An Olefin Metathesis Approach to 36- And 72-Membered Archaeal Macrocyclic Membrane Lipids

Article abstract of DOI:10.1021/jo980472k

An olefin metathesis approach, which has been successfully applied to an efficient synthesis of archaeal 36- and 72-membered macrocyclic membrane lipids (1, 2a, and 2b), is reported. In the presence of a Grubbs' ruthenium-alkylidene complex, RuCl₂

Full text of DOI:10.1021/jo980472k

J . Org. Chem. 1998, 63, 4741-4745
4741
An Olefin Meta th esis Ap p r oa ch to 36- a n d 72-Mem ber ed Ar ch a ea l
Ma cr ocyclic Mem br a n e Lip id s
Kenji Arakawa, Tadashi Eguchi, and Katsumi Kakinuma*
Department of Chemistry, Tokyo Institute of Technology, O-okayama, Meguro-ku, Tokyo 152-8551, J apan
Received March 12, 1998
An olefin metathesis approach, which has been successfully applied to an efficient synthesis of
archaeal 36- and 72-membered macrocyclic membrane lipids (1, 2a , and 2b), is reported. In the
presence of a Grubbs’ ruthenium-alkylidene complex, RuCl2(dCHPh)(PCy3)2 (3), a ring-closing
metathesis (RCM) reaction of R,ω-diene 5 efficiently proceeded in 79% yield under high dilution
conditions to give 36-membered 6. By changing the reaction conditions, a acyclic diene metathesis
(ADM) product 7 was predominantly formed from the same substrate 5. The acyclic product 7
was subsequently subjected to the RCM reaction under high dilution conditions to provide 72-
membered compound 8 in 45% yield. Final catalytic hydrogenation of 6 and 8 afforded the 36-
membered lipid 1 and a mixture of the 72-membered lipid 2a and 2b, respectively. The present
synthetic method appears to be of significant advantage for the synthesis of such giant ring
structures of the 36- and 72-membered lipids, because both of the macrocylic lipids can be obtained
in a short step at will from the same starting material only by changing the order and conditions
of the metathesis reaction.
In tr od u ction
archaea are the unique chemical structures of the
membrane core lipids, that is, glycerol is linked to
isoprenoid chains with ethereal bonding, in contrast to
ester linkage with fatty acids in the bacterial and
eukaryotic membrane lipids.6 The most striking feature
of the archaeal membrane lipids is found in the presence
of macrocyclic structures as large as 36- and 72-
membered rings (1 and 2a b), as shown in Figure 1.6 The
former was discovered from a methanogen Methanococ-
cus jannaschii isolated from a deep-sea hydrothermal
vent and the latter being found in methanogenic and
thermophilic archaea such as Methanobacterium ther-
moautotrophicum, Thermoplasma, and Sulfolobus.5 In
addition, Arigoni et al. recently reported that the 72-
membered lipids exist as a mixture of regioisomers in
terms of the glycerol arrangements such as 2a and 2b.7
These unusual lipids have attracted attention in connec-
tion with their physicochemical properties, including high
stability under extreme conditions. Modeling and syn-
thetic studies of the archaeal membrane lipids have so
far been reported in order to shed light on the stability,
Transition metal catalyzed carbon-carbon bond for-
mation is an important reaction in organic synthesis.
Among such transition metal-catalyzed reactions is olefin
metathesis, which involves the exchange reaction of
alkylidene moieties between two alkenes.1 While the
metathesis reaction has long been used in polymer
chemistry, recently developed homogeneous catalysts,
such as the molybdenum-alkylidene complexes intro-
duced by Schrock et al.2 as well as the ruthenium-
alkylidene complexes of Grubbs et al.,3 facilitated sig-
nificant improvement of the olefin metathesis as a useful
synthetic method. Especially, ring-closing metathesis
(RCM) with these catalysts provides an efficient and
widely applicable way for constructing varieties of ring
sizes, and as a result, the RCM methodology has increas-
ingly been used for natural product synthesis.4
Archaea (archaebacteria) have been attracting wide
attention from biochemical and evolutionary viewpoints.
