Total synthesis of (+)- and (-)-duryne: A potent anticancer agent from the marine sponge cribrochalina dura. Establishment of the central double bond geometry and the absolute configuration of the chiral centers

Article abstract of DOI:10.1021/jo702399j

(Chemical Equation Presented) Duryne is a C30 polyacetylenic alcohol with C2 symmetry. Despite its potent cytotoxicity, its central double bond geometry and the absolute configuration of the chiral centers were not determined. We report the total synthese

Full text of DOI:10.1021/jo702399j

Total Synthesis of (+)- and (-)-Duryne: A Potent Anticancer Agent
from the Marine Sponge Cribrochalina Dura. Establishment of the
Central Double Bond Geometry and the Absolute Configuration of
the Chiral Centers
Benjamin W. Gung* and Ann O. Omollo
Department of Chemistry & Biochemistry, Miami UniVersity, Oxford, Ohio 45056
gungbw@muohio.edu
ReceiVed NoVember 9, 2007
Duryne is a C30 polyacetylenic alcohol with C2 symmetry. Despite its potent cytotoxicity, its central
double bond geometry and the absolute configuration of the chiral centers were not determined. We
report the total syntheses of both enantiomers of the anticancer natural product (+)-duryne and the
establishment of its stereochemistry by synthesizing both geometric isomers. The natural (+)-duryne is
identified as (15Z) and (3S,28S) as shown in structure 1. The autoxidation/Wittig coupling reaction was
employed to synthesize the central (Z)-olefin. The stereochemistry of the (E)-alkene isomer was constructed
stereoselectively by using LiAlH4 reduction of the corresponding alkyne. The absolute configurations of
the chiral centers are established by using Burgess’ enzymatic resolution procedure with Pseudomonas
AK lipase.
Introduction
utilized the monoprotected diacetylene alcohol to prepare the
(15E,R,R)-isomer of duryne.4 The C2 symmetry of the molecule
renders the two protons on the central double bond equivalent;
hence no indicative coupling constant is available. All other
spectroscopic data seem to provide no definite conclusions.
In recent years, we have been involved in the total synthesis
of biologically active acetylenic alcohols and have reported the
syntheses of several polyacetylene natural products.5-8 We set
out in this study to establish the configuration of the central
double bond and the absolute configurations of the stereocenters
Duryne was isolated in 1987 from the marine sponge
Cribrochalina dura by Wright and co-workers.1 It was found
that duryne inhibits the growth of several human tumor cell
lines including leukemia, colon, lung, gastric, and breast cancers.
It exhibits an IC50 of 0.07 µg/mL against p388 murine leukemia,
and minimum inhibitory concentrations of 0.1 µg/mL against
other human tumor cell lines. However, the geometry of the
central C15dC15′ olefin and the absolute stereochemistry of the
chiral centers were not determined.2 Two previous synthetic
studies have been published. None was able to correlate the
stereochemistry of the synthetic sample with the natural duryne.
The first study by Deshpande produced racemic mixtures of
duryne.3 The second study by Sharma and Chattopadhyay
(4) Sharma, A.; Chattopadhyay, S. An efficient derivation of the versa-
tile chiron antipode 1-tert-butyldimethylsilylpenta-1,4-diyn-3-ol: Appli-
cation to the synthesis of (15E,R,R)-duryne.J. Org. Chem. 1998, 63, 6128-
6131.
(5) Gung, B. W.; Dickson, H. Total synthesis of (-)-minquartynoic
acid: An anti-cancer, anti-HIV natural product.Org. Lett. 2002, 4, 2517-
2519.
(6) Gung, B. W.; Kumi, G. J. Org. Chem. Total synthesis of (S)-(-)-
(E)-15,16-dihydrominquartynoic acid: A highly potent anticancer agent.2004,
69, 3488-3492.
(7) Gung, B. W.; Gibeau, C.; Jones, A. Total synthesis of two novel
brominated acetylenic diols (+)-diplyne C and E: stereoselective construc-
tion of the (E)-1-bromo-1-alkene. Tetrahedron: Asymmetry 2005, 16, 3107-
3114.
(1) Wright, A. E.; McConnell, O. J.; Kohmoto, S.; Lui, M. S.; Thompson,
W.; Snader, K. M. Duryne, A New Cytotoxic Agent From The Marine
Sponge Cribrochalina-Dura. Tetrahedron Lett. 1987, 28, 1377-1380.
