General preparation and controlled cyclization of acyclic terpenoids

Article abstract of DOI:10.1021/jo702303a

A general preparation method of the all-(E)-polyprenols 12 has been developed from readily available geranyl sulfone by the chain-extension process utilizing the C₅ unit 5 and the chain-termination process utilizing the C₅ unit 10 to

Full text of DOI:10.1021/jo702303a

SCHEME 1. Controlling the Electrophilic Cyclization of the
Polyprenyl Sulfones
General Preparation and Controlled Cyclization
of Acyclic Terpenoids
Jinchul Kuk,† Beom Soo Kim,‡ Heejung Jung,‡
Seyoung Choi,‡ Jung-Youl Park,‡,§ and Sangho Koo*,†,‡
Department of Nano Science and Engineering and
Department of Chemistry, Myong Ji UniVersity, Yongin,
Kyunggi-Do, 449-728, Korea
sangkoo@mju.ac.kr
ReceiVed October 24, 2007
to construct the diverse cyclic structures.3 It is desirable to have
a general, but still controllable, cyclization method for the
acyclic polyprenyl compounds in order to synthesize the diverse
cyclic terpenoids.
Terpenoid cyclization in nature is electrophilic, and various
acidic conditions in vitro have been found to induce the efficient
cyclization of the polyprenyl compounds as a mimic of the
biological process.4 These conditions were mostly very strong,
and unstoppable cyclization cascades of the polyprenyl sulfones
1 gave rise to the polycyclic terpenoid compounds 2, in which
deprotonation of the cyclized tertiary carbocation intermediates
produced the regioisomeric alkene products (R-, â-, and γ-forms
in Scheme 1).5 It was envisioned that the degree of the cycli-
zation cascades would be controlled by inserting a benzene-
sulfonyl group into the polyprenyl sulfone chain such as in
compound 3.6 The flat and rigid nature of the two consecutive
benzenesulfonyl moieties in compound 3 would prevent the
nearby carbon-carbon double bonds from taking the required
conformations for cyclization, thereby allowing the cyclization
only at the remote carbon-carbon double bonds (Scheme 1).
Since sulfone chemistry has been efficiently utilized in the chain-
extension process for isoprenoid synthesis,7 the controlled
cyclization, together with the chain-extension process using the
sulfonyl group, would constitute a general and efficient synthetic
method of the cyclized terpenoid compounds.
This research commenced with the preparation of compound
3 containing two consecutive prenyl sulfone moieties at the tail
end, which can be synthesized from the polyprenyl sulfones 1
utilizing our chain-extension strategy (Scheme 2).7 The poly-
prenyl sulfones 1 can be obtained from the corresponding
polyprenols by a straightforward sequence of reactions: bro-
mination and sulfonylation. It is not practical, however, to
purchase long-chain polyprenols such as geranylgeraniol and
geranylfarnesol. Thus, a direct chain-extension method from
readily available geranyl sulfone 1a (n ) 1) to the higher
homologous sulfones 1 (n ) 2 or higher) was investigated by
modifying the chain-extension procedure. Each iteration se-
quence in Scheme 2 produces a C5-extended polyallylic sulfone
A general preparation method of the all-(E)-polyprenols 12
has been developed from readily available geranyl sulfone
by the chain-extension process utilizing the C5 unit 5 and
the chain-termination process utilizing the C5 unit 10 together
with the chemoselective reductive desulfonylation. The
polyprenols 12 were converted to compounds 3 containing
two consecutive prenyl sulfone moieties at the tail end, which
underwent the controlled electrophilic cyclization only at the
carbon-carbon double bonds that were remote from the flat
and rigid benzenesulfonyl groups.