It has now been established that the archaea are distinct
from bacteria and eukarya and are classified in the third
independent domain.5 Among the major interests in
(4) For examples of the ring-closing metathesis methodology of
natural product synthesis, see: (a) Fu¨rstner, A.; Langemann, K. J .
Org. Chem. 1996, 61, 3942. (b) Fu¨rstner, A.; Langemann, K. J . Org.
Chem. 1996, 61, 8746. (c) Nicolaou, K. C.; He, Y.; Vourloumis, D.;
Vallberg, H.; Roschangar, F.; Sarabia, F.; Ninkovic, S.; Yang, Z.;
Trujillo, J . I. J . Am. Chem. Soc. 1997, 119, 7960. (d) Fu¨rstner, A.;
Langemann, K. J . Am. Chem. Soc. 1997, 119, 9130. (e) Meng, D.;
Bertinato, P.; Balog, A.; Su, D.-S.; Kamenecka, T.; Sorensen, E. J .;
Danishefsky, S. J . J . Am. Chem. Soc. 1997, 119, 10073. (f) Xu, Z.;
J ohannes, C. W.; Houri, A. F.; La, D. S.; Cogan, D. A.; Hofilena, G. E.;
Hoveyda, A. H. J . Am. Chem. Soc. 1997, 119, 10302. (g) Fu¨rstner, A.;
Mu¨ller, T. J . Org. Chem. 1998, 63, 424.
(5) (a) Woese, C. R.; Fox, G. E. Proc. Natl. Acad. Sci. U.S.A. 1977,
74, 5088. (b) Woese, C. R.; Kandler, O.; Wheelis, M. L. Proc. Natl. Acad.
Sci. U.S.A. 1990, 87, 4576.
(6) (a) Kates, M. The Biochemistry of Archaea (Archaebacteria);
Kates, M., Kushner, D. J ., Matheson, A. T., Eds.; Elsevier: Amsterdam,
1993; p 261. (b) Gambacorta, A.; Gliozzi, A.; De Rosa, M. World J .
Microbiol. Biotechnol. 1995, 11, 115.
* Fax: +81-3-5734-3713. E-mail: kakinuma@chem.titech.ac.jp.
(1) For reviews: see (a) Schuster, M.; Blechert, S. Angew. Chem.,
Int. Ed. Engl. 1997, 36, 2036-2056. (b) Grubbs, R. H. Alkene Metath-
esis and Related Reactions; Comprehensive Organic Synthesis; Per-
gamon Press: Oxford, 1991; Vol 5, p 1115.
(2) (a) Schaverien, C. J .; Dewan, J . C.; Schrock, R. R. J . Am. Chem.
Soc. 1986, 108, 2771. (b) Schrock, R. R.; Feldman, J .; Cannitzo, L. F.;
Grubbs, R. H. Macromolecules 1987, 20, 1172. (c) Schrock, R. R.;
Krouse, S. A.; Knoll, K.; Feldman, J .; Murdzek, J . S.; Yang, D. C. J .
Mol. Catal. 1988, 46, 243. (d) Schrock, R. R.; DePue, R. T.; Feldman,
J .; Schaverien, C. J .; Dewan, J . C.; Liu, A. H. J . Am. Chem. Soc. 1988,
110, 1423. (e) Schrock, R. R. Acc. Chem. Res. 1990, 23, 158. (f) Schrock,
R. R.; Murdzek, J . S.; Bazan, G. C.; Robbins, J .; DiMare, M.; O′Regan,
M. J . Am. Chem. Soc. 1990, 112, 3875.
(3) (a) Grubbs, R. H.; Miller, S. J .; Fu, G. C. Acc. Chem. Res. 1995,
28, 446. (b) Schwab, P.; Grubbs, R. H.; Ziller, J . W. J . Am. Chem. Soc.
1996, 118, 100. (c) Dias, E. L.; Nguyen, S. T.; Grubbs, R. H. J . Am.
