Acid-mediated conversion of methylene-interrupted bisepoxides to tetrahydrofurans: A biomimetic transformation

Article abstract of DOI:10.1021/jo971147k

The acid-mediated transformation of syn and anti methylene interrupted cis,cis and cis,trans bisepoxides to tetrahydrofurans is high yielding, and demonstrates both regioselectivity and stereoselectivity. Trans,trans methylene interrupted bisepoxides do not yield tetrahydrofurans under the same conditions.

Full text of DOI:10.1021/jo971147k

J . Org. Chem. 1998, 63, 75-83
75
Acid -Med ia ted Con ver sion of Meth ylen e-In ter r u p ted Bisep oxid es
to Tetr a h yd r ofu r a n s: A Biom im etic Tr a n sfor m a tion
Robert J . Capon* and Russell A. Barrow
School of Chemistry, University of Melbourne, Parkville Victoria 3052, Australia
Received J une 24, 1997X
The acid-mediated transformation of syn and anti methylene interrupted cis,cis and cis,trans
bisepoxides to tetrahydrofurans is high yielding, and demonstrates both regioselectivity and
stereoselectivity. Trans,trans methylene interrupted bisepoxides do not yield tetrahydrofurans
under the same conditions.
Substituted tetrahydrofurans feature in many biologi-
cally potent natural products, such as the polyether
antibiotics and annonaceous acetogenins. The latter is
an emerging class of bioactive natural products which
exhibit a host of promising biological properties including
antitumor, antimalarial, antimicrobial, immunosuppres-
sant, antifeedant, and pesticidal activity.1 To fully
exploit the opportunities offered by these compounds
requires access to synthetic methodology capable of
targeting chiral substituted tetrahydrofurans.2 While
early efforts in this direction focused on the purely
synthetic option, more recent contributions have empha-
sized the value of biomimic solutions. The polyepoxide
cyclization cascade, for example, has been recognized as
an efficient biomimetic route to complex chiral tetrahy-
drofuranyl systems.3 Although ethylene-interrupted bise-
poxides have been acknowledged as biosynthetic and
biomimetic precursors to tetrahydrofurans, the potential
of methylene-interrupted bisepoxides has received less
attention.
sion of the polyepoxide cyclization cascade mentioned
above. Our attempts to unravel the relative stereochem-
istry of these epoxylipids led to a detailed study of the
biomimetic transformation of methylene-interrupted bise-
poxides into tetrahydrofurans. The prospects that this
methodology might return an efficient route to a large
array of synthetic tetrahydrofuran analogues was espe-
cially attractive, given the discovery that epoxylipids from
Notheia anomala exhibited potent in vitro anthelmintic
activity.8 This report details the results of our investiga-
tions into the acid-mediated transformation of methylene-
interrupted bisepoxides into tetrahydrofurans, culminat-
ing in a mechanistic model that satisfies the observed
regiochemical and stereochemical outcomes.
Resu lts a n d Discu ssion
Syn a n d An t i Met h ylen e In t er r u p t ed Cis,Cis
Bisep oxid es. The model system chosen for these studies
was prepared as shown in Scheme 1. Commercially
available 1-heptyne (2) was lithiated with n-butyllithium
to afford the acetylide which was immediately reacted
with solid paraformaldehyde to yield 2-octyn-1-ol (3)
(94%). Hydrogenation of 3 with Lindlar catalyst returned
the allylic alcohol 4 (90%), which was converted to the
volatile chloride 5 (75%) via treatment of an intermediate
tosylate with LiCl. The methylene-interrupted C15 enyne
6 was formed (82%) by coupling 5 with 1 equiv of 2 using
conditions similar to those described by J effery.9 Epoxi-
dation of 6 with freshly purified m-CPBA provided the
propargylic epoxide 7 (88%), which was selectively re-
duced with Lindlar catalyst to the allylic epoxide 8 (72%).
Treatment of 8 with m-CPBA yielded a mixture (1:1.2)
of the methylene-interrupted bisepoxides 9 and 10 (82%),
which were resolved by normal phase silica HPLC and
distinguished by spectroscopic analysis. The 1H NMR
multiplicity for 8-H2 proved diagnostic in distinguishing
between the syn 9 (AB: δ 1.73, ddd, 14.4, 5.9, 5.9 Hz and
δ 1.81, ddd, 14.4, 6.8, 6.8 Hz) versus anti 10 (A2: δ 1.73,
t, 16.2 Hz) diastereomers. The two diastereomers 9 and
10 were used as model compounds to investigate the acid-
Our interest in this field came about during investiga-
tions into the chemistry of the southern Australian
marine brown alga Notheia anomala, which yielded an
array of novel epoxylipids,4-7 exemplified by the dihy-
droxytetrahydrofuran 1 and accompanying methylene-
interrupted bisepoxides, trisepoxides and tetraepoxides.
In this regard a natural methylene-interrupted bis-
epoxide cometabolite appeared to be a potential biosyn-
thetic precursor to the tetrahydrofuran 1 and related
metabolitessproceeding via a somewhat truncated ver-
* To whom correspondence should be addressed: Ph +61 3 9344
6468. Fax +61 3 9347 5180, E-mail r.capon@chemistry.unimelb.edu.au.
X Abstract published in Advance ACS Abstracts, December 15, 1997.
(1) Rupprecht, J . K.; Hui, Y.-H.; McLaughlin, J . L. J . Nat. Prod.
1990, 53, 237.
(2) Boivin, T. L. B. Tetrahedron 1987, 43, 3309.
(3) O’Hagan, D. Nat. Prod. Rep. 1989, 6, 205.
(4) Warren, R. G.; Wells, R. J .; Blount, J . F. Aust. J . Chem. 1980,
33, 891.
(5) Barrow, R. A.; Capon, R. J . Aust. J . Chem. 1990, 43, 895.
(6) Murray, L. M.; Barrow, R. A.; Capon, R. J . Aust. J . Chem. 1991,
44, 843.
(8) Some 30+ natural and 80+ synthetic and semisynthetic epoxy-
lipids have been evaluated for in vitro anthelmintic activity. Selected
compounds have also been subjected to in vivo screening in both
laboratory animal models, as well as commercial and domestic
livestock. The SAR analysis of these studies will be published
elsewhere.12
(7) Rochfort, S.; Murray, L. M.; Capon, R. J . J . Nat. Prod. 1992, 55,
1332.
(9) J effery, T. Tetrahedron Lett. 1989, 30, 2225.
S0022-3263(97)01147-X CCC: $15.00 © 1998 American Chemical Society
Published on Web 01/09/1998

76 J . Org. Chem., Vol. 63, No. 1, 1998
Sch em e 1. Syn th esis of Cis,Cis Bisep oxid e Mod el Com p ou n d sa
Capon and Barrow
a
(a) (i) n-BuLi, Et2O; (ii) (CH2O)n, THF; (b) H2, Lindlar catalyst, EtOH, quinoline (cat.); (c) (i) n-BuLi, Et2O/HMPA (3:1); (ii) p-TsCl;
(iii) LiCl; (d) 1-heptyne, K2CO3, TBAC, CuI, DMF; (e) m-CPBA, CH2Cl2. Note: 7-10 are racemic.
terminology is used to differentiate between C-7/C-9 and
C-6/C-10 epoxy carbons, respectively). While the inter-
mediate derived from endo attack undergoes cyclization
to yield tetrahydrofurans directly, that derived from exo
attack undergoes intramolecular transesterification of the
acetate moiety to the adjacent alcohol followed by cy-
clization. The result of this latter process is that exo
nucleophilic attack on the syn cis,cis bisepoxide 9 leads
to the same product as that derived from endo attack on
the anti cis,cis bisepoxide 10 while exo nucleophilic attack
on the anti cis,cis -bisepoxide 10 leads to the same
product as that derived from endo attack on the syn
cis,cis bisepoxide 9.
F igu r e 1. Products from the cyclization of syn and anti cis,cis
bisepoxides (note: 11-14 are racemic).
mediated rearrangement of methylene interrupted cis,cis
bisepoxides to dihydroxytetrahydrofurans.
Treatment of the syn isomer 9 at 90 °C overnight (15
h) in glacial AcOH followed by aqueous workup yielded
as major and minor products the trans tetrahydrofuran
acetate 11 (69%) and the cis tetrahydrofuran acetate 12
(19%) respectively (Figure 1). Identical treatment of the
anti isomer 10 yielded as major and minor products the
cis tetrahydrofuran acetate 12 (66%) and the trans
tetrahydrofuran acetate 11 (22%). Characteristic frag-
ment ions in the EI mass spectra of 11 and 12 (C-9/C-10
cleavage, m/z 199) confirmed placement of the acetate
functionality on the tetrahydrofuran ring. Treatment of
the acetates with methanolic ammonium hydroxide
returned a quantitative yield of the respective dihydrox-
ytetrahydrofurans 13 and 14. The relative stereochem-
istry in 13 was determined by spectroscopic comparison
with the natural product 1 which had previously been
confirmed by X-ray analysis.4 The relative stereochem-
istry for 14 was determined by NOE measurements and
consideration of the proposed mechanistic pathway (Fig-
ure 2), which accounts for both major and minor cycliza-
tion products. In this mechanistic proposal the initial
nucleophilic attack is biased in favor of endo (75-80%)
versus exo (20-25%) epoxy carbons (endo and exo
Syn a n d An ti Meth ylen e-In ter r u p ted Cis,Tr a n s
Bisep oxid es. The model system chosen for these studies
was prepared as shown in Scheme 2. The propargylic
alcohol 3 prepared as described above was reduced with
lithium aluminum hydride to the trans allylic alcohol 15
(85%) and sequentially transformed as per the methodol-
ogy described in Scheme 2 to 16 (76%), 17 (79%), 18
(86%), 19 (88%), and finally to a mixture (1:1.3) of 20
and 21 (81%). The syn and anti diastereomeric cis,trans
bisepoxides 20 and 21 were resolved by normal phase
silica HPLC and distinguished by spectroscopic analysis.