It is surprising that nature produces tens of thousands of cyclic
terpenoid secondary metabolites from just a few acyclic poly-
prenyl substrates: geranyl, farnesyl, and geranylgeranyl pyro-
phosphates.1 The terpene cyclase enzymes control the mode of
these diverse cyclizations to produce a plethora of cyclic
terpenoids from the simplest menthol to the much more complex
taxol.2 Organic chemists have challenged the total syntheses of
the biologically important cyclic terpenoids, in which each
specific cyclization method was applied to different substrates
*
To whom correspondence should be addressed. Phone: (+82)-31-330-
6185. Fax: (+82)-31-335-7248.
† Department of Nano Science and Engineering.
‡ Department of Chemistry.
§ Current address: C&C Research Lab. ChoongWae Pharma Corporation,
148-141, Annyeong-Dong, Hwaseong-Shi, Kyunggi-Do, 445-380, Korea.
(1) (a) Greenhagen, B.; Chappell, J. Proc. Natl. Acad. Sci. U.S.A. 2001,
98, 13479-13481. (b) Cane, D. E. In ComprehensiVe Natural Products
Chemistry; Barton, D., Nakanishi, K., Eds.; Elsevier: Oxford, UK, 1999;
Vol. 2.
(3) Maimone, T. J.; Baran, P. S. Nature Chem. Biol. 2007, 3, 396-407.
(4) Yoder, R. A.; Johnston, J. N. Chem. ReV. 2005, 105, 4730-4756.
(5) Kulcitki, V.; Ungur, N.; Vlad, P. F. Tetrahedron 1998, 54, 11925-
11934.
(6) The Friedel-Craft allylation of the prenyl group proceeded efficiently
without cyclization in the coenzyme Q-10 synthesis, due to the presence of
a benzenesulfonyl group; see: Min, J.-H.; Lee, J.-S.; Yang, J.-D.; Koo, S.
J. Org. Chem. 2003, 68, 7925-7927.
(7) Ji, M.; Choi, H.; Park, M.; Kee, M.; Jeong, Y. C.; Koo, S. Angew.
Chem., Int. Ed. 2001, 40, 3627-3629.
(2) (a) Caruthers, J. M.; Kang, I.; Rynkiewicz, M. J.; Cane, D. E.;
Christianson, D. W. J. Biol. Chem. 2000, 275, 25533-25539. (b) Starks,
C. M.; Back, K.; Chappell, J.; Noel, J. P. Science 1997, 277, 1815-1820.
(c) Rynkiewicz, M. J.; Cane, D. E.; Christianson, D. W. Proc. Natl. Acad.
Sci. U.S.A. 2001, 98, 13543-13548. (d) Back, K.; Chappell, J. J. Biol. Chem.
1995, 270, 7375-7381. (e) Rynkiewicz, M. J.; Cane, D. E.; Christianson,
D. W. Biochemistry 2002, 41, 1732-1741.
10.1021/jo702303a CCC: $40.75 © 2008 American Chemical Society
Published on Web 02/02/2008
J. Org. Chem. 2008, 73, 1991-1994
1991

SCHEME 2. General Chain-Extension Method and
Possibility for the Chemoselective Reductive Elimination of
Sulfone
SCHEME 3. General Preparation of Polyprenols:
Geranylgeraniol (12a) and Geranylfarnesol (12b)
TABLE 1. Tests for the Chemoselective Reductive Elimination of
the Sulfonyl Group in 6a
reductive desulfonylation without migration of the carbon-
carbon double bond.11 However, Pd(II) activated not only the
benzenesulfonyl group, but also the thiophenyl group in 6a, and
thus hydride eliminated either group indiscriminately to produce
the mixtures of 7a, 8,12 and 9 (entry 2). The dissolving metal
reduction condition utilizing Li in EtNH2 at -78 °C13 was so
strong that both functional groups were eliminated to give rise
to compound 8 exclusively (entry 3). The chemoselective
reductive elimination of the sulfonyl group over the sulfide
group in 6 was not feasible, so the synthetic plan had to be
modified.