Chem. Soc. 1997, 119, 3887. (d) Schneider, M. F.; Lucas, N.; Velder,
J .; Blechert, S. Angew. Chem., Int. Ed. Engl. 1997, 36, 257.
(7) Gra¨ther, O.; Arigoni, D. J . Chem. Soc., Chem. Commun. 1995,
405.
S0022-3263(98)00472-1 CCC: $15.00 © 1998 American Chemical Society
Published on Web 06/11/1998

4742 J . Org. Chem., Vol. 63, No. 14, 1998
Arakawa et al.
F igu r e 1. Core structures of archaeal macrocyclic membrane lipids (1, 2a , and 2b).
F igu r e 2. The concept of the metathesis approach toward the archaeal macrocyclic lipids.
fluidity, and permeability.8 However, little is known of
such a large ring as 36- and 72-membered macrocyclic
lipids.
new approach involving olefin metathesis toward the
archaeal 36- and 72-membered macrocyclic lipids (1, 2a ,
and 2b).
Concerning the synthetic efforts toward such macro-
cyclic lipids of natural form, we recently reported the first
total syntheses of the macrocyclic 36-membered lipid 1
and 72-membered lipids 2a and 2b, where the McMurry
coupling reaction9 was a key step of macrocyclic ring
formation.10 In this paper, we wish to describe another
Resu lts a n d Discu ssion
The concept of our new approach toward the archaeal
macrocyclic lipids employing olefin metathesis is outlined
in Figure 2. Although an intramolecular metathesis
reaction usually competes with an intermolecular reac-
tion, the 36-membered lipid can conceivably be available
from R,ω-diene by RCM under high dilution conditions
through the first catalytic cycle. In contrast, acyclic diene
metathesis (ADM) may predominantly proceed to afford
an intermediary triene derivative as the concentration
of R,ω-diene is increased. It should be pointed out,
therefore, that the second RCM reaction can be facilitated
by changing the reaction conditions after the ADM
reaction, as shown in the second cycle to give rise to
(8) (a) Lazrak, T.; Milon, A.; Wolff, G.; Albrecht, A.-M.; Miehe´, M.;
Ourisson, G.; Nakatani, Y. Biochim. Biophys. Acta 1987, 903, 132. (b)
Yamauchi, K.; Sakamoto, Y.; Moriya, A.; Yamada, K.; Hosokawa, T.;
Higuchi, T.; Kinoshita, M. J . Am. Chem. Soc. 1990, 112, 3188. (c)
Yamauchi, K.; Yamada, K.; Kinoshita, M.; Kamikawa, T. Bull. Chem.
Soc. J pn. 1991, 64, 2088. (d) Thompson, D. H.; Wong, K. F.; Humphry-
Baker, R.; Wheeler, J . J .; Kim, J .-M.; Rananavare, S. B. J . Am. Chem.
Soc. 1992, 114, 9035. (e) Kim, J .-M.; Thompson, D. H. Langmuir 1992,
8, 637. (f) Moss, R. A.; Li, J .-M. J . Am. Chem. Soc. 1992, 114, 9227. (g)
Yamauchi, K.; Doi, K.; Kinoshita, M.; Kii, F.; Fukuda, H. Biochim.
Biophys. Acta 1992, 1110, 171. (h) He´bert, N.; Beck, A.; Lennox, R. B.;
J ust, G. J . Org. Chem. 1992, 57, 1777. (i) Menger, F. M.; Chen, X. Y.;
Brocchini, S.; Hopkins, H. P.; Hamilton, D. J . Am. Chem. Soc. 1993,
115, 6600. (j) Ladika, M.; Fisk, T. E.; Wu, W. W.; J ons, S. D. J . Am.
Chem. Soc. 1994, 116, 12093. (k) Menger, F. M.; Chen, X. Y.
Tetrahedron Lett. 1996, 37, 323.
(10) (a) Eguchi, T.; Terachi, T.; Kakinuma, K. Tetrahedron Lett.