As with 9 and 10, the 1H NMR multiplicity for 8-H2
proved diagnostic in distinguishing between the syn 20
(AB: δ 1.70, ddd, 14.5, 6.8, 5.1 Hz and δ 1.77, ddd, 14.5,
7.3, 4.6 Hz) versus anti 21 (A2: δ 1.82, bt, 5.1 Hz)
diastereomers.
Treatment of the syn isomer 20 at 100 °C overnight
(24 h) in glacial AcOH followed by aqueous workup
yielded as major and minor products the trans tetrahy-
drofuran acetate 22 (70%) and the cis tetrahydrofuran

A Biomimetic Transformation
J . Org. Chem., Vol. 63, No. 1, 1998 77
F igu r e 2. Proposed mechanism for cyclization of syn and anti cis,cis bisepoxides.
Sch em e 2. Syn th esis of Cis,Tr a n s Bisep oxid e Mod el Com p ou n d sa
a
(a) LiAlH4, THF; (b) (i) n-BuLi, Et2O/HMPA (3:1); (ii) p-TsCl; (iii) LiCl; (c) 1-heptyne, K2CO3, TBAC, CuI, DMF; (d) m-CPBA, CH2Cl2;
(e) H2, Lindlar catalyst, EtOH, quinoline (cat.). Note: 18-21 are racemic.
acetate 23 (20%) respectively (Figure 3). Identical treat-
ment of the anti isomer 21 yielded as major and minor
products the cis tetrahydrofuran acetate 23 (68%) and
the trans tetrahydrofuran acetate 22 (19%). Character-
istic fragment ions in the EI mass spectra of both 22 and
23 (C-9/C-10 cleavage, m/z 199) confirmed placement of
the acetate functionality on the tetrahydrofuran ring. Not
withstanding the potential for intramolecular transes-
terification to influence the product distribution, nucleo-
philic attack at either endo or exo carbons of both cis and
trans epoxides can generate four isomeric tetrahydrofu-
ran products. The observation of only two products in
each reaction suggests that nucleophilic attack on 20 and
21 was more regioselective than that observed for 9 and
10. Treatment of the acetates 22 and 23 with methanolic
ammonium hydroxide returned a quantitative yield of the
respective dihydroxytetrahydrofurans 24 and 25. The
relative stereochemistry for 24 was indicated by NOE

78 J . Org. Chem., Vol. 63, No. 1, 1998
Capon and Barrow
consumption of starting material to yield a complex
mixture of “acetates” for which spectroscopic analysis
failed to reveal any evidence of tetrahydrofurans.
Although literature precedent suggests that acid treat-
ment of methylene interrupted bisepoxides lacks specific-
ity and leads to a complex array of products,10 the current
study reveals this not to be the case. Acid treatment
(glacial AcOH, 15 h, 90 °C) of both syn and anti meth-
ylene interrupted cis,cis and cis,trans bisepoxides results
in high yields of tetrahydrofurans (isolable >85%) with
no trace of nontetrahydrofuran byproducts. This acid-
mediated transformation displays both regioselectivity
and stereoselectivity. In all cases initial nucleophilic
attack takes place predominantly (75-80%) at the endo
carbon of a cis epoxide, with a minor product (20-25%)
arising from attack at the exo carbon. While endo attack
intermediates proceed directly to tetrahydrofurans, the
intermediates derived from exo attack undergo intramo-
lecular transesterification prior to cyclization to tetrahy-
drofurans. Trans,trans methylene interrupted bisep-
oxides do not undergo acid-mediated conversion to
tetrahydrofurans under these conditions. The reaction
pathway from bisepoxides to tetrahydrofurans as de-
scribed in this report has potential application in the
synthesis of key functional units in important bioactive
molecules. To illustrate this potential, we have success-
fully applied this methodology to the biomimetic synthe-
sis of novel epoxylipids from the southern Australian
marine brown alga Notheia anomala,11 and to the prepa-
ration of a large number of synthetic analogues for SAR
studies.12 Further to the marine theme, this process is
also descriptive of the possible intramolecular transfor-
mation between the sponges metabolites fijianolide A (30)
and B (31)13 (a stepwise intramolecular nucleophilic
addition to the cis epoxide of a methylene interrupted
cis,trans bisepoxide precursor), and of the possible bio-
synthetic origins of the red algal oxylipid (32)14 (intramo-
lecular nucleophilic addition to a methylene interrupted
cis,cis bisepoxide precursor). This investigation clearly
demonstrates the potential of methylene interrupted
bisepoxides as biosynthetic and biomimetic precursors to
chiral substituted tetrahydrofurans.
F igu r e 3. Products from the cyclization of syn and anti
cis,trans bisepoxides (note: 22-25 are racemic).
difference experiments and spectroscopic comparison to
26, prepared by selective epimerisation of the natural
product 14 (oxidation to the 10-oxo analogue followed by
reduction to yield C-10 epimers separable by HPLC). The
relative stereochemistry for 25 was apparent from NOE
measurements that confirmed 6-H, 7-H, and 9-H as resid-
ing on the same face of the tetrahydrofuran ring, and
through consideration of the proposed mechanism (Figure
4), which accounts for both major and minor cyclization
products. In this mechanistic proposal the initial nu-
cleophilic attack is totally selective for the cis rather than
trans epoxide. Furthermore, as detailed above for cis,cis
bisepoxides, initial nucleophilic attack is biased in favor
of endo (C-7) (78-79%) versus exo (C-6) (21-22%) epoxy
carbons, with the intermediate derived from endo attack
undergoing cyclization to yield tetrahydrofurans directly,
and that from exo attack proceeding via intramolecular
transesterification to tetrahydrofurans.
Syn an d An ti Meth ylen e-In ter r u pted Tr an s,Tr an s
Bisep oxid es. The transformation described above was
successfully extended to the syn and anti bisepoxides
derived from cis,cis-linoleic acid in a biomimetic synthesis
of N. anomala metabolites and subsequent SAR inves-
tigations.8 Consequently the model system selected to
study the reaction of syn and anti trans,trans bisepoxides
was that derived from the commercially available tran-
s,trans-methyl linoleate (27). Epoxidation of 27 with
m-CPBA yielded a mixture of two trans,trans bisepoxides
28 and 29 (100%). Although inseparable by HPLC,
spectroscopic data was consistent with the formation of
(10) Kuranova, I. L.; Gordienko, S. L.; Korskaya, G. N.; Filonova,
E. B. Zh. Org. Khim. 1976, 12, 1699.
(11) Capon, R. J .; Barrow, R. A.; Skene, C.; Rochfort, S. Tetrahedron
Lett. 1997, 37, in press.
(12) Capon, R. J .; Barrow, R. A.; Rochfort, S.; J obling, M. F.; Skene,
C.; Lacey, E.; Friedel, T.; Wadsworth, D. Tetrahedron 1997, submitted.
(13) Quinoa, E.; Kakou, Y.; Crews, P. J . Org. Chem. 1988, 53, 3642.
(14) Furusaki, A.; Kurosawa, E.; Fukusawa, A.; Irie, T. Tetrahedron
Lett. 1973, 14, 4579.
1
bisepoxides, and discrete H NMR resonances for 8-H2
could be observed consistent with a 1:1 mixture of both
syn and anti isomers. This product distribution was
confirmed by GC analysis. Treatment of this mixture
under the acid conditions described above resulted in

A Biomimetic Transformation
J . Org. Chem., Vol. 63, No. 1, 1998 79
F igu r e 4. Proposed mechanism for cyclization of syn and anti cis,trans bisepoxides to tetrahydrofurans.
developed a clear red color which dissipated upon addition of
Exp er im en ta l Section
p-toluenesulfonyl chloride (790 mg, 4.1 mmol) to return a clear
pale yellow solution. LiCl (800 mg, excess) was added and the
reaction mixture allowed to stir for a further 40 h after which
time it was diluted with Et2O (50 mL) and washed with dilute
aqueous HCl (50 mL, 1 M) followed by H2O (3 × 50 mL) and
the organic layer dried over anhydrous MgSO4 and concen-
trated in vacuo to yield starting material 4 (238 mg, 45%) and
5 (250 mg, 75%*) as a mobile, volatile, colorless oil: (* yield
based on reaction proceeding to 55% completion.): 1H NMR
(400 MHz, CDCl3) δ 0.88 (t, J ) 7.1 Hz, 8-H3), 1.2-1.4 (bm, 6,
7-H2), 1.39 (tt, J ) 7.1, 7.1 Hz, 5-H2), 2.11 (dt, J ) 6.8, 7.1 Hz,
4-H2), 4.10 (d, J ) 6.8 Hz, 1-H2), 5.63 (m, 2-H and 3-H); 13C
NMR (100 MHz, CDCl3) 14.0 (C-8), 22.5 (C-7), 27.0 (C-4), 29.0
(C-5), 31.4 (C-6), 39.5 (C-1), 125.0 (C-2), 135.6 (C-3) ppm; EIMS
(70 eV, m/z, %) 148 (M+, 37Cl, 4), 146 (M+, 35Cl, 12), 113 (4),
111 (11), 97 (16), 95 (13), 81 (31), 71 (26), 70 (56), 69 (56), 68
(30), 67 (34), 56 (58), 55 (50), 54 (100).
Gen er a l Meth od s. See ref 15. 2-Octyn -1-ol (3). 1-Hep-
tyne (2) (13.8 mL, 0.1 mol) was added slowly to a stirred
solution of Et2O (80 mL) and n-BuLi (45 mL as a 2.34 M
solution in hexanes, 0.1 mol) under anhydrous conditions at
-10 °C. To the resultant acetylide was added a suspension
of paraformaldehyde (3.6 g, excess) in THF (100 mL), and the
gelantinous mixture allowed to stir at ∼0 °C for 45 min after
which time it was heated to reflux for a further 90 min. The
reaction mixture was then cooled to room temperature, poured
into ice/water (300 mL), and extracted with Et2O (2 × 150 mL).