It was envisioned that the chemoselective reductive elimina-
tion of the sulfonyl group would be possible under the condition
using Pd(dppe)Cl2/LiBHEt3 if a terminal hydroxyl group was
utilized in place of the sulfide group. A hydroxyl is converted
into an alkoxide, a poor leaving group, under the basic condition
using LiBHEt3, and may survive the reaction condition. A new
scheme has been devised to apply the chemoselective reductive
elimination of sulfonyl groups in the presence of a terminal
hydroxyl group, which would lead to the polyprenol 12 instead
of the polyprenyl sulfone 1 (Scheme 3). The iteration strategy
for the chain-extension of isoprenoids was used again. The
chain-extended, polyprenyl sulfones 4 finally reacted with the
chain-terminating C5 unit 10, tetrahydropyranyl (THP) ether of
(E)-4-bromo-3-methyl-2-buten-1-ol,14 to produce the allylic
alcohols 11 after deprotection of the THP group. The chemose-
lective reductive elimination of the sulfonyl groups using the
above condition worked very well for 11 to give rise to the
all-(E)-polyprenols 12. Neither migration nor E/Z isomerization
of the carbon-carbon double bond was observed during the
entry
reagent
7a (%)
7a′ (%)
8 (%)
9 (%)
1
2
3
Na(Hg), MeOH
Pd(dppe)Cl2, LiBHEt3
Li, EtNH2
34
17
0
33
0
0
0
30
76
0
23
0
4, which may react with the C5 unit 5 again to give rise to the
allylic sulfide 6 containing the internal allylic sulfone moieties.7
The chemoselective reductive elimination of all the benzene-
sulfonyl groups in 6 would produce the polyprenyl sulfide 7,
which would lead to the C5-extended polyprenyl sulfone 1 upon
oxidation of the sulfide group. The success of this approach
depends on the feasibility of the chemoselective reductive
elimination of a sulfonyl group in the presence of a sulfide
group.
Three representative conditions for the reductive desulfony-
lation have been evaluated for 6a (Table 1). Contrary to the
base-promoted elimination of the benzenesulfonyl group in 6a,
which proceeded chemoselectively to produce the allylic sulfide
containing the conjugated triene moiety,8 none of the above
conditions provided a satisfactory result. The relatively mild
condition of using Na(Hg) with NaHPO4 buffer in MeOH at 0
°C produced the required polyprenyl sulfide 7a chemoselec-
tively, which was, however, contaminated by the same amount
of inseparable regioisomeric allylic sulfide 7a′ (entry 1). The
formation of 7a′ under the condition using Na(Hg) was
considered to be inevitable considering the resonance forms of
the intermediate allylic radical species.9
(10) (a) Kotake, H.; Yamamoto, T.; Kinoshita, H. Chem. Lett. 1982,
1331-1334. (b) Hutchins, R. O.; Learn, K. J. Org. Chem. 1982, 47, 4382-
4384.
Palladium(II)-catalyzed, hydride-promoted reductive desulfo-
nylation has been devised to overcome the above regioisomeric
problem in allylic sulfone compounds.10 The combination of
Pd(dppe)Cl2 and LiBHEt3 consistently worked best for the
(11) (a) Mohri, M.; Kinoshita, H.; Inomata, K.; Kotake, H. Chem. Lett.
1985, 451-454. (b) Mohri. M.; Kinoshita, H.; Inomata, K.; Kotake, H.;
Takagaki, H.; Yamazaki, K. Chem. Lett. 1986, 1177-1180. (c) Bouzbouz,
S.; Kirschleger, B. Synlett 1994, 763-764. (d) Eis, K.; Schmalz, H.-G.
Synthesis 1997, 202-206.
(12) Lai, R. K.; Perez-Sala, D.; Canada, F. J.; Rando, R. R. Proc. Natl.
Acad. Sci. U.S.A. 1990, 87, 7673-7677.
(8) Ji, M.; Choi, H.; Jeong, Y. C.; Jin, J.; Baik, W.; Lee, S.; Kim, J. S.;
Park, M.; Koo, S. HelV. Chim. Acta 2003, 86, 2620-2628.