1993, 34, 2175. (b) Eguchi, T.; Arakawa, K.; Terachi, T.; Kakinuma,
K. J . Org. Chem. 1997, 62, 1924. (c) Eguchi, T.; Kano, H.; Arakawa,
K.; Kakinuma, K. Bull. Chem. Soc. J pn. 1997, 70, 2545. (d) Eguchi,
T.; Ibaragi, K.; Kakinuma, K. J . Org. Chem. 1998, 63, 2689.
(9) (a) McMurry, J . E. Chem. Rev. 1989, 89, 1513. (b) McMurry, J .
E.; Rico, J . G. Tetrahedron Lett. 1989, 30, 1169. (c) Fu¨rstner, A.;
Bogdanovic´, B. Angew. Chem., Int. Ed. Engl. 1996, 35, 2442.

An Olefin Metathesis Approach to Membrane Lipids
J . Org. Chem., Vol. 63, No. 14, 1998 4743
Ta ble 1. Resu lts of RCM r ea ction of 5a
Ta ble 2. Resu lts of th e ADM r ea ction of 5a
yield (%)b
substrate
catalyst
entry concn (mM) (mol %)
conditions
rt, 115 h
reflux, 42 h 79 trace
reflux, 36 h 55
reflux, 12 h 15 12
6
7
8
1c
2
5.1
3.8
7.8
10
29
22
20
yield (%)b
6
11
11
substrate
catalyst
recovered
3
6
entry concn (mM) (mol %) conditions
5
7c
4
29
a
1
2
3
4
40
78
108
408
7
20
20
20
rt, 63 h
rt, 22 h
rt, 9 h
60
59
57
43
28 (70)
26 (63)
35 (81)
19 (33)
All reactions were carried out in CH2Cl2 under an Ar atmo-
sphere. Isolated yield. c The starting 5 was quantitatively recov-
ered.
b
rt, 20 h
a
All reactions were carried out in CH2Cl2 under an Ar atmo-
dimerized 72-membered lipids. Thus, this strategy should
allow us to obtain the 36-membered lipid as well as the
72-membered compounds stepwise or in one pot from the
same starting material. Although this reaction sequence
ultimately provides an isomeric mixture of the 72-
membered lipids 2a and 2b, the state of mixture is by
no means problematic. Actually, Arigoni et al. recently
reported that the 72-membered lipids exist as a mixture
of regioisomers in terms of the glycerol arrangements
such as 2a and 2b in several archaea,7 and we have
deduced that the physicochemical as well as polymor-
phismic properties of the synthesized 2a and 2b in pure
form are indistinguishable.10d What is important is,
therefore, the better availability of the chemically defined
72-membered lipids even as a mixture, especially for the
various physicochemical analyses, in order to understand
their behavior.
sphere. b Isolated yield. c Conversion yields (%) of 7 were estimated
by subtracting the recovered 5 and are shown in parentheses.
concentration increased. The possibility of the formation
of 7 and 8 via a ring-opening metathesis13 from 6 was
ruled out, since no reaction was observed when the
isolated 6 was subjected to the same metathesis condi-
tions and the starting 6 was quantitatively recovered.
Therefore, the internal olefin in this case is not reactive
enough for metathesis, probably due to a steric factor.14
The importance of steric effect for the reactivity in
metathesis was previously reported.4a Apparently, the
ADM and the subsequent RCM processes took place.
These observations clearly demonstrated the possibility
of 72-membered ring formation from 5 by the olefin
metathesis approach.
The next was to optimize the reaction conditions for
the ADM reaction starting from 5. As was mentioned
above, the RCM reaction of 5 preferentially proceeded
under high dilution conditions and an increase of the
concentration of 5 led to polymerization under reflux
conditions; however, we observed at the same time that
lowering the reaction temperature to room temperature
diminished the undesired polymerization, even at higher
concentration. To optimize the reaction conditions, we
attempted the ADM reaction of 5 in various substrate
concentrations, and the results are shown in Table 2. In
all cases, the reactions were not completed; however, the
high conversion yield of 81% was observed in entry 3.
The recovered starting material 5 can be recycled after
chromatographic separation. Under these reaction con-
ditions, the RCM product 6 and the tandem ADM-RCM
product 8 were not obtained. Prolonged reaction time
led to a lower yield of the desired 7, probably due to
polymerization.
