Natural product synthesis from (8aR)- and (8aS)-bicyclofarnesols: synthesis of (+)-wiedendiol A, (+)-norsesterterpene diene ester and (-)-subersic acid

Article abstract of DOI:10.1016/j.tetasy.2007.07.010

Both enantiomers (8aR)-7 and (8aS)-7 of bicyclofarnesol were synthesized from the enzymatic resolution products (1R,4aR,8aR)-1,2,3,4,4a,5,6,7,8,8a-decahydro-5,5,8a-trimethyl-2-oxo-trans-naphthalene-1-methanol-2-ethylene acetal (8aR)-5 (98% ee) and acetate

Full text of DOI:10.1016/j.tetasy.2007.07.010

Tetrahedron: Asymmetry 18 (2007) 1701–1711
Natural product synthesis from (8aR)- and (8aS)-bicyclofarnesols:
synthesis of (+)-wiedendiol A, (+)-norsesterterpene diene ester and
(ꢀ)-subersic acid
Yuusuke Arima, Masako Kinoshita and Hiroyuki Akita*
School of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan
Received 15 June 2007; accepted 10 July 2007
Abstract—Both enantiomers (8aR)-7 and (8aS)-7 of bicyclofarnesol were synthesized from the enzymatic resolution products
(1R,4aR,8aR)-1,2,3,4,4a,5,6,7,8,8a-decahydro-5,5,8a-trimethyl-2-oxo-trans-naphthalene-1-methanol-2-ethylene acetal (8aR)-5 (98% ee)
and acetate of (1S,4aS,8aS)-1,2,3,4,4a,5,6,7,8,8a-decahydro-5,5,8a-trimethyl-2-oxo-trans-naphthalene-1-methanol-2-ethylene acetal
(8aS)-6 (>99% ee), respectively. The formal synthesis of (+)-wiedendiol 1 was achieved via a coupling reaction of an ate complex derived
from 1,2,4-trimethoxybenzene with allyl bromide (8aS)-8 derived from (8aS)-7. The total synthesis of (+)-norsesterterpene diene ester 2
was achieved, based on the synthesis of (13E,10S)-a,b-unsaturated aldehyde 12, derived from (8aS)-7, followed by the selective construc-
tion of the (3E,5E)-diene moiety including a C(2)-stereogenic centre in (+)-2. The total synthesis of (ꢀ)-subersic acid 3 was carried out
based on a Stille coupling between allyl trifluoroacetate congener 25c, derived from (8aR)-7, corresponding to the diterpene part, and aryl
stannane congener 26 in the presence of Pd catalyst and CuI as an additive.
ꢀ 2007 Elsevier Ltd. All rights reserved.
1. Introduction
was achieved7 by a reported procedure,6 and (8aR)-7 was
obtained from (8aR)-4 by a reported procedure5,6 in 74%
overall yield (three steps). Enantiomer (8aS)-7 was also
obtained from (8aS)-6 in the same way in which (8aR)-7
was prepared from (8aR)-5 (Scheme 1). Herein we report
concise syntheses of (+)-wiedendiol A 1 and (+)-norsester-
terpene diene ester 2 from (8aS)-7, and (ꢀ)-subersic acid (3)
from (8aR)-7.
There are many natural products containing the 2,5,5,8a-
tetramethyl-3,4,4a,5,6,7,8,8a-octahydro-naphthalen-1-yl]-
methylene skeleton. Typical among these are (+)-wieden-
diol A 1,1 (+)-norsesterterpene diene ester 22 (ꢀ)-subersic
acid 33 (Scheme 1). For the synthesis of these compounds,
(8aR)- and (8aS)-bicyclofarnesols 7 are desirable starting
materials. The conversion of the natural product (ꢀ)-scla-
reol to (8aS)-74 and the synthesis of (8aR)-7,5 derived from
(3S)-2,2-dimethyl-3-hydroxy-cyclohexanone, have been
reported. Meanwhile, both (8aR)-7 and (8aS)-7 were
obtained based on the optical resolution of b-keto ester
( )-4 using 1,4-di-O-benzyl-L-threitol as a chiral auxiliary.6
In addition, the lipase-assisted resolution of the racemic
primary alcohol ( )-5, derived from ( )-4, was reported
by us to give (8aS)-acetate 6 (49%, >99% ee) and (8aR)-pri-
mary alcohol 5 (49%, 98% ee).7 This method of enzymatic
resolution was found to be effective, and the E-value was
estimated to be 921. Conversion of (8aR)-5 to (8aR)-4
2. Formal synthesis of (+)-wiedendiol A 1
Wiedendiol A 1, which was isolated from the marine
sponge Xestospongia wiedenmayeri, inhibits cholesteryl
ester transfer protein (CETP). The first synthesis of 1 was
achieved based on the condensation of the drimanic alde-
hyde obtained from (ꢀ)-sclareol with the aryllithium
derived from 3,4-dibenzyloxy anisole.4b A straightforward
synthesis of wiedendiol A analogue 11 from (8aS)-7 is
shown in Scheme 2.
The reaction of an ate complex 10 derived from 1,2,4-tri-
methoxybenzene 9 with allyl bromide (8aS)-8 obtained by
treatment of (8aS)-7 with PBr3 gave the desired product
*
Corresponding author. Tel.: +81 047 472 1805; fax: +81 047 476 6195;
e-mail: akita@phar.toho-u.ac.jp
0957-4166/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2007.07.010