(9) (a) Sato, K.; Inoue, S.; Onishi, A.; Uchida, N.; Minowa, N. J. Chem.
Soc., Perkin I 1981, 761-769. (b) Grieco, P. A.; Masaki, Y. J. Org. Chem.
1974, 39, 2135-2136.
(13) (a) van Tamelen, E. E.; Holton, R. A.; Hopla, R. E.; Konz, W. E.
J. Am. Chem. Soc. 1972, 94, 8228-8229. (b) Torii, S.; Uneyama, K.;
Ichimura, H. J. Org. Chem. 1978, 43, 4680-4682.
(14) Babler, J. H.; Buttner, W. J. Tetrahedron Lett. 1976, 239-242.
1992 J. Org. Chem., Vol. 73, No. 5, 2008

SCHEME 4. Controlled Electrophilic Cyclization of Acyclic Terpenoids Containing the Structurally Rigid Sulfone Moieties
hydrodesulfonylation. Thus, a general synthetic method for the
all-(E)-polyprenols 12 from readily available geranyl sulfone
1a was established. The efficiency of this process has been
demonstrated for the syntheses of all-(E)-geranylgeraniol (12a)15
and all-(E)-geranylfarnesol (12b) in Scheme 3.
The polyprenols 12 were converted to the polyprenyl sulfones
1 by bromination (PBr3) and sulfonylation (PhSO2Na), which
were then applied to the chain-extension process to produce
the substrates 3 for the controlled cyclization reaction (Scheme
4). Farnesyl sulfone 1b (n ) 2) and geranylgeranyl sulfone 1c
(n ) 3) reacted with the C5 unit 5 to generate 13b (93%) and
13c (81%), respectively. The mild oxidation reaction of the
allylic sulfides 13b and 13c utilizing H2O2 and the LiNbMoO6
catalyst provided the corresponding allylic disulfones 3b (92%)
and 3c (75%), respectively.16
In vitro electrophilic cyclizations of acyclic terpenoids require
strongly acidic conditions. Several sulfonic acids including
superacids have been utilized for initiation of the cyclization.17
We decided to use the relatively mild condition of methane-
sulfonic acid (MeSO3H) in i-PrNO2 at room temperature for
the controlled electrophilic cyclization of the polyprenyl com-
pounds 3. The sesquiterpene 3a did not undergo the cyclization
reaction because it contained only one carbon-carbon double
bond far away from the disulfonyl moieties. Instead, the
hydration product 14 (28%) was obtained together with the
recovered starting material (43%). The diterpene 3b and the
higher homologue 3c underwent the electrophilic cyclization
only at the remote carbon-carbon double bonds away from the
disulfone moieties to produce the monocyclic compound 15
(84%, â:R ) 10:1) and the bicyclic compound 16 (83%, â:R )
5.5:1), respectively.18 It is noteworthy that the â-isomers were
obtained as the major products in the controlled cyclization,
while the R-isomers were reported to be the major products for
the cyclization cascades of the polyprenyl sulfones 1,5 which
manifested the thermodynamic stability of each product.
In conclusion, a general and efficient preparation method of
all-(E)-polyprenols 12 starting from readily available geranyl
sulfone was developed. The synthesis in this study highlights
the chain-extension process utilizing the C5 unit 5 and the chain-
termination process that makes use of the C5 unit 10 and the
chemoselective reductive elimination of the sulfonyl groups.
Also demonstrated was the possibility of controlling the
cyclization cascades of acyclic terpenoids under an acidic
condition by inserting the flat and rigid benzenesulfonyl group
into the polyprenyl chains. The sulfone-mediated chain-exten-
sion and controlled cyclization strategy can be usefully applied
to the syntheses of diverse cyclic terpenoid natural products.