The combined organic extracts were dried over anhydrous
MgSO4, and the solvent was removed in vacuo to give a yellow
oil which was distilled to yield 3 as a colorless mobile oil (12.3
g, 94%): bp 75-76 °C/12 mmHg; IR (film) νmax 3330, 2285
cm-1; 1H NMR (400 MHz, CDCl3) δ 0.88 (t, J ) 7.1 Hz, 8-H3),
1.25-1.40 (bm, 6-H2 and 7-H2), 1.49 (tt, J ) 7.1, 7.1 Hz, 5-H2),
1.86 (bs, OH), 2.19 (tt, J ) 7.1, 2.4 Hz, 4-H2), 4.23 (dt, J ) 6.8,
2.4 Hz, 1-H2); 13C NMR (100 MHz, CDCl3) 13.8 (C-8), 18.6 (C-
4), 22.1 (C-7), 28.2 (C-5), 30.9 (C-6), 51.1 (C-1), 78.2 (C-2), 86.3
(C-3) ppm; EIMS (70 eV, m/z, %) 111 (M+ - CH3), 97 (14), 95
(100), 83 (52), 71 (15), 69 (33), 57 (17), 55 (71), 43 (24); CIMS
(isobutane, 20 eV, m/z, %) 127 (M + H, 2), 109 (100), 95 (18);
HRMS found 111.0810 (C8H14O (M+ - CH3) requires 111.0809).
(Z)-2-Octen -1-ol (4). A solution of 3 (2.4 g, 0.02 mol) in a
pleated flask with EtOH (30 mL), quinoline (0.25 mL), and
Lindlar’s catalyst (400 mg, 17% w/w) was stirred vigorously
under an atmosphere of H2. After consumption of 1 mol equiv
of H2 the mixture was filtered through a plug of silica to
remove the catalyst and purified by MPLC (silica, 10% EtOAc/
hexane) to yield 4 (2.2 g, 90%) as a colorless mobile oil: IR
(film) νmax 3384, 1598 cm-1; 1H NMR (400 MHz, CDCl3) δ 0.88
(t, J ) 7.0 Hz, 8-H3), 1.3-1.45 (bm, 5, 6, 7-H2), 1.65 (bs, OH),
2.05 (dt, J ) 7.3, 6.4 Hz, 4-H2), 4.18 (bd, J ) 6.1 Hz, 1-H2),
5.54 (dt, J ) 11.0, 7.3 Hz, 3-H), 5.59 (dt, J ) 11.0, 6.1 Hz,
2-H); 13C NMR (100 MHz, CDCl3) 14.0 (C-8), 22.4 (C-7), 27.3,
29.2 (C-5, C-6), 31.3 (C-4), 58.4 (C-1), 128.3 (C-2), 132.9 (C-3)
ppm.
(Z)-6-P en ta d ecen -9-yn e (6). To stirred solution of freshly
distilled DMF (2 mL) at room temperature under an atmo-
sphere of N2 were added in order 1-heptyne (2) (123 µL, 0.94
mmol), K2CO3 (160 mg, 1.16 mmol), tetrabutylammonium
chloride (TBAC) (30 mg, 0.11 mmol), and CuI (8 mg, 0.04
mmol). The resulting mixture was stirred for 10 min and then
treated with 5 (120 mg, 0.82 mmol) as a solution in DMF (0.5
mL) after which it was warmed to 40 °C and allowed to stir
for a further 48 h. After this time the reaction mixture was
cooled to room temperature and diluted with Et2O (50 mL)
and the organic layer washed with H2O (2 × 50 mL), dilute
aqueous HCl (50 mL, 1 M), brine (50 mL), and finally H2O (50
mL). The ethereal extract was dried over anhydrous MgSO4
and concentrated in vacuo to return a pale yellow oil that was
purified by elution through a silica Sep-pak using hexane as
the eluent to yield 6 (138 mg, 82%) as a colorless mobile oil:
1
IR (film) νmax 1640 cm-1; H NMR (400 MHz, CDCl3) δ 0.88
and 0.89 (2t, J ) 6.8 Hz, 1 and 15-H3), 1.25-1.55 (bm, 2, 3, 4,
12, 13, 14-H2), 2.03 (dt, J ) 7.6, 6.6 Hz, 5-H2), 2.14 (tt. J )
7.1, 2.4 Hz, 11-H2), 2.90 (dt, J ) 5.1, 2.4 Hz, 8-H2), 5.42 (m, 6
and 7-H); 13C NMR (100 MHz, CDCl3) 14.0, 14.1 (C-1 and
C-15), 17.1 (C-8), 18.8 (C-11), 22.2, 22.5 (C-2 and C-14), 27.1
(C-5), 28.7, 29.1 (C-4 and C-12), 31.1, 31.5 (C-3 and C-13), 78.4
(C-9), 80.1 (C-10), 125.0 (C-7), 131.4 (C-6) ppm; EIMS (70 eV,
m/z, %) 206 (M+, 2), 191 (1), 177 (4), 163 (5), 149 (19), 135
(16), 121 (25), 110 (30), 109 (9), 107 (38), 95 (31), 93 (92), 79
(Z)-1-Ch lor o-2-octen e (5). To a stirred solution of 4 (530
mg, 4.1 mmol) in Et2O/HMPA (3:1, 40 mL) under a nitrogen
atmosphere at 0 °C was added n-BuLi (1.75 mL as a 2.4 M
solution in hexane, 4.1 mmol). The initially colorless solution
(15) Murray, L. M.; Lim, T. K.; Currie, G.; Capon, R. J . Aust. J .
Chem. 1995, 48, 1253.

80 J . Org. Chem., Vol. 63, No. 1, 1998
Capon and Barrow
(100), 71 (28), 67 (57), 53 (64), 53 (30); HRMS found 206.2034
(C15H26 requires 206.2036).
H2), 1.52 (m, 5 and 11-H2), 1.73 (t, J ) 6.2 Hz, 8-H2), 2.98 (dt,
J ) 4.2, 6.3 Hz, 6 and 10-H), 3.12 (dt, J ) 4.2, 6.2 Hz, 7 and
9-H); 13C NMR (100 MHz, CDCl3) 14.0 (C-1 and C-15), 22.5
(C-2 and C-14), 26.1, 27.9 (C-4, C-5, C-11 and C-12), 27.2 (C-
8), 31.7 (C-3 and C-13), 54.4 (C-7 and C-9), 57.0 (C-6 and C-10)
ppm; EIMS (70 eV, m/z, %) 183 (1), 175 (2), 169 (2), 165 (5),
157 (7), 139 (8), 127 (4), 123 (5), 113 (14), 96 (30), 84 (39), 83
(6S*,7R*)-6,7-Ep oxyp en ta d ec-9-yn e (7). To a stirred
solution of 6 (85 mg, 0.41 mmol) in CH2Cl2 (10 mL) at 0 °C
was added freshly prepared m-CPBA (99%, 80 mg, 0.46 mmol).
The reaction mixture was allowed to warm to room temper-
ature where it was stirred for 24 h before being diluted with
Et2O (50 mL) and washed with saturated NaHCO3 solution
(2 × 40 mL), dilute aqueous KOH (30 mL, 1 M), and finally
brine (20 mL). The organic layer was dried over anhydrous
MgSO4 and the solvent removed in vacuo to return a mobile
yellow oil which was purified by elution through a silica Sep-
pak using hexane as the eluant to yield 7 (81 mg, 88%) as a
(46), 81 (24), 69 (65), 54 (100); HRMS found 127.1123 (C8H15
requires 127.1122), 113.0966 (C7H13O requires 113.0966).
O
Cycliza tion of (6S*,7R*,9S*,10R*)-6,7:9,10-Bis(ep oxy)
p en ta d eca n e (9). A sample of the syn bisepoxide 9 (8.0 mg,
0.033 mmol) in glacial acetic acid (3 mL) was stirred at 90 °C
for 15 h after which the reaction mixture was diluted with
Et2O (40 mL) and washed with H2O (3 × 40 mL), saturated
NaHCO3 solution (20 mL), and H2O (40 mL). The organic
layer was collected, dried over anhydrous MgSO4, and con-
centrated in vacuo to return a colorless oil (9.2 mg). Chro-
matographic purification by HPLC (silica, 40% EtOAc/hexane
and then 20% EtOAc/hexane) yielded the trans tetrahydrofu-
ran acetate 11 (6.8 mg, 69%) and cis tetrahydrofuran acetate
12 (1.9 mg, 19%), with the trans isomer being slightly less
polar than the cis isomer.
colorless oil: IR (film) νmax 2260 cm-1 1H NMR (400 MHz,
;
CDCl3) δ 0.89 and 0.90 (t, J ) 7.1 Hz, 1 and 15-H3), 1.25-
1.55 (bm, 2, 3, 4, 5, 12, 13, 14-H2), 2.15 (tt, J ) 7.1, 2.4 Hz,
11-H2), 2.24 (ddt, J ) 16.8, 7.3, 2.4 Hz, 8-HA), 2.56 (ddt, J )
16.8, 5.4, 2.4 Hz, 8-HB), 2.95 (ddd, J ) 6.1, 5.9, 4.2 Hz, 6-H),
3.11 (ddd, J ) 7.3, 5.4, 4.2 Hz, 7-H); 13C NMR (100 MHz,
CDCl3) 14.0 (C-1 and C-15), 18.7 (C-8), 18.8 (C-11), 22.2, 22.6
(C-2 and C-14), 26.1, 27.5, 28.6 (C-4, C-5 and C-12), 31.1, 31.7
(C-3 and C-13), 55.5, 57.1 (C-6 and C-7), 74.8, 82.5 (C-9 and
C-10) ppm; EIMS (70 eV, m/z, %) 222 (M+, 1), 221 (M+ - 1, 2),
207 (2), 193 (3), 179 (26), 165 (35), 151 (63), 133 (56), 123 (18),
109 (36), 105 (20), 99 (29), 95 (48), 93 (23), 91 (21), 81 (90), 67
(100), 54 (92); HRMS found 221.1905 (C15H25O requires:
221.1904).