(2) Vrettou, M.; Gray, A. A.; Brewer, A. R. E.; Barrett, A. G. M.
Strategies for the synthesis of C-2 symmetric natural products-a review.
Tetrahedron 2007, 63, 1487-1536.
(3) Deshpande, V. H.; Upadhye, B. K.; Wakharkar, R. D. Synthesis Of
(+/-)Duryne. Tetrahedron Lett. 1989, 30, 1991-1992.
10.1021/jo702399j CCC: $40.75 © 2008 American Chemical Society
Published on Web 01/10/2008
J. Org. Chem. 2008, 73, 1067-1070
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Gung and Omollo
in structure to adociacetylene, which we have successfully
resolved using lipase from Pseudomonas sp.15 For most second-
ary alcohols, the rate of acylation is faster for the (R)-
configuration than for the (S)-configuration. However, for the
acetylenic alcohol 4 the alcohol with (S,S) configuration is
acylated faster because the small acetylenic group has a higher
priority in the nomenclature system. From these considerations
and the data obtained, we surmise that the natural duryne has a
(Z)-central double bond and (S,S)-configurations at the chiral
centers. However, in order to remove the doubt that the
corresponding isomer with a central (E) double bond might have
a similar optical rotation, we decided to synthesize the (E)-
isomer and resolve the racemic mixture as well.
FIGURE 1. Anticancer agent, natural (S)-(+)-duryne, from the marine
sponge Cribrochalina dura.
for the natural duryne. We are pleased to report a successful
correlation of our synthetic sample and the reported data for
the natural duryne.
Results and Discussion
The (E)-geometry of the central double bond of the trans
isomer was constructed with LiAlH4 reduction of an internal
alkyne precursor.3 The racemic mixture of the (E)-isomer 8 was
prepared following the procedures by Deshpande.3 After
enzymatic resolution of 8 the optical activity obtained for the
(15E), (3S,28S)-diol 12 is [R]D 13.8 and that for the (15E), (3R,-
28R)-diol 11 is [R]D -13.0. Thus by synthesizing both geometric
isomers of duryne and the subsequent enzymatic resolution, we
conclude that the natural (+)-duryne reported by Wright et al.
has a central double bond geometry of (Z) and absolute
configuration of (S,S) as shown in structure 1. This conclusion
not only is consistent with all experimental data reported in this
study, but it is also consistent with several known C2 symmetric
acetylenic alcohols isolated from marine sources.16-19 They are
listed in Table 1 for comparison purposes.
Our synthetic effort started with the known (Z)-alkene diol
(2),9,10 which was prepared in three steps from the commercially
available ω-bromoundecanoic acid, Scheme 1. The ω-bromoacid
was converted to the corresponding methyl ester, which was
treated with Ph3P in acetonitrile to yield the phosphonium salt,
using a reported procedure.11 The (Z)-geometry of the central
double bond was established by the autoxidation of the Wittig
reagent generated in situ as reported by Poulain and co-workers.9
Oxygen was bubbled through the mixture during the reaction
as reported by Capon.12 The diol 2 was converted to the
dialdehyde 3 through a two-step sequence: (1) PCC oxidation
to the corresponding dialdehyde and (2) Wittig reaction of the
dialdehyde with Ph3PdCHCHO to yield dial 3. The addition
of acetylenic magnesium bromide reagent to dial 3 produced
the precursor 4 for enzymatic resolution.
The general procedures of Burgess were followed using lipase
AK from pseudomonas sp for the enzymatic resolution of the
acetylenic alcohol 4.13,14 The progress of the reaction was
Summary
The central olefin geometry and the absolute configuration
of the potent anticancer polyacetylenic alcohol natural (+)-
duryne have been established. Through the total syntheses of
both (Z) and (E) isomers and the subsequent enzymatic
resolution of each racemic mixture, natural duryne is identified
as (15Z) and (3S,28S) as shown in structure 1. This conclusion
is consistent with naturally occurring C2 symmetric acetylenic
alcohols from marine sources.
1
followed by both thin layer chromatography and H NMR to
ensure a clean kinetic resolution of the enantiomers. The
separation of the diacetate 5, monoacetate 6, and the diol 7 was
done by column chromatography. Diol 7 has a melting point of
41-42 °C and an optical rotation of [R]D -26.3. The removal
of the acetate group from 5 yields diol 1, which gives an optical
rotation of [R]D 27.1 and a melting point of 43-45 °C. These
values are very close to those reported1 for the natural duryne:
[R]D 29 and 44-45 °C. In a study of enzymatic resolution of
secondary alcohols by the lipases from Pseudomonas sp.