Experimental Section
(2E,6E,10E)-5,9-Bis(benzenesulfonyl)-3,7,11,15-tetramethyl-
hexadeca-2,6,10,14-tetraen-1-ol (11a). To a stirred solution of 4a
(1.88 g, 3.87 mmol) in THF (10 mL) was added a 1.6 M solution
of n-BuLi in hexane (3.14 mL, 5.03 mmol) at -78 °C. The mixture
was stirred at -78 °C for 30 min, and a solution of 10 (1.25 g,
5.03 mmol) in THF (4 mL) was added. The reaction mixture was
stirred at -78 °C for 1 h, quenched with 1 M HCl, and extracted
with EtOAc. The organic layer was dried over anhyd Na2SO4,
filtered, and concentrated under reduced pressure. The crude product
was then dissolved in MeOH (20 mL), and p-TsOH (1.27 g, 6.7
mmol) was added. The mixture was stirred for 20 min in a cold
water bath, and then most of the solvent was removed under reduced
pressure. The crude product was diluted with CH2Cl2 and washed
with saturated aqueous NaHCO3 solution. The organic layer was
dried over anhyd Na2SO4, filtered, and concentrated under reduced
pressure. The crude product was purified by SiO2 flash column
chromatography to give 11a (1.63 g, 2.86 mmol) in 74% yield.
Data for 11a (the major stereoisomer from 2:1 mixture): 1H NMR
δ 1.13 (d, J ) 1.3 Hz, 3H), 1.39 (d, J ) 1.1 Hz, 3H), 1.55 (s, 3H),
1.57 (s, 3H), 1.67 (s, 3H), 1.82-2.00 (m, 4H), 2.17-2.35 (m, 2H),
2.72-2.95 (m, 2H), 3.77-3.99 (m, 2H), 4.03 (d, J ) 6.6 Hz, 2H),
4.92 (d, J ) 13.2 Hz, 1H), 4.96 (d, J ) 11.3 Hz, 1H), 4.98 (br s,
1H), 5.36 (t, J ) 6.9 Hz, 1H), 7.46-7.57 (m, 4H), 7.58-7.68 (m,
2H), 7.76-7.84 (m, 4H) ppm; 13C NMR δ 16.0, 16.3, 16.5, 17.6,
25.6, 26.0, 37.2, 37.9, 39.6, 58.9, 62.8, 62.9, 117.1, 119.9, 123.3,
127.6, 128.7, 128.8, 129.0, 129.1, 131.9, 133.2, 133.6, 133.6, 137.2,
137.4, 141.1, 145.4 ppm; IR (KBr) 3522, 2918, 1447, 1304, 1145,
1084 cm-1; HRMS (CI+) calcd for C26H35O2S [C32H43O5S2
(C6H6SO2) - (H2O)] 411.2352, found 411.2358.
-
Geranylgeraniol (12a). To a stirred solution of 11a (420 mg,
0.73 mmol) in THF (2 mL) was added a 1 M solution of LiBHEt3
in THF (7.34 mL, 7.34 mmol). The mixture was stirred at room
temperature for 40 min, and Pd(dppe)Cl2 (130 mg, 0.22 mmol) was
added. The resulting mixture was stirred at room temperature for
1 h, diluted with CH2Cl2, washed with 1 M NaOH, dried over anhyd
Na2SO4, filtered, and concentrated under reduced pressure. The
crude product was purified by SiO2 flash column chromatography
to give 12a (200 mg, 0.69 mmol) in 95% yield.
(15) For another stereoselective chain-extension method for 12a, see:
Jin, Y.; Roberts, F. G.; Coates, R. M. Org. Synth. 2007, 84, 43-57.
(16) Choi, S.; Yang, J.-D.; Ji, M.; Choi, H.; Kee, M.; Ahn, K.-H.; Byeon,
S.-H.; Baik, W.; Koo, S. J. Org. Chem. 2001, 66, 8192-8198.
(17) (a) Vlad, P. F. Pure Appl. Chem. 1993, 65, 1329-1336. (b) Linares-
Palomino, P. J.; Salido, S.; Altarejos, J.; Sa´nchez, A. Tetrahedron Lett.