(6S*,7S*,9R*,10R*)-6,9-Epoxypen tadecan e-7,10-diol 7-ac-
1
eta te (11): a colorless oil; IR (film) νmax 3468, 1740 cm-1; H
NMR (400 MHz, CDCl3) δ 0.88 and 0.89 (2t, J ) 7.0 Hz, 1 and
15-H3), 1.3-1.6 (bm, 2, 3, 4, 5, 11, 12, 13, 14-H2), 1.99 (ddd, J
) 13.5, 8.9, 4.5 Hz, 8-HA), 2.03 (ddd, J ) 13.5, 6.9, 1.5 Hz,
8-HB), 2.25 (bs, OH), 3.39 (m, 10-H), 3.89 (ddd, J ) 7.6, 5.9,
3.2 Hz, 6-H), 3.99 (ddd, J ) 8.9, 6.9, 6.3 Hz, 9-H), 5.31 (m,
7-H); 13C NMR (100 MHz, CDCl3) 14.0, 14.1 (C-1 and C-15),
21.0 (COCH3), 22.5, 22.6 (C-2 and C-14), 25.3, 25.9, 29.0, 31.9,
31.9, 33.3 (C-3, C-4, C-5, C-11, C-12 and C-13), 35.6 (C-8), 73.9
(C-10), 75.5 (C-7), 80.4 (C-9), 81.3 (C-6), 170.5 (COCH3) ppm;
EIMS (70 eV, m/z, %) 199 (7), 140 (20), 139 (100), 113 (4), 99
(27), 84 (10).
(6S*,7R*, 9Z)-6,7-ep oxy-9-p en ta d ecen e (8): A solution of
7 (80 mg, 0.36 mmol) in EtOH (10 mL) with quinoline (50 µL)
and Lindlar’s catalyst (20 mg, 25% w/w) was stirred vigorously
under an atmosphere of H2 until uptake ceased (30 min), after
which the reaction mixture was diluted with hexane (20 mL),
filtered through a pad of silica and concentrated in vacuo to
yield 8 (58 mg, 72%) as a colorless mobile oil: IR (film) νmax
1
1453 cm-1; H NMR (400 MHz, CDCl3) δ 0.89 and 0.90 (2t, J
) 7.1 Hz, 1 and 15-H3), 1.2-1.6 (bm, 2, 3, 4, 5, 12, 13, 14-H2),
2.04 (dt, J ) 7.1, 7.1 Hz, 11-H2), 2.18 (bddd, J ) 15.0, 7.3, 5.9
Hz, 8-HA), 2.37 (bddd, J ) 15.0, 7.3, 5.9 Hz, 8-HB), 2.93 (bm,
6-H and 7-H), 5.41 (ddt, J ) 10.7, 7.3, 1.5 Hz, 9-H), 5.52 (ddt,
J ) 10.7, 7.3, 1.5 Hz, 10-H); 13C NMR (100 MHz, CDCl3) 14.1,
14.1 (C-1 and C-15), 22.6, 22.6 (C-2 and C-14), 26.2, 26.3, 27.4,
27.7, 29.2, 31.5, 31.7 (C-3, C-4, C-5, C-8, C-11, C-12 and C-13),
56.6, 57.2 (C-6 and C-7), 123.8, 132.7 (C-9 and C-10) ppm;
EIMS (70 eV, m/z, %) 224 (M+, 1), 206 (1), 193 (3), 181 (2),
167 (3), 153 (10), 139 (5), 124 (6), 113 (24), 111 (11), 110 (21),
109 (10), 99 (11), 97 (15), 96 (15), 95 (31), 93 (10), 84 (17), 81
(56), 69 (72), 68 (54), 67 (71), 56 (28), 54 (100); HRMS found
224.2140 (C15H28O requires 224.2141).
(6S*,7S*,9S*,10S*)-6,9-Epoxypen tadecan e-7,10-diol 7-ac-
1
eta te (12): a colorless oil; IR (film) νmax 3465, 1740 cm-1; H
NMR (400 MHz, CDCl3) δ 0.88 and 0.89 (2t, J ) 6.8 Hz, 1 and
15-H3), 1.3-1.6 (bm, 2, 3, 4, 5, 11, 12, 13, 14-H2), 1.74 (ddd, J
) 14.4, 6.4, 2.0 Hz, 8-HA), 2.06 (COCH3), 2.38 (ddd, J ) 14.4,
8.3, 6.6 Hz, 8-HB), 3.47 (ddd, J ) 7.9, 6.0, 4.2 Hz, 10-H), 3.73
(ddd, J ) 7.8, 5.9, 3.9 Hz, 6-H), 3.76 (ddd, J ) 8.3, 6.4, 6.0 Hz,
9-H), 5.22 (ddd, J ) 6.6, 3.9, 2.2 Hz, 7-H); 13C NMR (100 MHz,
CDCl3) 14.0, 14.1 (C-1 and C-15), 21.1 (COCH3), 22.5, 22.6 (C-2
and C-14), 25.4, 25.9, 28.7, 31.8, 31.8, 33.6 (C-3, C-4, C-5, C-11,
C-12 and C-13), 35.9 (C-8), 73.8 (C-10), 74.7 (C-7), 80.4 (C-9),
81.8 (C-6), 170.6 (COCH3) ppm; EIMS (70 eV, m/z, %) 199 (5),
140 (18), 139 (100), 113 (6), 99 (40), 95 (10), 84 (10).
Bisep oxid es 9 a n d 10. To a stirred solution of 8 (32 mg,
0.14 mmol) at 0 °C was added m-CPBA (99%, 28 mg, 0.016
mmol) and the reaction mixture warmed to room temperature.
After 24 h the reaction mixture was diluted with Et2O (50 mL),
washed with saturated NaHCO3 solution (2 × 30 mL), dilute
aqueous KOH (15 mL, 2 M), and H2O (30 mL), and the ethereal
layer was dried over anhydrous MgSO4 and concentrated in
vacuo to return a crude mixture of the bisepoxides 9 and 10.
Chromatographic purification by HPLC (silica, 5% EtOAc/
hexane) yielded the two bisepoxide diastereomers, with the
syn diastereomer 9 (13 mg, 38%) eluting first followed by the
anti diastereomer 10 (15 mg, 44%): (6S*,7R*,9S*,10R*)-6,7:
9,10-bis(ep oxy)p en ta d eca n e (9): a colorless oil; 1H NMR
(400 MHz, CDCl3) δ 0.90 (t, J ) 7.2 Hz, 1 and 15-H3), 1.34-
1.52 (bm, 2, 3, 4, 12, 13, 14-H2), 1.55 (m, 5 and 11-H2), 1.73
(ddd, J ) 14.4, 5.9, 5.9 Hz, 8-HA), 1.81 (ddd, J ) 14.4, 6.8, 6.8
Hz, 8-HB), 2.97 (dt, J ) 4.4, 6.0 Hz, 6 and 10-H), 3.08 (ddd, J
) 6.8, 5.9, 4.4 Hz, 7 and 9-H); 13C NMR (100 MHz, CDCl3)
14.0 (C-1 and C-15), 22.6 (C-2 and C-14), 26.2, 27.8 (C-4, C-5,
C-11 and C-12), 26.9 (C-8), 31.7 (C-3 and C-13), 54.2 (C-7 and
C-9), 56.8 (C-6 and C-10) ppm; EIMS (70 eV, m/z, %) 199 (2),
194 (11), 187 (20), 131 (33), 127 (5), 117 (30), 113 (12), 91 (54),
Cycliza tion of (6S*,7R*,9R*,10S*)-6,7:9,10-Bis(ep oxy)-
p en ta d eca n e (10): A sample of the anti bisepoxide 10 (7.0
mg, 0.029 mmol) in glacial acetic acid (3 mL) was stirred at
90 °C for 15 h after which the reaction mixture was diluted
with Et2O (40 mL) and washed with H2O (3 × 40 mL),
saturated NaHCO3 solution (20 mL), and H2O (40 mL). The
organic layer was collected, dried over anhydrous MgSO4, and
concentrated in vacuo to return a colorless oil (7.9 mg).
Chromatographic purification by HPLC (silica, 40% EtOAc/
hexane and then 20% EtOAc/hexane) yielded the cis tetrahy-
drofuran acetate 12 (5.7 mg, 66%) and trans tetrahydrofuran
acetate 11 (1.9 mg, 22%).
(6S*,7S*,9R *,10R *)-6,9-E p oxyp e n t a d e ca n e -7,10-d iol
(13): A solution of 11 (4.0 mg, 0.013 mmol) in MeOH (2 mL)
and NH4OH (33% aq solution, 1 mL) was stirred for 5 h at
room temperature after which it was concentrated in vacuo
to yield the trans tetrahydrofuran 13 (3.4 mg, 100%) as a
colorless oil: IR (film) νmax 3413 cm-1 1H NMR (400 MHz,
;
CDCl3) δ 0.89 and 0.90 (2t, J ) 7.1 Hz, 1 and 15-H3), 1.3-1.6
(methylene envelope, 2, 3, 4, 5, 11, 12, 13, 14-H2), 1.87 (ddd, J
) 13.4, 9.0, 4.4 Hz, 8-HA), 2.01 (ddd, J ) 13.4, 6.6, 1.0 Hz,
8-HB), 3.39 (m, 10-H), 3.75 (dt, J ) 2.7, 6.8 Hz, 6-H), 4.02 (ddd,
83 (49), 69 (70), 54 (100); HRMS found 127.1123 (C8H15
O
J ) 9.0, 6.8, 6.6 Hz, 9-H), 4.25 (bdd, J ) 4.4, 2.7 Hz, 7-H); 13
C
requires 127.1122), 113.0966 (C7H13O requires 113.0966).