We first explored the possibility of a RCM reaction
leading to the 36-membered lipid 1. The substrate for
the metathesis reaction, R,ω-diene 5, was prepared from
the known dialdehyde 410b by treatment with Ph3PdCH2
in 95% yield. Among the several olefin metathesis
catalysts tested, a ruthenium-alkylidene complex, RuCl2-
(dCHPh)(PCy3)2 (3), developed by Grubbs et al.,3 was
found to be effective for the metathesis of 5. The results
of the RCM reaction of 5 under various reaction condi-
tions are summarized in Table 1.11
While the RCM reaction of 5 did not occur at room
temperature under high dilution conditions at all (entry
1), the RCM reaction took place by raising the reaction
temperature to reflux to afford the 36-membered com-
pound 6 (entries 2-4). This may be due to facilitation
of the release of highly volatile ethylene. In the case of
entry 2, the RCM product 6 was obtained in yields as
high as 79%.12 The geometry of the newly formed double
bond of 6 was found to be a mixture of approximately
1
7:1 (E/Z), deduced by H and 13C NMR analyses. As one
With an efficient route to 7 in hand, we next turned
our attention to the RCM reaction from the intermediary
7. Thus, the isolated 7 was subjected to the RCM
can see from Table 1, an increase of the substrate
concentration seemed to diminish the RCM reaction,
probably due to a competitive polymerization reaction.
It should be noteworthy that the RCM product was
obtained along with a small amount of the ADM product
7 and the tandem ADM-RCM product 8. The contents
of these products tended to increase as the substrate
(13) Warwel, S.; Ka¨tker, H. Synthesis 1987, 935.
(14) The ring-opening metathesis in the case of the compound ii
proceeded in 12% yield to afford iii, together with the recovered ii
(88%). The different reactivities of ii and 6 are probably due to a steric
factor.
(11) Methylene chloride was the most effective solvent for the
metathesis reaction of 5 and was used throughout the present study.
(12) In our preliminary experiments using desmethylated model
compound i, the RCM reaction occurred more rapidly than for 5. The
acyclic diene i was converted to ii under high dilution conditions
(substrate concentration, 2.9 mM).

4744 J . Org. Chem., Vol. 63, No. 14, 1998
Arakawa et al.
Sch em e 1
Sch em e 2a
Exp er im en ta l Section
Gen er a l In for m a tion . All reactions, except for catalytic
hydrogenation reactions, were carried out in an inert (Ar or
N2) atmosphere. THF was distilled from sodium/benzophe-
none ketyl. CH2Cl2 was distilled from calcium hydride. The
metathesis catalyst 3 was prepared in our laboratory according
to the literature.3b Coupling constants (J ) are reported in hertz.
1-O-Ben zyl-2,3-b is-O-[(3R,7R,11S,15S)-3,7,11,15-t et r a -
m eth ylh ep ta d ec-16-en yl]-sn -glycer ol (5). To a suspension
of methyltriphenylphosphonium bromide (331 mg, 0.927 mmol)
in THF (8 mL) was added nBuLi (1.59 M in hexane, 0.580 mL,
0.922 mmol) at -78 °C, and the mixture was stirred at -78
°C for 30 min and then at room temperature for 30 min. The
mixture was recooled to -78 °C and a solution of dialdehyde
410b (139 mg, 0.180 mmol) in THF (5 mL) was added. The
mixture was stirred at -78 °C for 15 min and at room
temperature for 1 h. Saturated NH4Cl (10 mL) was added and
the mixture was extracted twice with ether. The combined
organic layer was washed with brine, dried (Na2SO4), filtered,
and concentrated to dryness. The residue was chromato-
graphed over silica gel with hexanes-EtOAc (50:1 v/v) to give
a
Reagents and conditions: (a) substrate concentration, 1.0 mM,
3 (20 mol %), CH2Cl2, reflux, 72 h; (b) H2, 10% Pd-C/EtOAc.
reaction with 3 under high dilution conditions. As
illustrated in Scheme 2, the RCM reaction of 7 in a
concentration of 1.0 mM proceeded smoothly to afford the
72-membered 8 in 45% yield, along with the recovered 7
(33%). The latter can of course be recycled. The geo-
metrical isomer ratio of 8 was almost similar (E/ Z )
10:1) to the case of 6.