2003, 44, 6651-6655.
(18) The controlled cyclization of compound 13b also worked to give
the corresponding monocyclization product in 63% yield, which was 21%
lower than that of the cyclization of disulfone 3b, presumably due to
instability of the C-S bond under an acidic condition.
(2E,6E,10E,14E)-5-(Benzenesulfonyl)-3,7,11,15,19-pentameth-
ylicosa-2,6,10,14,18-pentaenyl Phenyl Sulfide (13c). To a stirred
J. Org. Chem, Vol. 73, No. 5, 2008 1993

solution of geranylgeranyl sulfone 1c (2.23 g, 5.37 mmol) in THF
(10 mL) was added a 1.6 M solution of n-BuLi in hexane (4.7 mL,
7.52 mmol) at -78 °C. The mixture was stirred at -78 °C for 1 h,
and a solution of 5 (2.76 g, 10.74 mmol) in THF (5 mL) was added.
The reaction mixture was stirred at -78 °C for 1.5 h, quenched
with 1 M HCl, extracted with EtOAc, dried over anhyd Na2SO4,
filtered, and concentrated under reduced pressure. The crude product
was purified by SiO2 flash column chromatography to give 13c
(2.71 g, 4.58 mmol) in 85% yield. Data for 13c: 1H NMR δ 1.13
(d, J ) 1.3 Hz, 3H), 1.53 (s, 3H), 1.59 (s, 9H), 1.67 (s, 3H), 1.86-
2.13 (m, 12H), 2.31 (dd, J ) 13.4, 11.3 Hz, 1H), 2.90 (br d, J )
13.4 Hz, 1H), 3.47 (d, J ) 7.7 Hz, 2H), 3.87 (ddd, J ) 11.3, 10.5,
3.1 Hz, 1H), 4.88 (d, J ) 10.5 Hz, 1H), 4.99-5.17 (m, 3H), 5.32
(t, J ) 7.7 Hz, 1H), 7.11-7.31 (m, 5H), 7.45-7.55 (m, 2H), 7.56-
7.65 (m, 1H), 7.79-7.88 (m, 2H) ppm; 13C NMR δ 15.9, 15.9,
16.0, 16.3, 17.6, 25.6, 26.2, 26.5, 26.6, 31.8, 37.0, 39.6, 39.6, 39.6,
63.1, 116.7, 123.0, 123.4, 124.0, 124.3, 125.9, 128.6, 128.6, 129.1,
129.4, 131.1, 133.3, 134.5, 134.9, 135.5, 136.4, 137.7, 145.5 ppm;
IR (KBr) 2919, 1447, 1305, 1147, 1086 cm-1; HRMS (CI+) calcd
for C37H51O2S2 591.3330, found 591.3327.