Burgess proposed a simple active site model for predicting
enantioselectivity.13 This model predicts that alcohols resolved
most efficiently have one small and one relatively large group
attached to the hydroxylmethine functionality. Duryne is similar
Experimental Section
Triaconta-2E,13Z,24E-triene-1,26-dialdehyde (3). Diol 2 (400
mg, 1.06 mmol) was dissolved in CH2Cl2 (5 mL). This mixture
was added to a stirred suspension consisting of pyridinium
chlorochromate (684 mg, 3.16 mmol) and Celite (684 mg) in CH2-
Cl2 (8 mL) under nitrogen. After 2 h the starting material
disappeared and the reaction mixture was diluted with Et2O and
then filtered through a pad of Florosil. This was thoroughly rinsed
(8) Gung, B. W.; Fox, R. M.; Falconer, R.; Shissler, D. Total synthesis
of two naturally occurring polyacetylenic glucosides (-)-bidensyneoside
A1 and B, and an analogue of (-)-bidensyneoside C. Tetrahedron:
Asymmetry 2006, 17, 40-46.
(9) Poulain, S.; Noiret, N.; Patin, H. An easy access to symmetrical
Z-olefins from phosphorus ylides. Tetrahedron Lett. 1996, 37, 7703-7706.
(10) Higley, M. N.; Pollino, J. M.; Hollembeak, E.; Weck, M. A modular
approach toward block copolymers. Chem.-Eur. J. 2005, 11, 2946-2953.
(11) Dawson, M. I.; Vasser, M. Synthesis Of Prostaglandin Synthetase
Substrate Analogs. 1. (Z)-14-Hydroxy-12,13-Methano-8-Nonadecenoic Acid.
J. Org. Chem. 1977, 42, 2783-2785.
(12) Capon, R. J.; Skene, C.; Liu, E. H.; Lacey, E.; Gill, J. H.; Heiland,
K.; Friedel, T. The isolation and synthesis of novel nematocidal dithiocy-
anates from an Australian marine sponge, Oceanapia sp. J. Org. Chem.
2001, 66, 7765-7769.
(13) Burgess, K.; Jennings, L. D. Enantioselective Esterifications of
Unsaturated Alcohols Mediated by a Lipase Prepared from Pseudomonas
Sp. J. Am. Chem. Soc. 1991, 113, 6129-6139.
(14) Burgess, K.; Jennings, L. D. Kinetic Resolutions of Chiral Unsatur-
ated Alcohols That Cannot Be Resolved Efficiently Via Enantioselective
Epoxidation. J. Am. Chem. Soc. 1990, 112, 7434-7436.
(15) Gung, B. W.; Dickson, H.; Shockley, S. A concise synthesis of (+)-
and (-)-adociacetylene B. Tetrahedron Lett. 2001, 42, 4761-4763.
(16) Braekman, J. C.; Daloze, D.; Devijver, C.; Dubut, D.; van Soest,
R. W. M. A new C-20 polyacetylene from the sponge Callyspongia
pseudoreticulata. J. Nat. Prod. 2003, 66, 871-872.
(17) Kobayashi, M.; Mahmud, T.; Tajima, H.; Wang, W. Q.; Aoki, S.;
Nakagawa, S.; Mayumi, T.; Kitagawa, I. Marine natural products. 36.
Biologically active polyacetylenes, adociacetylenes A, B, C, and D, from
an Okinawan marine sponge of Adocia sp.Chem. Pharm. Bull. 1996, 44,
720-724.
(18) Isaacs, S.; Kashman, Y.; Loya, S.; Hizi, A.; Loya, Y. Petrosynol
And Petrosolic Acid, 2 Novel Natural Inhibitors Of The Reverse-
Transcriptase Of Human-Immunodeficiency-Virus From Petrosia Sp.
Tetrahedron 1993, 49, 10435-10438.
(19) Fusetani, N.; Shiragaki, T.; Matsunaga, S.; Hashimoto, K. Bioactive
Marine Metabolites. 20. Petrosynol And Petrosynone, Antimicrobial C30
Polyacetylenes From The Marine Sponge Petrosia Sp-Determination Of The
Absolute-Configuration. Tetrahedron Lett. 1987, 28, 4313-4314.