(6S*,7R*,9R*,10S*)-6,7:9,10-Bis(ep oxy)p en ta d eca n e (10):
a waxy solid; mp 41-43 °C; 1H NMR (400 MHz, CDCl3) δ 0.90
(t, J ) 7.2 Hz, 1 and 15-H3), 1.33-1.5 (bm, 2, 3, 4, 12, 13, 14-
NMR (100 MHz, CDCl3) 14.0, 14.0 (C-1 and C-15), 22.5, 22.6
(C-2 and C-14), 25.3, 26.0, 28.8, 31.9, 32.0, 33.1 (C-3, C-4, C-5,
C-11, C-12 and C-13), 37.9 (C-8), 73.5 (C-7), 74.1 (C-10), 80.2
(C-9), 82.4 (C-6) ppm; EIMS (70 eV, m/z, %) 258 (M+, 1), 240

A Biomimetic Transformation
J . Org. Chem., Vol. 63, No. 1, 1998 81
(1), 222 (1), 201 (2), 187 (3), 169 (3), 157 (57), 139 (34), 121
(12), 114 (21), 113 (69), 95 (65), 83 (28); HRMS found 258.2183
(C15H30O3 (M+) requires 258.2195).
(ddt, J ) 6.8, 6.6, 1.5 Hz, 5-H2), 2.17 (tt, J ) 7.1, 2.4, 11-H2),
2.87 (ddt, J ) 5.5, 2.4, 1.5 Hz, 8-H2), 5.39 (ddt, J ) 15.1, 5.5,
1.5 Hz, 7-H), 5.66 (ddt, J ) 15.1, 6.8, 1.5 Hz, 6-H); 13C NMR
(100 MHz, CDCl3) 14.0 and 14.1 (C-1 and C-15), 18.8 (C-11),
22.0 (C-8), 22.2, 22.5 (C-2 and C-14), 28.8, 29.0 (C-4 and C-12),
31.1, 31.4 (C-3 and C-13), 32.2 (C-5), 77.6 (C-9), 82.1 (C-10),
124.7 (C-7), 131.8 (C-6) ppm; EIMS (70 eV, m/z, %) 206 (M+,
<1), 205 (M+ - 1, 1), 177 (4), 163 (4), 149 (22), 135 (23), 121
(30), 110 (33), 107 (42), 93 (88), 81 (57), 79 (100), 67 (58), 54
(63); HRMS found 205.1956 (C15H25 (M+ - 1) requires 205.1959).
(6R*,7R*)-6,7-Ep oxy-9-p en ta d ecyn e (18). To a solution
of 17 (34 mg, 0.17 mmol) in CH2Cl2 (2 mL) was added freshly
prepared m-CPBA (34.5 mg, 1 equiv) and the mixture stirred
at room temperature for 3 h after which it was extracted into
Et2O (25 mL) and washed with a saturated solution of NaHCO3
(3 × 25 mL), brine, (25 mL), and H2O (25 mL). The organic
phase was collected, dried over anhydrous MgSO4, and con-
centrated in vacuo to return a viscous oil (37 mg) that was
purified by HPLC (silica, 5% EtOAc/hexane) to yield 18 (32
mg, 86%) as a colorless oil: IR (film) νmax 2363 cm-1; 1H NMR
(400 MHz, CDCl3) δ 0.89 (t, J ) 7.1 Hz, 1 and 15-H3), 1.2-1.6
(bm, 2, 3, 4, 5, 12, 13, 14-H2), 2.14 (tt, J ) 7.1, 2.4 Hz, 11-H2),
2.36 (ddt, J ) 17.1, 5.1, 2.4 Hz, 8-HA), 2.57 (ddt, J ) 17.1, 4.2,
2.4 Hz, 8-HB), 2.83 (m, 6 and 7-H); 13C NMR (100 MHz, CDCl3)
14.0 (C-1 and C-15), 18.7 (C-11), 22.3 (C-8), 22.2, 22.6 (C-2 and
C-14), 25.6, 28.6, 31.0, 31.5, 31.6 (C-3, C-4, C-5, C-12 and C-13),
56.6, 58.5 (C-6 and C-7), 74.4, 82.6 (C-9 and C-10) ppm; EIMS
(70 eV, m/z, %) 222 (M+, 2), 221 (M+ - 1, 6), 207 (2), 193 (3),
179 (19), 165 (33), 151 (63), 156 (30), 139 (25), 127 (5), 113 (7),
109 (31), 99 (40), 95 (54), 81 (78), 71 (39), 69 (46), 67 (93), 54
(100); HRMS found 221.1905 (C15H21O (M+ - 1) requires
221.1904).
(6R*,7R*,9Z)-6,7-Ep oxy-9-p en ta d ecen e (19). To a solu-
tion of 18 (32 mg, 0.14 mmol) in EtOH (10 mL) were added
quinoline (50 µL) and Lindlar’s catalyst (15 mg, 47% w/w) and
the resulting mixture vigorously stirred under an atmosphere
of H2 until approximately 1 equiv of H2 had been consumed
(∼6 h). The reaction mixture was then diluted with hexane
(20 mL) and filtered through a pad of silica to return a crude
product that was purified by HPLC (silica, 5% EtOAc/hexane)
to yield 19 (30 mg, 88%) as a colorless oil: IR (film) νmax 1465
cm-1; 1H NMR (400 MHz, CDCl3) δ 0.88 and 0.89 (2t, J ) 7.0
Hz, 1 and 15-H3), 1.2-1.55 (bm, 2, 3, 4, 5, 12, 13, 14-H2), 2.02
(dt, J ) 6.1, 7.2 Hz, 11-H2), 2.21 (bddd, J ) 14.8, 7.4, 7.1 Hz,
8-HA), 2.39 (bddd, J ) 14.8, 7.4, 7.3 Hz, 8-HB), 2.69 (m, 6 and
7-H), 5.38 (dtt, J ) 10.9, 7.3, 1.5, 9-H), 5.51 (dtt, J ) 10.9, 7.3,
1.5 Hz, 10-H); 13C NMR (100 MHz, CDCl3) 14.0, 14.0 (C-1 and
C-15), 22.5, 22.6 (C-2 and C-14), 30.0 (C-8), 25.7, 27.3, 29.2,
31.4, 31.6, 31.9 (C-3, C-4, C-5, C-11, C-12, and C-13), 58.1, 58.5
(C-6 and C-7), 123.3 (C-9), 132.9 (C-10) ppm; EIMS (70 eV,
m/z, %) 224 (M+, 1), 206 (1), 195 (1), 181 (2), 167 (2), 153 (9),
139 (4), 135 (5), 127 (3), 124 (11), 113 (33), 110 (29), 96 (21),
95 (32), 83 (35), 82 (30), 81 (54), 71 (14), 69 (78), 67 (58), 54
(100); HRMS found 224.2140 (C15H28O requires 224.2137).
Ep oxid a tion of (6R*,7R*,9Z)-6,7-Ep oxy-9-p en ta d ecen e
(19). To a solution of the homoallylic epoxide 19 (28 mg, 0.13
mmol) in CH2Cl2 (3 mL) at 0 °C was added m-CPBA (99%, 30
mg, 0.17 mmol). The reaction mixture was then warmed to
room temperature and stirred for 20 h before extraction into
Et2O (25 mL). The organic phase was washed with a saturated
NaHCO3 solution (3 × 20 mL) followed by H2O (25 mL) and
then dried over anhydrous MgSO4 and concentrated in vacuo
to return a colorless oil (26 mg) that was purified by HPLC
(silica, 20% EtOAc/hexane) to yield the diastereomeric bis-
epoxides 20 (11 mg, 35%) and 21 (14.5 mg, 35%) as colorless
oils that readily solidified at low temperature (<0 °C):
(6R *,7R *,9S *,10R *)-6,7:9,10-B is (e p o x y )p e n t a d e c a n e
(20): 1H NMR (400 MHz, CDCl3) δ 0.89 and 0.89 (2t, J ) 7.2
Hz, 1 and 15-H3), 1.3-1.6 (bm, 2, 3, 4, 5, 11, 12, 13, 14-H2),
1.70 (ddd, J ) 14.5, 6.8, 5.1 Hz, 8-HA), 1.77 (ddd, J ) 14.5,
7.3, 4.6 Hz, 8-HB), 2.74 (dt, J ) 2.2, 5.6 Hz, 6-H), 2.86 (ddd, J
) 6.8, 4.6, 2.2 Hz, 7-H), 2.97 (dt, J ) 4.4, 6.2 Hz, 10-H), 3.10
(ddd, J ) 7.3, 5.1, 4.4 Hz, 9-H); 13C NMR (100 MHz, CDCl3)
14.0 (C-1 and C-15), 22.6 (C-2 and C-14), 25.6, 26.1, 27.8, 31.6,
31.6, 31.9 (C-3, C-4, C-5, C-11, C-12 and C-13), 31.3 (C-8), 54.0
(6S*,7S*,9S*,10S*)-6,9-Epoxypen tadecan e-7,10-diol (14).