(2E,6E,10E,14E)-1,5-Bis(benzenesulfonyl)-3,7,11,15,19-pen-
tamethylicosa-2,6,10,14,18-pentaene (3c). To a stirred solution of
13c (1.12 g, 1.9 mmol) in MeOH (20 mL) and benzene (2 mL)
were added LiNbMoO6 (10 mg, 0.04 mmol) and 28% aqueous H2O2
solution (1.2 mL, 11.4 mmol) in a cold water bath. The reaction
mixture was stirred for 11 h, and most of the solvent was removed
under reduced pressure. The crude product was diluted with
CH2Cl2, washed with H2O and 1 M HCl, dried over anhyd
Na2SO4, filtered, and concentrated under reduced pressure. The
crude product was purified by SiO2 flash column chromatography
to give 3c (880 mg, 1.42 mmol) in 75% yield. Data for 3c: 1H
NMR δ 1.14 (d, J ) 1.3 Hz, 3H), 1.35 (s, 3H), 1.58 (d, J ) 1.1
Hz, 3H), 1.60 (s, 6H), 1.68 (s, 3H), 1.91-2.01 (m, 8H), 2.01-
2.12 (m, 4H), 2.34 (dd, J ) 13.6, 11.2 Hz, 1H), 2.93 (br d, J )
13.6 Hz, 1H), 3.75 (d, J ) 8.0 Hz, 2H), 3.86 (ddd, J ) 11.2, 10.5,
3.1 Hz, 1H), 4.88 (d, J ) 10.4 Hz, 1H), 5.03 (br s, 1H), 5.09 (t, J
) 6.8 Hz, 2H), 5.18 (t, J ) 8.0 Hz, 1H), 7.49-7.58 (m, 4H), 7.60-
7.68 (m, 2H), 7.80-7.86 (m, 4H) ppm; 13C NMR δ 16.0, 16.0,
16.3, 16.4, 18.9, 25.6, 26.2, 26.5, 26.7, 37.1, 39.8, 39.9, 40.2, 55.8,
62.9, 113.5, 116.5, 123.3, 124.0, 124.3, 128.3, 128.7, 129.0, 129.2,
131.2, 133.6, 133.7, 135.0, 135.7, 137.4, 138.7, 141.4, 146.2 ppm;
IR (KBr) 2918, 1447, 1306, 1147, 1085 cm-1; HRMS (EI+) calcd
for C37H50O4S2 622.3150, found 622.3150.
(2E,6E)-1,5-Bis(benzenesulfonyl)-3,7-dimethyl-9-(2,5,5,8a-tet-
ramethyl-3,4,4a,5,6,7,8,8a-octahydronaphthalenyl)nona-2,6-di-
ene (16). To a stirred solution of 3c (290 mg, 0.47 mmol) in i-PrNO2
(15 mL) was added MeSO3H (0.15 mL, 2.33 mmol). The mixture
was stirred at room temperature for 30 min, quenched with saturated
aqueous NaHCO3 solution, extracted with ether, dried over anhyd
Na2SO4, filtered, and concentrated under reduced pressure. The
crude product was purified by SiO2 flash column chromatography
to give 16 (240 mg, 0.39 mmol) in 83% yield. Data for 16 (â:R )
5.5:1): 1H NMR δ 0.78 (s, 3H), 0.97 (s, 3H), 0.98 (s, 3H), 1.10 (s,
3H), 1.36 (s, 6H), 1.01-2.05 (m, 15H), 2.33 (dd, J ) 13.6, 10.4
Hz, 1H), 2.93 (br d, J ) 13.6 Hz, 1H), 3.75 (d, J ) 7.7 Hz, 2H),
3.77-3.93 (m, 1H), 4.84 (br s, 1H), 5.18 (br s, 1H), 5.31 (br s,
1H; from R-isomer), 7.47-7.58 (m, 4H), 7.59-7.68 (m, 2H), 7.77-
7.87 (m, 4H) ppm; 13C NMR δ 16.1, 16.3, 16.3, 16.4, 19.9, 21.1,
25.1, 27.0, 27.6, 29.2, 33.4, 33.4, 34.3, 34.4, 37.1, 39.8, 40.4, 55.8,
62.9, 113.6, 113.7, 116.1, 116.2, 128.2, 128.7, 129.0, 129.2, 133.6,
137.3, 137.6, 138.8, 141.3, 147.1 ppm; IR (KBr) 2927, 1447, 1306,
1147, 1085 cm-1; HRMS (FAB+) calcd for C37H51O4S2 623.3229,
found 623.3222.
Acknowledgment. This work was supported by the Korea
Research Foundation Grant KRF-2006-312-C00580.
Supporting Information Available: General experimental,
experimental procedures, and data for 7a, 8, 9, 10, 11b, 12b, 13b,
3b, 14, and 15 and 1H/13C NMR spectra. This material is available
free of charge via the Internet at http://pubs.acs.org.
JO702303A
1994 J. Org. Chem., Vol. 73, No. 5, 2008