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Y. Arima et al. / Tetrahedron: Asymmetry 18 (2007) 1701–1711
OH
HO
HO
b
a
1
COOMe
8
COOH
OMe
10'S
10R
18S
H
H
H
(+)-Wiedendiol A 1
(+)-Norsesterterpene
(-)-Surbersic acid 3
diene ester 2
OAc
O
OH
COOMe
O
O
isopropenyl acetate
lipase PL-266
8aS
8aR
O
+
O
( )-5
in (i-Pr)2O, 33 °C
H
H
H
( )-4
(8aS)-6
49%, >99% ee
(8aR)-5
49%, 98% ee
OH
COOMe
O
ref. 7
ref. 7
a
8aR
8aR
(8aR)-5
74%
H
H
(8aR)-4
(8aR)-7
OH
COOMe
O
a
8aS
8aS
(8aS)-6
72%
H
H
(8aS)-4
(8aS)-7
Scheme 1. Reagents and conditions: (a) (1) (EtO)2P(O)Cl/NaH/THF; (2) Me2CuLi/Et2O; (3) (iBu)2AIH/toluene.
Br
OMe
a
8aS
(8aS)-7
MeO
H
(8aS)-8
OMe
ref. 8
OMe
(+)-Wiedendiol A 1
OMe
10'S
MeO
MeO
b
H
CuLi
2
(10'S)-11
OMe
OMe
10
56% from (8aS)-7
9
t
Scheme 2. Reagents and conditions: (a) PBr3/pyridine/Et2O; (b) (1) BuLi/TMEDA/Et2O; (2) CuCN.
22
{(100S)-11, ½aꢁD ¼ þ69:7 (c 1.71, CHCl3)} in 56% yield
from (8aS)-7. The spectral data (1H NMR) of synthetic
(100S)-11 was identical to that previously reported.8 The
3. Synthesis of (+)-norsesterterpene diene ester 2
(+)-Norsesterterpene diene ester 2 was originally isolated
from an Australian marine sponge, Latrunculia brevis,
and its structure was determined by detailed spectroscopic
analysis, chemical derivatization and degradation.2 The
synthesis of 2 was achieved by the preparation of the chiral
E,E-diene part corresponding to the side chain of 2 and
specific rotation of synthetic (100S)-11 was in accordance
25
with that of the reported sample {½aꢁD ¼ þ72:0 (c 1.75,
CHCl3)}.8 The synthesis of wiedendiol A 1 from (100S)-
11 has already been achieved based on selective
demethylation.8