A solution of 12 (3.8 mg, 0.013 mmol) in MeOH (2 mL) and
NH4OH (33% aq solution, 1 mL) was stirred for 5 h at room
temperature after which it was concentrated in vacuo to yield
the cis tetrahydrofuran 14 (3.3 mg, 100%) as a colorless oil:
1
IR (film) νmax 3400 cm-1; H NMR (400 MHz, CDCl3) δ 0.88
and 0.89 (2t, J ) 7.2 Hz, 1 and 15-H3), 1.3-1.6 (methylene
envelope, 2, 3, 4, 5, 11, 12, 13, 14-H2), 1.84 (dd, J ) 13.9, 3.6
Hz, 8-HA), 2.38 (ddd, J ) 13.9, 9.9, 5.6 Hz, 8-HB), 3.48 (ddd, J
) 7.8, 5.3, 2.4 Hz, 10-H), 3.62 (dt, J ) 2.7, 6.8 Hz, 6-H), 3.96
(ddd, J ) 9.9, 3.6, 2.4 Hz, 9-H), 4.04 (dd, J ) 5.6, 2.7 Hz, 7-H);
13C NMR (100 MHz, CDCl3) 14.0 (C-1 and C-15), 22.6 (C-2 and
C-14), 25.7, 25.9, 28.8, 31.7, 32.0, 34.4 (C-3, C-4, C-5, C-11,
C-12 and C-13), 38.8 (C-8), 71.6 (C-7), 74.0 (C-10), 79.0 (C-9),
84.4 (C-6) ppm; EIMS (70 eV, m/z, %) 258 (M+, 1), 240 (1), 201
(2), 187 (4), 169 (3), 157 (84), 139 (28), 121 (20), 114 (221), 113
(69), 99 (100), 95 (47), 83 (43); HRMS found 258.2188 (C15H30O3
(M+) requires 258.2195).
(E)-2-Octen -1-ol (15). The propargylic alcohol 3 (1.4 g, 11
mmol) in THF (5 mL) was added dropwise over 15 min to an
anhydrous suspension of lithium aluminum hydride (640 mg,
17 mmol) in THF (20 mL) at 0 °C. The resulting suspension
was warmed to 67 °C and stirred for 24 h after which the
reaction mixture was cooled to room temperature and excess
LiAlH4 destroyed by careful addition of dilute aqueous HCl (2
M)(CAUTION!). The resulting solution was then extracted
into Et2O (100 mL), and the organic phase washed with dilute
aqueous HCl (50 mL, 2 M), H2O (2 × 50 mL), and brine (100
mL) and then dried over anhydrous MgSO4 and concentrated
in vacuo to return a yellow oil that was purified by MPLC
(silica, 40% EtOAc/hexane) to yield 15 (1.2 g, 85%) as a
1
colorless mobile oil: IR (film) νmax 3385, 1598 cm-1; H NMR
(400 MHz, CDCl3) δ 0.87 (t, J ) 7.1 Hz, 8-H3), 1.2-1.4 (bm, J
) 5, 6, 7-H2), 1.78 (bs, OH), 2.03 (dt, J ) 7.1, 6.8 Hz, 4-H2),
4.08 (bd, J ) 6.3 Hz, 1-H2), 5.66 (bm, 2 and 3-H); 13C NMR
(100 MHz, CDCl3) 14.0 (C-8), 22.5 (C-7), 28.8 (C-5), 31.3 (C-
6), 32.1 (C-4), 63.7 (C-1), 128.8 (C-2), 133.4 (C-3) ppm; EIMS
(70 eV, m/z, %) 128 (M+, 2), 110 (9), 97 (4), 83 (4), 57 (8), 56
(100).
(E)-1-Ch lor o-2-octen e (16). To a stirred solution of 15
(800 mg, 6.25 mmol) in Et2O/HMPA (3:1, 20 mL) under a
nitrogen atmosphere at 0 °C was added n-BuLi (2.6 mL as a
2.4 M solution in hexane, 0.25 mmol). Addition made the
initally colorless solution turn a deep orange/red color which
dissipated upon addition of p-toluenesulfonyl chloride (1.2 g,
6.3 mmol). The reaction mixture was stirred for 15 min and
then LiCl (700 mg, 21.3 mmol) added and stirring maintained
at room temperature for 10 h after which the reaction mixture
was diluted with Et2O (30 mL), washed with dilute aqueous
HCl (30 mL, 2 M) and H2O (3 × 30 mL), and the organic phase
dried over anhydrous MgSO4 and concentrated in vacuo to
return a yellow oil that was purified by MPLC (silica, 20%
EtOAc/hexane) to yield 16 (690 mg, 76%) as a volatile colorless
oil: IR (film) νmax 1666 cm-1; 1H NMR (400 MHz, CDCl3) δ 0.89
(t, J ) 7.0 Hz, 8-H3), 1.2-1.4 (bm, 5, 6, 7-H2), 2.05 (dt, J )
6.8, 6.6 Hz, 4-H2), 4.03 (dd, J ) 7.1, 1.0 Hz, 1-H2), 5.60 (dtt, J
) 15.1, 7.1, 1.5 Hz, 2-H), 5.75 (dtt, J ) 15.1, 6.6, 1.0 Hz, 3-H);
13C NMR (100 MHz, CDCl3) 14.0 (C-8), 22.5 (C-7), 28.5 (C-5),
31.3 (C-4), 32.0 (C-6), 45.6 (C-1), 125.8 (C-2), 136.3 (C-3) ppm.
(E)-6-P en ta d ecen -9-yn e (17). To a suspension of 1-hep-
tyne (73 mg, 0.76 mmol), K2CO3 (145 mg, 1.1 mmol), TBAC
(19 mg, 0.07 mmol), and CuI (6.7 mg, 0.035 mmol) in DMF (2
mL) under a nitrogen atmosphere was added 16 (100 mg, 0.7
mmol), and the resulting mixture stirred at 40 °C for 12 h.
The reaction was then diluted with Et2O (80 mL) and washed
with H2O (3 × 50 mL), brine (50 mL), and H2O (50 mL), before
the organic phase was dried over anhydrous MgSO4 and then
concentrated in vacuo to return a mobile oil that was purified
by HPLC (silica, hexane) to yield 17 (115 mg, 79%) as a
1
colorless mobile oil: IR (film) νmax 2360, 2341, 1639 cm-1; H
NMR (400 MHz, CDCl3) δ 0.88 and 0.89 (2t, J ) 7.1 Hz, 1 and
15-H3), 1.2-1.4 (bm, 2, 3, 4, 13, 14-H2), 1.49 (m, 12-H2), 2.01

82 J . Org. Chem., Vol. 63, No. 1, 1998
Capon and Barrow
(C-6), 56.0 (C-7), 56.9 (C-10), 58.8 (C-9) ppm; EIMS (70 eV,
m/z, %) 183 (M+ - C4H9, 1), 169 (1), 156 (2), 140 (2), 127 (1),
113 (4), 111 (6), 96 (32), 84 (59), 69 (79), 54 (100); HRMS found
183.1385 (C11H19O2 requires 183.1386), 54.0469 (C4H6 requires
54.0469).
to yield the trans tetrahydrofuran 24 (4.5 mg, 100%) as a
colorless amorphous solid: mp 93-95°; IR (film) νmax 3355
cm-1; 1H NMR (400 MHz, CDCl3) δ 0.88 and 0.89 (2t, J ) 6.6
Hz, 1 and 15-H3), 1.3-1.6 (bm, 2, 3, 4, 5, 11, 12, 13, 14-H2),
1.85 (dd, J ) 13.2, 6.1 Hz, 8-HA), 2.12 (ddd, J ) 13.2, 10.2, 4.4
Hz, 8-HB), 3.84 (dt, J ) 2.9, 6.8 Hz, 6-H), 3.86 (m, 10-H), 4.17
(ddd, J ) 10.2, 6.1, 3.4 Hz, 9-H), 4.29 (dd, J ) 4.4, 2.9 Hz,
7-H); 13C NMR (100 MHz, CDCl3) 14.0 (C-1 and C-15), 22.6,
22.6 (C-2 and C-14), 26.0, 26.0, 29.2, 31.8, 32.0, 32.2 (C-3, C-4,
C-5, C-11, C-12, and C-13), 34.2 (C-8), 72.1 (C-10), 73.3 (C-7),
80.0 (C-9), 83.6 (C-6) ppm; EIMS (70 eV, m/z, %) 258 (M+, 1),
240 (1), 214 (1), 201 (1), 187 (1), 169 (1), 157 (78), 139 (29),
121 (20), 114 (21), 113 (100), 101 (15), 96 (18), 95 (69), 83 (31),
69 (39), 57 (33), 56 (44), 54 (72); HRMS found 258.2195
(C15H30O3 requires 258.2193).
(6S*,7S*,9S*,10R*)-6,9-Epoxypen tadecan e-7,10-diol (25).
A solution of 23 (4.9 mg, 0.016 mmol) in MeOH (3 mL) and
NH4OH (33% aq solution, 1 mL) was stirred at room temper-
ature for 5 h after which it was concentrated in vacuo to yield
the cis tetrahydrofuran 25 (4.2 mg, 100%) as a colorless oil:
IR (film) νmax 3355 cm-1; 1H NMR (400 MHz, CDCl3) δ 0.89 (t,
J ) 6.7 Hz, 1 and 15-H3), 1.3-1.65 (bm, 2, 3, 4, 5, 11, 12, 13,
14-H2), 1.91 (ddd, J ) 14.2, 3.4, 1.7 Hz, 8-HA), 2.19 (ddd, J )
14.2, 10.0, 5.4 Hz, 8-HB), 3.59 (dt, J ) 2.7, 6.8 Hz, 6-H), 3.84
(ddd, J ) 7.4, 5.1, 2.2 Hz, 10-H), 4.00 (ddd, J ) 10.0, 3.4, 2.2
Hz, 9-H), 4.03 (ddd, J ) 5.4, 2.7, 1.7 Hz, 7-H); 13C NMR (100
MHz, CDCl3) 14.0, 14.0 (C-1 and C-15), 22.5, 22.6 (C-2 and
C-14), 25.6, 26.0, 28.8, 31.7, 32.1, 33.3 (C-3, C-4, C-5, C-11,
C-12 and C-13), 34.3 (C-8), 71.2 (C-7), 72.1 (C-10), 79.9 (C-9),
83.9 (C-6) ppm; EIMS (70 eV, m/z, %) 258 (M+, 2), 240 (1), 214
(1), 201 (3), 187 (2), 169 (2), 157 (93), 140 (17), 139 (44), 121
(21), 114 (36), 113 (100), 101 (29), 96 (30), 95 (67), 84 (21), 83
(47), 69 (45), 57 (51), 56 (49), 54 (83); HRMS found 258.2199
(C15H30O3 requires 258.2195).