5 (131 mg, 95%) as an oil. [R]21 +6.63° (c 0.89, CHCl3). 1H
D
NMR (400 MHz): δ 0.84 (d, J ) 6.6, 9H), 0.86 (d, J ) 6.6,
9H), 0.98 (d, J ) 6.6, 6H), 1.00-1.70 (m, 46H), 2.10 (m, 2H),
3.42-3.66 (m, 9H), 4.55 (s, 2H), 4.93 (ddd, J ) 1.7, 2.0, and
10, 2H), 4.94 (ddd, J ) 1.2, 1.7, and 17, 2H), 5.69 (ddd, J )
7.6, 10, and 17, 2H), 7.25-7.34 (m, 5H). 13C NMR (100 MHz):
δ 19.68, 19.72, 19.76, 20.24, 24.36, 24.48, 24.62, 29.80, 29.88,
32.74, 32.80, 36.63, 36.97, 37.09, 37.39, 37.46, 37.51, 37.76,
68.87, 69.95, 70.30, 70.78, 73.34, 77.93, 112.20, 127.48, 127.56,
128.29, 138.42, 144.98. IR (neat): 908, 1462, 1639 cm-1. Anal.
Calcd for C52H94O3: C, 81.40; H, 12.35. Found: C, 81.15; H,
12.61.
Finally, the obtained 6 and 8 were separately converted
by catalytic hydrogenation to the 36-membered lipid 1
and to a mixture of 72-membered lipids 2a and 2b,
respectively (Scheme 2). All spectroscopic data of the
synthesized 1 and the mixture of 2a and 2b were
completely identical with those reported.10
In summary, we have successfully shown a convenient
synthesis of both 36- and 72-membered lipids from the
same starting material via the olefin metathesis reaction,
while the efficiency of the cyclization steps by RCM
leading to these macrocyclic lipids is comparable to the
McMurry coupling.10 The present synthetic strategy for
the 72-membered lipids is the first example toward
natural products by means of the conceptual tandem
ADM-RCM reaction.
(2S,7R,11R,15S,19S,22S,26S,30R,34R)-2-Ben zyloxym eth -
yl-7,11,15,19,22,26,30,34-octam eth yl-1,4-dioxacycloh exatr i-
a con t-20-en e (6). To a refluxing solution of diene 5 (32 mg,
0.042 mmol) in CH2Cl2 (5 mL) was added a purple solution of
3 (10 mg, 0.012 mmol, 29 mol %) in CH2Cl2 (6 mL). The
mixture was refluxed for 42 h. After concentrating the
mixture, the residue was purified by flash chromatography
over silica gel with hexanes-EtOAc (25:1) to afford 6 (24 mg,
79%; E/Z ) ca. 7:1) as an oil. 1H NMR (400 MHz): δ 0.83 (d,
J ) 6.4, 6H), 0.84 (d, J ) 6.4, 6H), 0.87 (d, J ) 6.6, 6H), 0.94

An Olefin Metathesis Approach to Membrane Lipids
J . Org. Chem., Vol. 63, No. 14, 1998 4745
(d, J ) 6.6, 6H), 1.00-1.70 (m, 46H), 2.01 (m, 2H), 3.46-3.64
(m, 9H), 4.55 (s, 2H), 5.10 (dd, J ) 2.4 and 5.1, 1.75H), 5.22
(dd, J ) 2.0 and 4.2, 0.25H), 7.26-7.34 (m, 5H). 13C NMR
(100 MHz): δ 19.78, 19.85, 21.82, 24.50, 25.06, 29.61, 29.74,
32.85, 32.87, 36.65, 36.98, 37.23, 37.33, 37.36, 37.46, 37.49,
37.77, 68.59, 69.71, 70.30, 71.45, 73.36, 77.94, 127.52, 127.58,
128.31, 134.18, 134.98, 138.38. IR (neat): 968, 1462, 1736
cm-1. EI-MS m/z (rel intensity): 739 (M+, 7), 648 (M+ - CH2-
Ph, 100), 633 (43), 556 (20). Anal. Calcd for C50H90O3: C,
81.24; H, 12.27. Found: C, 81.02; H, 12.46.