1068 J. Org. Chem., Vol. 73, No. 3, 2008

Total Synthesis of (+)- and (-)-Duryne
SCHEME 1
SCHEME 2
TABLE 1. Absolute Configurations of Naturally Occurring C2-Symmetric Acetylenic Alcohols
name
chain length
central moiety
[R]D
config.
origin
adociacetylene
petrosynol
C20 acetylenic alcohol
duryne (natural)
30
30
20
30
furan
+21.7
+107
+26
S,S
S,S
S,S
S,S
Adocia sp.
Petrocia sp.
Callyspongia pseudoreticulata
Cribrochalina dura
CdC, (Z)
-CH2CH2
CdC, (Z)
+29
with ether followed by removal of the solvent under reduced
pressure. The crude product so obtained was subsequently dissolved
in benzene (8 mL) then was treated with Ph3PCHdCHO (1.26 g,
4.16 mmol). The mixture was refluxed for 9 h then diluted with
Et2O. Upon completion of starting material the reaction mixture
was filtered through a pad of silica. The filtrate was concentrated
under reduced pressure and purified via column chromatography
to afford 3 as a yellow oil (236 mg, 61%): IR 1464, 1638, 1687,
2854, 2925 cm-1; 1H NMR (300 MHz, CDCl3) δ 1.2-1.5 (m, 28H),
1.93 (m, 4H), 2.27-2.33 (m, 4H), 5.36 (m, 2H), 6.09 (dd, J )
15.5, 6.9 Hz, 2H), 6.8 (dt, J ) 15.6, 6.7 Hz, 2H), 9.48 (d, J ) 7.9
Hz, 2H); 13C NMR (CDCl3, 75 MHz) δ 22.1, 27.8, 28.6, 29.1, 29.3,
29.4, 29.6, 32.6, 32.7, 130.3, 132.9, 158.9, 194.1; HRMS calcd for
C26H44O2 (M + Na) 411.3239, found 411.3238.
Triaconta-4E,15Z,26E-triene-1,29-diyne-3,28-diol (4). To a
solution of ethynylmagnesium bromide (2.88 mL, 1.44 mmol, 0.5
M in THF) at 0 °C under nitrogen was added, dropwise, the
dialdehyde 3 (202 mg, 0.52 mmol) in THF (4 mL). The reaction
progress was monitored by TLC. At the completion of the starting
material the reaction mixture was quenched using saturated NH4-
Cl solution and the organic layer was extracted using EtOAc. The
combined organic layers were neutralized using aq NaHCO3 and
dried over MgSO4. Purification was effected via column chroma-
tography to afford 4 as a pale yellow solid (196 mg, 86%): mp
36-37 °C; IR 1461, 2146, 2850, 2919, 2999, 3288 cm-1; 1H NMR
(300 MHz, CDCl3) δ 1.24-1.39 (m, 28 H), 1.92-2.07 (m, 8 H),
2.54 (d, J ) 2.1 Hz, 2 H), 4.82 (t, J ) 5.9 Hz, 2 H), 5.36 (m, 2 H),
5.59 (dd, J ) 15.3, 6.5 Hz, 2 H), 5.89 (dt, J ) 15.3, 6.6 Hz, 2 H);
13C NMR (75 MHz, CDCl3) δ 28.8, 29.15, 29.18, 29.4, 29.5, 29.6,
29.7, 31.9, 32.6, 62.8, 73.9, 83.4, 128.4, 130.4, 134.6; HRMS calcd
for C30H48O2 (M + Na) 463.3552, found 463.3547.
Enzymatic Resolution of 4. A flask was charged with lipase
AK Amano ‘20’ (360 mg), molecular sieves (360 mg), hexanes
(12 mL), vinyl acetate (0.6 mL, 6.58 mmol), and the racemic diol
(180 mg, 0.41 mmol). The mixture was stirred at room temperature
for 3 h. The progress of the reaction was monitored by TLC and
1H NMR. When the amount of the diacetate was about the same
as the amount of the diol, the reaction was stopped. The reaction
mixture was filtered over a pad of Celite then separated by flash
column chromatography to afford the diacetate 5 (65 mg, 18%), as
an oil: [R]D +15.3 (c 0.03, CHCl3); IR 1461, 1739, 2125, 2854,
1
2925 cm-1; H NMR (300 MHz, CDCl3) δ 1.24-1.38 (m, 28H),
1.92-2.05 (m, 8H), 2.07 (s, 6H), 2.53 (d, J ) 2.1 Hz, 2H), 5.35
(m, 2H), 5.51 (dd, J ) 15.3, 6.5 Hz, 2H), 5.8 (d, J ) 6.1 Hz, 2H),
5.9 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 21.1, 28.6, 29.1, 29.2,
29.4, 29.5, 29.6, 29.7, 32.0, 32.6, 64.1, 74.7, 80.0, 124.3, 130.3,
J. Org. Chem, Vol. 73, No. 3, 2008 1069

Gung and Omollo
137.2, 169.7; MS calcd for C34H52O4 (M + Na) 547.3, found 547.4.
