 Hz), 1.91 (dd, 1 H, J ) 2.8,
13.9 Hz), 1.52-1.29 (m, 22 H), 0.93 (dd, 3 H, J ) 6.7, 6.7 Hz);
13C NMR (125.7 MHz, CDCl3, δ) 139.6, 114.6, 87.9, 80.5, 75.4,
72.9, 34.2, 33.7, 33.5, 33.2, 29.5, 29.7, 29.6, 29.3, 26.3, 26.0, 23.0,
14.4; HRMS (ESI) calcd for (M + Na+) C19H36O3 335.2556, found
335.2570.
0.3 CHCl3); mp ) 34-35 °C; 1H NMR (500 MHz, CDCl3, δ) 5.84
(dddd, 1 H, J ) 6.7, 6.7, 12.3, 16.9 Hz), 4.98 (dd 1 H, J ) 1.6,
16.9 Hz), 4.96 (d, 1 H, J ) 9.8 Hz), 4.08 (dd, 1 H, J ) 2.7, 5.4
Hz), 3.98 (dd, 1 H, J ) 5.4, 9.8 Hz), 3.66 (ddd, 1 H, J ) 2.7 6.9,
6.9 Hz), 3.52 (ddd, 1 H, J ) 2.4, 5.2, 8.1 Hz), 2.42 (ddd, 1 H, J
) 5.6, 9.9, 14.1 Hz), 2.05 (dd, 2 H, J ) 6.9, 14.5 Hz), 1.88 (dd, 1
H, J ) 3.5, 14.1, Hz), 1.71-1.30 (m, 22 H), 0.93 (dd, 3 H, J )
6.8, 6.8 Hz); 13C NMR (125.7 MHz, CDCl3, δ) 139.6, 114.6, 84.8,
79.5, 74.4, 72.0, 39.2, 34.8, 34.2, 32.5, 29.9, 29.8, 29.3, 29.3, 26.4,
26.3, 23.0, 14.4; HRMS (ESI) calcd for (M + Na+) C19H36O3
335.2556, found 335.2552.
3: white solid; Rf 0.21 (hexanes/EtOAc, 4:1); [R]D +23.1 (c 1.2
CHCl3); mp ) 73-74 °C; 1H NMR (500 MHz, CDCl3, δ) 5.84
(dddd, 1 H, J ) 6.7, 6.7, 12.3, 17.3 Hz), 5.02 (dd, 1 H, J ) 2.0,
17.3 Hz), 4.97 (dd, 1 H, J ) 1.0, 10.1 Hz), 4.06-4.02 (m, 2 H),
3.87-3.85 (m, 1 H), 3.63 (ddd, 1 H, J ) 2.5, 6.8, 9.3 Hz), 3.40
(br.s, 1 H), 2.65 (br.s, 1 H), 2.22 (ddd, 1 H, J ) 5.4, 9.9, 14.3
Hz), 2.07 (m, 2 H), 1.94 (dd, 1 H, J ) 3.4, 14.1 Hz), 1.76-1.29
(m, 22 H), 0.92 (dd, 1 H, J ) 6.4, 6.4 Hz); 13C NMR (125.7 MHz,
CDCl3, δ) 166.4, 139.6, 133.5, 133.4, 130.6, 129.9, 128.8, 114.6,
82.6, 82.5, 81.0, 80.9, 75.7, 75.5, 74.4, 71.6, 36.4, 34.2, 33.9, 33.1,
33.0, 32.3, 29.9, 29.8, 29.7, 29.4, 29.3, 26.4, 26.3, 26.2, 26.0, 22.9,
14.4; HRMS (ESI) calcd for (M + Na+) C19H36O3 335.2556, found
335.2550.
5-Ben zyloxym et h yl-2-[(E/Z)-2-p en t en yl]-3-p h en ylca r b -
on yloxy-(2R,3S,5S)-tetr a h yd r ofu r a n (24). Alkenes 24 were
prepared from 12 (1.40 g, 3.97 mmol) as described for the
preparation of 20 from 11. The compound was purified by
chromatography (hexanes/EtOAc, 15:1) to yield 24 (1.25 g, 83%,
E/Z 1:8) as a colorless oil: Rf 0.26 (hexanes/EtOAc, 10:1); 1H
NMR (500 MHz, CDCl3, δ) 7.96 (dd, 2 H, J ) 1.1, 8.2 Hz), 7.55
(dd, 1 H, J ) 7.3, 7.4 Hz), 7.43-7.24 (m, 7 H), 5.54-5.40 (m, 2
H), 5.25-5.22 (m, 1 H), 4.60 (d, 1 H, J ) 12.2 Hz), 4.57 (d, 1 H,
J ) 12.2 Hz), 4.40-4.38 (m, 1 H), 4.25 (dddd, 1 H, J ) 3.3, 8.3,
8.4, 11.5 Hz), 3.64 (dd, 1 H, J ) 8.0, 12.4 Hz), 3.52 (dd, 1 H, J
) 6.3, 12.4 Hz), 2.56-2.30 (m, 3 H), 2.10-1.96 (m, 3 H), 0.96 (t,
3 H, J ) 7.0 Hz); 13C NMR (125.7 MHz, CDCl3, δ) 166.5, 138.5,
135.0, 133.5, 130.3, 130.0, 129.9, 128.8, 128.7, 128.1, 123.7, 120.8,
115.7, 84.0, 78.6, 73.7, 72.9, 34.7, 32.3, 31.3, 30.4, 30.1, 23.1,
21.1, 14.5; HRMS (ESI) calcd for (M + Na+) C24H28O4 381.2060,
found 381.2052.