(2R,7R,11R,15S,19S,22S,26S,30R,34R)-2-Hydr oxym eth yl-
7,11,15,19,22,26,30,34-octa m eth yl-1,4-d ioxa cycloh exa tr ia -
con ta n e (1). A mixture of 6 (15 mg, 21 µmol) and 10% Pd-C
(17 mg) in EtOAc (5 mL) was stirred for 21 h under a hydrogen
atmosphere at room temperature. The catalyst was filtered
through a pad of Celite and washed with EtOAc. The filtrate
and washings were combined and concentrated to dryness. The
residue was chromatographed over silica gel with hexanes-
EtOAc (10:1) to give 1 (10 mg, 75%) as an oil. [R]20 +8.22 °
D
(c 1.01, CHCl3). 1H NMR (400 MHz): δ 0.85 (d, J ) 6.6, 12H),
0.88 (d, J ) 6.6, 6H), 0.89 (d, J ) 6.3, 6H), 1.00-1.70 (m, 52H),
2.15 (br, 1H), 3.46-3.71 (m, 9H). 13C NMR (100 MHz): δ
19.85, 19.93, 20.03, 20.09, 23.97, 24.27, 24.42, 29.72, 29.77,
32.41, 32.47, 32.60, 32.67, 32.77, 33.03, 33.58, 34.16, 36.54,
36.68, 37.00, 37.26, 63.03, 68.53, 70.00, 71.19, 78.38. IR
(neat): 1462, 3446 cm-1. EI-MS m/z (rel intensity): 651 (M+,
100), 633 (M+ - H2O, 60), 621 (59). Anal. Calcd for C43H86O3:
C, 79.32; H, 13.31. Found: C, 79.03; H, 13.40.
Th e ADM Rea ction of 5. To a stirred solution of diene 5
(25 mg, 0.032 mmol) in CH2Cl2 (0.2 mL) was added a purple
solution of 3 (5.4 mg, 6.6 µmol) in CH2Cl2 (0.10 mL) at room
temperature. The mixture was stirred at room temperature
for 9 h. The solution was passed through a pad of silica gel.
After concentration, the residue was chromatographed over
silica gel with hexanes-EtOAc (25:1) to afford 7 (8.4 mg, 35%)
1
and the recovered 5 (14.3 mg, 57%). 7; H NMR (400 MHz):
δ 0.83 (d, J ) 6.4, 6H), 0.84 (d, J ) 6.6, 12H), 0.86 (d, J ) 6.4,
12H), 0.87 (d, J ) 6.8, 6H), 0.95 (d, J ) 6.8, 6H), 0.98 (d, J )
6.8, 6H), 1.00-1.70 (m, 92H), 1.95-2.20 (br, 4H), 3.42-3.66
(m, 18H), 4.55 (s, 4H), 4.89 (ddd, J ) 1.7, 2.0, and 10, 2H),
4.94 (ddd, J ) 1.2, 2.0, and 17, 2H), 5.10 (dd, J ) 2.4 and 5.4,
0.2H), 5.17 (dd, J ) 2.2 and 4.6, 1.8H), 5.81 (ddd, J ) 7.6, 10,
and 17, 2H), 7.26-7.34 (m, 10H). 13C NMR (100 MHz): δ
19.68, 19.72, 19.75, 20.23, 21.17, 24.37, 24.48, 24.51, 24.63,
24.73, 29.69, 29.83, 29.91, 32.75, 32.82, 36.65, 36.70, 36.98,
37.11, 37.40, 37.47, 37.54, 37.75, 68.89, 69.97, 70.34, 70.80,
73.35, 77.95, 112.20, 127.48, 127.57, 128.29, 134.40, 134.57,
138.44, 145.01. IR (neat): 908, 1462, 1734 cm-1. EI-MS m/z
(rel intensity): 1505 (M+, 4), 1414 (M+ - CH2Ph, 100), 1308
(55). Anal. Calcd for C102H184O6: C, 81.32; H, 12.31. Found:
C, 81.19; H, 12.61.