The monoacetate 6 (168 mg, 45%) as an oil: [R]D +7.2 (c 0.11,
29.5, 29.6, 29.7, 32.0, 32.6, 64.1, 74.7, 80.0, 124.3, 130.3, 137.2,
169.7. The monoacetate 10 (94 mg, 41%) as an oil: [R]D -3.9 (c
1
1
CDCl3); IR 1461, 1739, 2126, 2848, 2950, 3340 cm-1; H NMR
0.09, CDCl3); IR 1461, 1739, 2126, 2848, 2950, 3340 cm-1; H
(300 MHz, CDCl3) δ 1.24-1.38 (m, 28H), 1.9-2.05 (m, 8H), 2.07
(s, 3H), 2.53 (d, J ) 2.1 Hz, 2H), 4.82 (t, J ) 5.9 Hz, 1H), 5.35
(m, 2H), 5.4-5.6 (m, 2H), 5.8 (d, J ) 6.2 Hz, 1H), 5.9-6.0 (m,
2H); 13C (75 MHz, CDCl3) δ 21.1, 28.6, 28.8, 29.1, 29.2, 29.4,
29.45, 29.5, 29.53, 29.6, 31.9, 32.0, 32.6, 62.8, 64.1, 73.9, 74.7,
80.0, 83.4, 124.3, 128.4, 130.4, 130.7, 134.4, 137.2, 169.7; MS
calcd for C32H50O3 (M + Na) 505.4, found 505.4. The diol 7 (80
mg, 21%) as a solid: [R]D -26.3 (c 0.024, CDCl3); mp 41-
NMR (300 MHz, CDCl3) δ 1.24-1.38 (m, 28H), 1.9-2.05 (m,
8H), 2.07 (s, 3H), 2.53 (d, J ) 2.1 Hz, 2H), 4.82 (t, J ) 5.9 Hz,
1H), 5.35 (m, 2H), 5.4-5.6 (m, 2H), 5.8 (d, J ) 6.2 Hz, 1H), 5.9-
6.0 (m, 2H); 13C (75 MHz, CDCl3) δ 21.1, 28.6, 28.8, 29.1, 29.2,
29.4, 29.45, 29.5, 29.53, 29.6, 31.9, 32.0, 32.6, 62.8, 64.1, 73.9,
74.7, 80.0, 83.4, 124.3, 128.4, 130.4, 130.7, 134.4, 137.2, 169.7.
The diol 11 (41 mg, 19%) as a solid: [R]D -13 (c 0.07, CDCl3);
1
mp 34-35 °C; IR 1461, 2149, 2850, 2918, 2999, 3288 cm-1; H
1
42 °C; IR 1461, 2149, 2850, 2918, 2999, 3288 cm-1; H NMR
NMR (300 MHz, CDCl3) δ 1.24-1.39 (m, 28H), 1.92-2.07 (m,
8H), 2.54 (d, J ) 2.1 Hz, 2H), 4.82 (t, J ) 5.9 Hz, 2H), 5.36 (m,
2H), 5.59 (dd, J ) 15.3, 6.5, Hz, 2H), 5.89 (dt, J ) 15.3, 6.6 Hz,
2H); 13C NMR (75 MHz, CDCl3) δ 28.8, 29.15, 29.18, 29.4, 29.5,
29.6, 29.7, 31.9, 32.6, 62.8, 73.9, 83.4, 128.4, 130.4, 134.6; HRMS
calcd for C30H48O2 (M + Na) 463.3552, found 463.3547.