(6R,7S,9S,10R)-6,9-E p oxyn on a d ec-18-en e-7,10-d iol (4).
Compound 4 was prepared from 26 (50 mg, 0.12 mmol) as
described for the preparation of 13 from 11. Purification by
chromatography (hexanes/EtOAc, 6:1) yielded 4 (37 mg, 100%)
as a colorless oil: Rf 0.13 (hexanes/EtOAc, 10:1); [R]D +47.5 (c
1
0.2 CHCl3); H NMR (500 MHz, CDCl3, δ) 5.85 (dddd, 1 H, J )
5-H y d r o x y m e t h y l-2-p e n t y l-3-p h e n y lc a r b o n y lo x y -
(2R,3S,5S)-tetr a h yd r ofu r a n (25). Alcohol 25 was prepared
from 24 (400 mg, 1.05 mmol) as described for the preparation
of 21 from 20. The product 25 (289 mg, 94%) was obtained as a
colorless oil: Rf 0.31 (hexanes/EtOAc, 6:1); [R]D +38.0 (c 1.0,
CHCl3); 1H NMR (500 MHz, CDCl3, δ) 8.05 (dd, 2 H, J ) 1.1,
8.2 Hz), 7.61 (dd, 1 H, J ) 7.3, 7.4 Hz), 7.48 (dd, 2 H, J ) 7.8,
14.2 Hz), 5.29-5.26 (m, 1 H), 4.34-4.29 (m, 1 H), 4.21 (dd, 1 H,
J ) 2.5, 7.7 Hz), 3.77-3.71 (m, 2 H), 2.55 (ddd, 1 H, J ) 7.1,
7.2, 14.0 Hz), 2.10 (br.s, 1 H), 2.00 (dddd, 1 H, J ) 3.0, 5.4, 5.5,
14.0 Hz), 1.62-1.29 (m, 8 H), 0.93 (t, 3 H, J ) 7.0 Hz); 13C NMR
(125.7 MHz, CDCl3, δ) 166.5, 133.6, 130.3, 130.0, 128.8, 84.2,
79.2, 78.3, 65.3, 33.7, 33.2, 32.1, 25.7, 22.9, 14.4; HRMS (ESI)
calcd for (M + Na+) C17H24O4 293.1747, found 293.1763.
(6R,7S,9S,10R)-6,9-E p oxyn on a d ec-18-en e-7-O-b en zoyl-
10-ol (26) a n d (6R,7S,9S,10S)-6,9-Ep oxyn on a d ec-18-en e-7-
O-ben zoyl-10-ol (27). Alcohols 26 and 27 were prepared from
25 (230 mg, 0.78 mmol) as described for the preparation of 22
from 21. The compounds were purified by chromatography
(hexanes/EtOAc, 20:1) to yield a 3:1 ratio of 26 and 27 (249 mg,
76% combined) as colorless oils.
6.7, 6.7, 10.2, 13.2 Hz), 5.03 (dd, 1 H, J ) 1.5, 17.1 Hz), 4.97
(dd, 1 H, J ) 1.1, 10.1 Hz), 4.07-4.00 (m, 2 H), 3.93 (ddd, 1 H,
J ) 1.9, 7.8, 7.9 Hz), 3.54 (ddd, 1 H, J ) 0.5, 7.9, 8.1 Hz), 2.42
(ddd, 1 H, J ) 6.3, 8.9, 14.0 Hz), 1.20-2.06 (m, 2 H), 1.82 (ddd,
1 H, J ) 3.6, 3.7, 13.7 Hz), 1.60-1.30 (m, 22 H), 0.92 (dd, 3 H,
J ) 6.5, 6.5 Hz); 13C NMR (125.7 MHz, CDCl3, δ) 139.6, 114.6,
87.7, 79.9, 75.9, 74.6, 37.7, 34.5, 34.2, 33.7, 32.2, 29.9, 29.8, 29.4,
29.3, 26.3, 26.0, 22.9, 14.4; HRMS (ESI) calcd for (M + Na+)
C19H36O3 335.2556, found 335.2527.
Ack n ow led gm en t. This work was supported by the
National Institutes of Health (AI44045) and the OSU
Spectroscopy Institute. C.S.C. is a recipient of a GAANN
fellowship from the U.S. Department of Education.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra for 1-4, 7-22, and 24-27. This material is available
free of charge via the Internet at http://pubs.acs.org.
J O010830A