Tetr a eth er Lip id s 2a a n d 2b. A mixture of 8 (7.4 mg,
5.0 µmol) and 10% Pd-C (9.4 mg) in EtOAc (5 mL) was stirred
for 34 h under an hydrogen atmosphere at room temperature.
The catalyst was filtered through a pad of Celite and washed
with EtOAc. The filtrate and washings were combined and
concentrated to dryness. The residue was purified by flash
chromatography over silica gel with hexanes-EtOAc (4:1) to
give a mixture of 2a and 2b (5.1 mg, 78%). [R]22 +7.31° (c
D
0.51, CHCl3). 1H NMR (400 MHz): δ 0.85 (d, J ) 6.4, 24H),
0.88 (d, J ) 6.6, 12H), 0.89 (d, J ) 6.6, 12H), 1.00-1.70 (m,
104H), 2.17 (br, 2H), 3.46-3.75 (m, 18H). 13C NMR (100
MHz): δ 19.76, 19.83, 19.85, 24.37, 24.46, 29.79, 29.84, 32.79,
33.06, 34.30, 36.57, 37.06, 37.37, 37.51, 63.08, 68.59, 70.09,
71.06, 78.34. IR (neat): 1462, 3435 cm-1
. EI-MS m/z (rel
intensity): 1301 (M+, 76), 1283 (M+ - H2O, 54), 1271 (61),
650 (100). Anal. Calcd for C86H172O6: C, 79.32; H, 13.31.
Found: C, 79.02 H, 13.59.
Th e RCM Rea ction of 7. To a refluxing solution of 7 (17
mg, 11.2 µmol) in CH2Cl2 (10 mL) was added a purple solution
of 3 (2.0 mg, 22 mol %) in CH2Cl2 (1.0 mL). The mixture was
refluxed for 72 h. After concentrating the mixture, the residue
was chromatographed over silica gel with hexanes-EtOAc (30:
1) to afford 8 (7.4 mg, 45%) and the recovered 7 (5.6 mg, 33%).
Ack n ow led gm en t. This work was supported in part
by a Grant-in-Aid for Scientific Research from the
Ministry of Education, Science, Sports, and Culture,
J apan.
1
8: H NMR (400 MHz): δ 0.83 (d, J ) 6.4, 12H), 0.84 (d, J )
6.6, 12H), 0.87 (d, J ) 6.6, 12H), 0.94 (d, J ) 6.8, 12H), 0.98-
1.70 (m, 92H), 2.02 (br, 4H), 3.45-3.66 (m, 18H), 4.55 (s, 4H),
5.15 (dd, J ) 2.2 and 4.6, 3.7H), 5.19 (dd, J ) 2.0 and 4.6,
0.3H), 7.26-7.34 (m, 10H). 13C NMR (100 MHz): δ 19.75,
19.81, 21.37, 24.39, 24.50, 24.80, 29.70, 29.76, 29.86, 32.77,
32.82, 36.64, 36.87, 37.10, 37.40, 37.44, 37.48, 37.51, 37.60,
68.81, 69.91, 70.32, 70.96, 73.35, 77.95, 127.49, 127.57, 128.30,
134.67, 138.42. IR (neat): 968, 1462, 1743 cm-1. EI-MS m/z
(rel intensity): 1477 (M+, 4), 1386 (M+ - CH2Ph, 100), 1280
(57). Anal. Calcd for C100H180O6: C, 81.24; H, 12.27. Found:
C, 81.24; H, 12.42.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra for the compounds 5-8, 1, and 2 and MS spectra for
the compounds 6-8, 1, and 2 (17 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 O980472K