(300 MHz, CDCl3) δ 1.24-1.39 (m, 28 H), 1.92-2.07 (m, 8 H),
2.54 (d, J ) 2.1 Hz, 2H), 4.82 (t, J ) 5.9 Hz, 2H), 5.36 (m, 2H),
5.59 (dd, J ) 15.3, 6.5 Hz, 2H), 5.89 (dt, J ) 15.3, 6.6, 2H); 13C
NMR (75 MHz, CDCl3) δ 28.8, 29.15, 29.18, 29.4, 29.5, 29.6, 29.7,
31.9, 32.6, 62.8, 73.9, 83.4, 128.4, 130.4, 134.6; HRMS calcd for
C30H48O2 (M + Na) 463.3552, found 463.3547.
Triaconta-4E,15E,26E-triene-1,29-diyne-3S,28S-diol (12). The
diacetate 9 (26 mg, 0.05 mmol) and K2CO3 (3 mg, 0.02 mmol)
were dissolved in methanol (2 mL). The reaction mixture was stirred
at rt for 2 h then quenched with diluted aq HCl and the organic
layer was extracted with EtOAc. Purification was effected via
column chromatography to afford 12 as a solid (18 mg, 87%); [R]D
13.8 (c 0.018, CHCl3); mp 37-39 °C; IR 1461, 2128, 2850, 2918,
Triaconta-4E,15Z,26E-triene-1,29-diyne-3S,28S-diol (1). The
diacetate 5 (52 mg, 0.104 mmol) and K2CO3 (10 mg, 0.064 mmol)
were dissolved in methanol (4 mL). The reaction mixture was stirred
at rt for 2 h then quenched with diluted aq HCl and the organic
layer was extracted with EtOAc. Purification was effected via
column chromatography to afford 1 as a solid (42 mg, 87%): [R]D
+27.1 (c 0.017, CHCl3); mp 43-45 °C; IR 1461, 2128, 2850, 2918,
1
2999, 3288 cm-1; H NMR (300 MHz, CDCl3) δ 1.24-1.39 (m,
1
2999, 3288 cm-1; H NMR (300 MHz, CDCl3) δ 1.24-1.39 (m,
28 H), 1.92-2.07 (m, 8 H), 2.54 (d, J ) 2.1 Hz, 2H), 4.82 (t, J )
5.9 Hz, 2 H), 5.36 (m, 2 H), 5.59 (dd, J ) 15.3, 6.5, Hz, 2 H), 5.89
(dt, J ) 15.3, 6.6 Hz, 2 H); 13C NMR (75 MHz, CDCl3) δ 28.8,
29.15, 29.18, 29.4, 29.5, 29.6, 29.7, 31.9, 32.6, 62.8, 73.9, 83.4,
128.4, 130.4, 134.6; HRMS calcd for C30H48O2 (M + Na) 463.3552,
found 463.3547.
28 H), 1.92-2.07 (m, 8 H), 2.54 (d, J ) 2.1 Hz, 2 H), 4.82 (t, J )
5.9 Hz, 2H), 5.36 (m, 2H), 5.59 (dd, J ) 15.3, 6.5, Hz, 2H), 5.89
(dt, J ) 15.3, 6.6 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 28.8,
29.15, 29.18, 29.4, 29.5, 29.6, 29.7, 31.9, 32.6, 62.8, 73.9, 83.4,
128.4, 130.4, 134.6; HRMS calcd for C30H48O2 (M + Na) 463.3552,
found 463.3547.
Acknowledgment. We are grateful for support from the
National Institutes of Health (GM069441). We thank Heather
Davis for technical assistance.
Enzymatic Resolution of 8. The same procedure described for
the resolution of 4 was employed. Separation was effected via
column chromatography to afford the diacetate 9 (54 mg, 21%), as
an oil: [R]D 9.7 (c 0.02, CHCl3); IR 1461, 1739, 2125, 2854, 2925
cm-1; 1H NMR (300 MHz, CDCl3) δ 1.24-1.38 (m, 28H), 1.92-
2.05 (m, 8H), 2.07 (s, 6H), 2.53 (d, J ) 2.1 Hz, 2H), 5.35 (m, 2H),
5.51 (dd, J ) 15.3, 6.5 Hz, 2H), 5.8 (d, J ) 6.1 Hz, 2H), 5.9 (m,
2H); 13C NMR (75 MHz, CDCl3) δ 21.1, 28.6, 29.1, 29.2, 29.4,
Supporting Information Available: General experimental
procedures and NMR spectra for compounds 1 and 3-6. This
materialisavailablefreeofchargeviatheInternetathttp://pubs.acs.org.
JO702399J
1070 J. Org. Chem., Vol. 73, No. 3, 2008