(6R*,7R*,9R*,10S*)-6,7:9,10-Bis(epoxy)pen tadecan e (21):
1H NMR (400 MHz, CDCl3) δ 0.89 and 0.90 (2t, J ) 7.1 Hz, 1
and 15-H3), 1.25-1.6 (bm, 2, 3, 4, 5, 11, 12, 13, 14-H2), 1.81
(d, J ) 5.1 Hz, 8-HA), 1.83 (dd, J ) 5.1, 1.2 Hz, 8-HB), 2.82 (dt,
J ) 2.2, 5.4 Hz, 6-H), 2.85 (ddd, J ) 5.1, 5.1, 2.2 Hz, 7-H),
2.94 (dt, J ) 4.2, 5.9 Hz, 10-H), 3.10 (ddd, J ) 6.1, 5.9, 4.2 Hz,
9-H); 13C NMR (100 MHz, CDCl3) 14.0 (C-1 and C-15), 22.6
(C-2 and C-14), 25.7, 26.2, 27.9, 31.6, 31.7, 31.9 (C-3, C-4, C-5,
C-11, C-12 and C-13), 30.4 (C-8), 53.3 (C-9), 55.8 (C-7), 56.5
(C-10), 58.2 (C-6) ppm; EIMS (70 eV, m/z, %) 183 (M+ - C4H9,
1), 169 (1), 157 (1), 140 (4), 139 (9), 127 (7), 113 (19), 111 (7),
96 (27), 84 (41), 69 (65), 54 (100). HRMS found 183.1385
(C11H19O2 requires 183.1386).
Cycliza tion of (6R*,7R*,9S*,10R*)-6,7:9,10-Bis(ep oxy)-
p en ta d eca n e (20). The bisepoxide 20 (10 mg, 0.042 mmol)
in glacial acetic acid (2 mL) was stirred at 100 °C for 24 h
after which the solution was cooled to room temperature and
diluted with Et2O (30 mL) and the organic phase washed with
H2O (3 × 30 mL), saturated NaHCO3 solution (30 mL), and
H2O (20 mL). The organic phase was dried over anhydrous
MgSO4 and concentrated in vacuo to return a pale yellow oil
(12 mg) which was purified by HPLC (silica, 40% EtOAc/
hexane) to yield the trans tetrahydrofuran acetate 22 (8.8 mg,
70%) and the cis tetrahydrofuran acetate 23 (2.5 mg, 20%) as
colorless oils: (6R*,7R*,9S*,10R*)-6,9-ep oxyp en ta d eca n e-
1
7,10-d iol 7-a ceta te (22): IR (film) νmax 3465, 1740 cm-1; H
NMR (400 MHz, CDCl3) δ 0.88 and 0.89 (2t, J ) 6.8 Hz, 1 and
15-H3), 1.25-1.6 (bm, 2, 3, 4, 5, 11, 12, 13, 14-H2), 1.88 (ddd,
J ) 13.7, 6.1, 1.0 Hz, 8-HA), 2.09 (s, COCH3), 2.20 (ddd, J )
13.7, 10.0, 4.6 Hz, 8-HB), 3.85 (dt, J ) 3.6, 6.9 Hz, 10-H), 3.97
(ddd, J ) 7.6, 5.9, 3.6 Hz, 6-H), 4.10 (ddd, J ) 10.0, 6.1, 3.6
Hz, 9-H), 5.34 (bdd, J ) 4.6, 3.6 Hz, 7-H); 13C NMR (100 MHz,
CDCl3) 14.0, 14.0 (C-1 and C-15), 21.1 (COCH3), 22.5, 22.5 (C-2
and C-14), 25.6, 25.9, 29.4, 31.8, 31.9, 32.2 (C-3, C-4, C-5, C-11,
C-12, and C-13), 32.0 (C-8), 71.8 (C-10), 75.4 (C-7), 80.3 (C-9),
82.1 (C-10), 170.5 (COCH3) ppm; EIMS (70 eV, m/z, %) 240
(M+ - HOAc, 1), 199 (M+ - C6H13O, 8), 140 (18), 139 (100),
113 (4), 95 (6), 84 (7), 69 (7), 67 (4), 54 (15); HRMS found
10-Ep im er (26) of th e Na tu r a l Dih yd r oxytetr a h yd r o-
fu r a n 1. To a solution of the natural product 1 (87 mg, 0.28
mmol) in CH2Cl2 (5 mL) was added pyridinium dichromate
(160 mg, 0.42 mmol) and the reaction mixture stirred at room
temperature for 48 h, after which it was filtered through a
plug of Celite and the filtrate concentrated in vacuo to return
a crude mixture of products that were resolved by HPLC
(silica, 30% EtOAc/hexane) to yield, in decreasing order of
polarity, (6S,7S,9R)-7-h yd r oxy-6,9-ep oxyn on a d ec-18-en -
10-on e (29 mg, 33%): an unstable colorless oil; [R]D +20.4 (c
199.1334 (C11H19O3 requires 199.1332), 139.1123 (C9H15
requires 139.1123).
O
1
) 1.0, CHCl3); IR (film) νmax 3445, 1715, 1640 cm-1; H NMR
(6S*,7S*,9S*,10R*)-6,9-Epoxypen tadecan e-7,10-diol 7-ac-
eta te (23): IR (film) νmax 3468, 1739 cm-1; 1H NMR (400 MHz,
CDCl3) δ 0.88 (t, J ) 6.8 Hz, 1 and 15-H3), 1.3-1.6 (bm, 2, 3,
4, 5, 11, 12, 13, 14-H2), 1.95 (ddd, J ) 14.4, 6.3, 1.7 Hz, 8-HA),
2.06 (s, COCH3), 2.23 (ddd, J ) 14.4, 8.1, 6.6 Hz, 8-HB), 3.79
(ddd, J ) 7.7, 5.7, 3.7 Hz, 6-H), 3.86 (bm, 10-H and 9-H), 5.21
(ddd, J ) 6.6, 3.7, 1.7 Hz, 7-H); 13C NMR (100 MHz, CDCl3)
14.0, 14.0 (C-1 and C-15), 21.1 (COCH3), 22.5, 22.6 (C-2 and
C-14), 25.5, 25.9, 28.5, 31.8, 31.9, 32.6 (C-3, C-4, C-5, C-11,
C-12, and C-13), 32.2 (C-8), 71.0 (C-10), 74.5 (C-7), 80.4 (C-9),
81.7 (C-6), 170.6 (COCH3) ppm; EIMS (70 eV, m/z, %) 199 (M+
- C6H13O, 5), 175 (2), 140 (26), 139 (100), 113 (3), 91 (23), 84
(13), 69 (10), 54 (21); HRMS found 199.1334 (C11H19O3 requires
199.1332), 139.1121 (C9H15O requires 139.1123).
Cycliza tion of (6R*,7R*,9R*,10S*)-6,7:9,10-Bis(ep oxy)-
p en ta d eca n e (21). The bisepoxide 21 (10 mg, 0.042 mmol)
in glacial acetic acid (2 mL) was stirred at 100 °C for 24 h
after which the solution was cooled to room temperature and
diluted with Et2O (30 mL), and the organic phase was washed
with H2O (3 × 30 mL), saturated NaHCO3 solution (30 mL),
and H2O (20 mL). The organic phase was dried over anhy-
drous MgSO4 and concentrated in vacuo to return a pale yellow
oil (12 mg) which was purified by HPLC (silica, 40% EtOAc/
hexane) to yield the trans tetrahydrofuran acetate 22 (1.9 mg,
19%) and the cis tetrahydrofuran acetate 23 (6.8 mg, 68%) as
colorless oils.
(100 MHz, CDCl3) δ 0.88 (t, J ) 6.8 Hz, 1-H3), 1.2-1.6
(methylene envelope, 2, 3, 4, 5, 12, 13, 14, 15, 16-H2), 2.01 (dt,
J ) 6.8, 6.8 Hz, 17-H2), 2.09 (ddd, J ) 13.7, 8.3, 4.8 Hz, 8-HA),
2.22 (ddd, J ) 13.7, 8.3, 0.7 Hz, 8-HB), 2.48 (dt, J ) 17.6, 7.4
Hz, 11-HA), 2.54 (dt, J ) 17.6, 7.4 Hz, 11-HB), 3.75 (dt, J )
2.9, 7.0 Hz, 6-H), 4.22 (dd, J ) 4.8, 2.9 Hz, 7-H), 4.55 (dd, J )
8.3, 8.3 Hz, 9-H), 4.93 (ddt, J ) 10.3, 2.2, 1.3 Hz, 19-Hcis), 4.99
(ddt, J ) 17.1, 2.2, 1.5 Hz, 19-Htrans), 5.80 (ddt, J ) 17.1, 10.3,
6.8 Hz, 18-H); 13C NMR (100 MHz, CDCl3) δ 14.0 (C-1), 22.5
(C-2), 23.2 (C-4), 25.9 (C-12), 28.6, 28.8, 28.9, 29.1, 29.2, 29.2
(C-5, C-11, C-13, C-14 and C-16), 31.9 (C-3), 33.7 (C-17), 38.3
(C-8), 72.5 (C-7), 81.0 (C-6), 84.1 (C-9), 114.2 (C-19), 139.1 (C-
18), 212.5 (C-10) ppm; EIMS (70 eV, m/z, %) 310 (M+, 2), 157
(100), 139 (17), 121 (14), 113 (60), 95 (42), 69 (33), 55 (38), 43
(34); HRMS found 310.2508 (C19H34O3 requires 310.2507).
(6S,9R,10R)-10-h ydr oxy-6,9-epoxyn on adec-18-en -7-on e (14
mg, 16%): a stable colorless oil; [R]D +33.2 (c ) 1.0, CHCl3);
IR (film) νmax 3460, 1755, 1640 cm-1 1H NMR (400 MHz,
;
CDCl3) δ 0.88 (t, J ) 6.8 Hz, 1-H3), 1.2-1.6 (methylene
envelope, 2, 3, 4, 5, 11, 12, 13, 14, 15, 16-H2), 2.03 (dt, J ) 6.8,
6.8 Hz, 17-H2), 2.25 (bs, OH), 2.42 (ddd, J )18.3, 7.1, 0.9 Hz,
8-HA), 2.52 (dd, J ) 18.3, 7.1 Hz, 8-HB), 3.54 (bm, 10-H), 3.98
(dd, J ) 8.1, 4.6 Hz, 6-H), 4.18 (ddd, J ) 7.1, 7.1, 5.4 Hz, 9-H),
4.92 (ddt, J ) 10.3, 2.2, 1.2 Hz, 19-Hcis), 4.99 (ddt, J ) 17.1,
2.2, 1.5 Hz, 19-Htrans), 5.81 (ddt, J )17.1, 10.3, 6.8 Hz, 18-H);
13C NMR (100 MHz, CDCl3) δ 14.0 (C-1), 22.4 (C-2), 24.9 (C-
4), 25.5 (C-12), 28.9, 29.0, 29.3, 29.5 (C-13, C-14, C-15 and
C-16), 31.0 (C-5), 31.5 (C-3), 33.2 (C-11), 33.8 (C-17), 38.9 (C-
8), 73.6 (C-10), 77.8 (C-6), 79.8 (C-9), 114.1 (C-19), 139.1 (C-
18), 215.8 (C-7) ppm; EIMS (70 eV, m/z, %) 310 (M+, 24), 240
(6R*,7R*,9S*,10R*)-6,9-Epoxypen tadecan e-7,10-diol (24).
A solution of 22 (5.2 mg, 0.017 mmol) in MeOH (2 mL) and
NH4OH (33% aq solution, 0.5 mL) was stirred at room
temperature for 5 h after which it was concentrated in vacuo

A Biomimetic Transformation
J . Org. Chem., Vol. 63, No. 1, 1998 83
(2), 157 (20), 156 (18), 155 (12), 128 (16), 127 (17), 101 (30), 99
(78), 57 (100); HRMS found 310.2507 (C19H34O3 requires
310.2508). (6S,9R)-6,9-epoxyn on adec-18-en e-7,10-dion e (42
mg, 48%): a moderately stable colorless oil; [R]D -35.9 (c )
1.0, CHCl3); IR (film) νmax 1760, 1720 cm-1; 1H NMR (400 MHz,
CDCl3) δ 0.88 (t, J ) 6.8 Hz, 1-H3), 1.3-1.7 (methylene
envelope, 2, 3, 4, 5, 12, 13, 14, 15, 16-H2), 2.04 (dt, J ) 6.8, 6.8
Hz, 17-H2), 2.60 (t, J ) 7.4 Hz, 11-H2), 2.62 (dd, J ) 18.3, 8.8
Hz, 8-HA), 2.72 (dd, J ) 18.3, 5.4 Hz, 8-HB), 3.90 (dd, J ) 7.8,
4.5 Hz, 6-H), 4.74 (dd, J ) 8.8, 5.4 Hz, 9-H), 4.92 (ddt, J )
10.3, 2.2, 1.2 Hz, 19-Hcis), 4.99 (ddt, J ) 17.1, 2.2, 1.5 Hz, 19-
Htrans), 5.81 (ddt, J ) 17.1, 10.3, 6.8 Hz, 18-H); 13C NMR (100
MHz, CDCl3) δ 14.0 (C-1), 22.4 (C-2), 23.1 (C-4), 24.8 (C-12),
28.8, 28.9, 29.1, 29.2, 30.8 (C-5, C-13, C-14, C-15, and C-16),
31.3 (C-3), 33.7 (C-17), 37.5 (C-11), 38.7 (C-8), 78.7 (C-6), 79.7
(C-9), 114.2 (C-19), 139.1 (C-18), 209.7 (C-10), 213.7 (C-7) ppm;
EIMS (70 eV, m/z, %) 308 (M+, 2), 266 (2), 237 (1), 209 (8),
181 (29), 151 (52), 135 (39), 127 (71), 111 (47), 99 (23), 83 (81),
69 (57), 55 (100), 43 (40), 41 (63); HRMS found 308.2351
(C19H32O3 requires: 308.2351).
(6S,7S,9R,10S)-6,9-Ep oxyn on a d ec-18-en e-7,10-d iol (26).
A sample of (6S,7S,90R)-7-hydroxy-6,9-epoxynonadec-18-en-
10-one (25 mg, 0.08 mmol) in MeOH (10 mL) was treated with
NaBH4 (60 mg, excess) and the mixture stirred at room
temperature for 2 h, after which it was concentrated in vacuo
to return a colorless waxy solid which was extracted into Et2O
(30 mL). The ethereal extract was washed with H2O (30 mL),
saturated NaHCO3 solution (20 mL), and dilute aqueous HCl
(20 mL, 2M), dried over anhydrous MgSO4, filtered, and
concentrated in vacuo to yield a waxy solid (24.5 mg, 97%) that
was resolved by HPLC (silica, 40% EtOAc/hexane) into a 1.2:1
ratio of the natural dihydroxy tetrahydrofuran 1 and the 10-
epimer 26: a stable colorless crystalline solid; mp 98-99 °C
(from hexane); [R]D +9.2° (c ) 0.25, CHCl3); IR (film) νmax 3375,
3325, 1640 cm-1; 1H NMR (400 MHz, CDCl3) δ 0.89 (t, J ) 6.8
Hz, 1-H3), 1.3-1.6 (methylene envelope, 2, 3, 4, 5, 11, 12, 13,
14, 15, 16-H2), 1.85 (bdd, J ) 13.2, 6.1 Hz, 8-HA), 1.96 (bs,
OH), 2.03 (bdt, J ) 6.8, 7.1 Hz, 17-H2), 2.12 (ddd, J ) 13.2,
10.3, 4.4 Hz, 8-HB), 3.84 (dt, J ) 2.9, 7.1 Hz, 6-H), 3.86 (m,
10-H), 4.16 (ddd, J ) 10.3, 6.1, 3.5 Hz, 9-H), 4.29 (bs, 7-H),
4.94 (ddt, J ) 10.1, 2.2, 1.2 Hz, 19-Hcis), 4.99 (ddt, J ) 17.1,
2.2, 1.5 Hz, 19-Htrans), 5.81 (ddt, J ) 17.1, 10.1, 6.8 Hz, 18-H);
13C NMR (100 MHz, CDCl3) δ 14.0 (C-1), 22.6 (C-2), 25.9, 26.0,
28.9, 29.0, 29.2, 29.4, 29.6 (C-4, C-5, C-12, C-13, C-14, C-15
and C-16), 32.0 (C-3), 32.3 (C-11), 33.8 (C-17), 34.3 (C-8), 72.1
(C-10), 73.3 (C-7), 80.1 (C-9), 83.5 (C-6), 114.1 (C-19), 139.2
(C-18) ppm; EIMS (70 eV, m/z, %) 312 (M+, 1), 276 (2), 157
(76), 139 (38), 121 (37), 113 (100), 95 (87), 81 (44), 69 (56), 57
(63), 55 (90); HRMS found 312.2666 (C19H36O3 requires
312.2664).
Bisep oxid es 28 a n d 29 of tr a n s,tr a n s-Meth yl Lin olea te
(27). To a solution of trans,trans-methyl linoleate (50 mg, 0.17
mmol) in CH2Cl2 (10 mL) was added m-CPBA (73 mg, 0.42
mmol) and the reaction stirred at room temperature for 18 h,
after which the reaction mixture was added to H2O (30 mL)
and extracted with Et2O (3 × 30 mL). The combined ethereal
extract was washed with NaOH (2 M, 3 × 15 mL) and H2O
(30 mL) and then dried over anhydrous MgSO4, filtered, and
concentrated in vacuo to return a light yellow oil (60 mg,
100%). This material proved to be an inseparable mixture of
stereoisomeric bisepoxides for which NMR analysis revealed
both syn and anti diastereomers.
Cycliza tion of Bisep oxid es 28 a n d 29. A solution of 28
and 29 (60 mg, 0.2 mmol) in glacial acetic acid (5 mL) was
stirred at 100 °C for 24 h, after which the reaction mixture
was added to H2O (30 mL) and extracted with Et2O (3 × 30
mL). The combined ethereal extract was washed with NaOH
(2 M, 3 × 15 mL) and H2O (30 mL) and then dried over
anhydrous MgSO4, filtered, and concentrated in vacuo to
return a light yellow oil (40 mg). NMR analysis revealed no
trace of resonances consistent with either the starting material
or cyclized products, but instead was dominated by multiple
acetate resonances suggestive of a mixture of acyclic diol
diacetate isomers.
Ack n ow led gm en t. The assistance of J . Page in
investigating the acid-catalyzed cyclization of tran-
s,trans bisepoxides is gratefully acknowledged. We
would also like to acknowledge the role of T. Friedel,
D. Wadsworth and E. Lacey in codiscovering the an-
thelmintic properties of epoxylipids from N. anomala.8
This research was funded by the Australian Research
Council.
Su p p or tin g In for m a tion Ava ila ble: Figures showing 13
C
NMR spectra for 3-26, 1H NMR for 9, 12, and 26, and
HETCOR data for 9 and 12 are provided (30 pages). This
material is contained in libraries on microfiche, immediately
follows this article in the microfilm version of the journal, and
can be ordered from the ACS; see any current masthead page
for ordering information.
J O971147K