Y. Arima et al. / Tetrahedron: Asymmetry 18 (2007) 1701–1711
1703
addition to (ꢀ)-2,5,5,8a-tetramethyl- octahydronaphtha-
len-1-one, derived from (ꢀ)-carvone.9 The retrosynthesis
of (+)-2 is shown in Scheme 3. Our synthetic plan for
(+)-2 is based on synthesis of (13E,10S)-a,b-unsaturated
aldehyde 12, followed by the selective construction of the
(3E,5E)-diene moiety including a C(2)-stereogenic centre
in (+)-2.
followed by reduction with LiBH4 gave (S)-alcohol 19
(98% yield), which was treated with 2-mercaptobenzothiaz-
ole (BTSH) in the presence of Ph3P and diethylazodicarb-
oxylate to provide (S)-sulfide 20a (82% yield). Oxidation
of (S)-20a gave the desired sulfone 13a in 80% yield. Treat-
ment of (S)-19 with 1-phenyl-1H-tetrazole-5-thiol (PTSH)
in the presence of Ph3P and diethylazodicarboxylate
provided the (S)-sulfide 20b (96% yield). Oxidation of
(S)-20b gave the desired sulfone 13b in 59% yield. A modi-
fied Julia coupling of (10S)-12 and 13a in the presence of
lithium bis(trimethylsilyl)amide (LHMDS) gave a 6.2:1
(E:Z) mixture (73% yield) of (3E)-21 and (3Z)-21, while
coupling of (10S)-12 and 13b in the presence of LHMDS
afforded a 11:1 (E:Z) mixture (83% yield) of (3E)-21 and
(3Z)-21. Deprotection of the silyl group in an 11:1 mixture
of (3E)-21 and (3Z)-21 followed by chromatographic sepa-
ration provided the desired alcohol (3E)-22 (81% yield);
this was then subjected to a Dess–Martin oxidation to
give the corresponding aldehyde 23 in 53% yield. Oxida-
tion of 23 in tert-BuOH with NaClO2 in the presence of
2-methyl-2-butene and NaH2PO4 gave carboxylic acid 24,
Treatment of (8aS)-7 with PBr3 followed by acetoacetic
ester synthesis gave methyl ketone (10S)-14 [40% overall
yield from (8aS)-7], which was subjected to a Horner–
Emmons reaction to afford a 7:2 mixture of (13E)- and
(13Z)-a,b-unsaturated esters 15. DIBAL reduction of this
mixture gave a mixture of (13E)- and (13Z)-allylic alcohol
16, which was separated to give (13E)-16 [70% overall yield
from (10S)-14] and (13Z)-16 [20% overall yield from
(10S)-14]. The 13E-geometry of 16 was confirmed by an
NOE enhancement (1.3%) between the C(13)-methyl group
and the C(15)-methylene group. Dess–Martin oxidation of
(13E)-16 afforded the desired aldehyde (10S)-12 in 89%
yield. For selective construction of the (3E,5E)-diene moi-
ety including a C(2) stereogenic centre in (+)-2, a modified
Julia coupling method10 using a chiral sulfone, (S)-13a or
(S)-13b, was thought likely to be effective. Commercially
available methyl (S)-3-hydroxy-2-methylpropionate 17
was used for the synthesis of (S)-13a and (S)-13b as the
starting materials. Silylation {(S)-18, 90% yield} of (S)-17
which was treated with CH2N2 to afford the corresponding
25
methyl ester (+)-2 {½aꢁD ¼ þ12:4 (c 0.55, CHCl3)} in 33%
overall yield. The spectral data (1H and 13C NMR) of syn-
thetic (+)-2 were identical to those previously reported for
(+)-2,2 including the specific rotation {[a]D = +13.3 (c 2.55,
CHCl3)}.2
N
13
CHO
Ar;
Ar;
13a
S
(+)-2
+
(BT)
ArSO2
OTBDPS
13a,b
10S
N
N
N
13b
N
H
(10S)-12
(PT)
Ph
Retrosynthesis of (+)-2
TBDPS; tBuPh2Si-
O
3
R4
R1
a
b
d
10S
10S
(8aS)-7
(10S)-12
i
18S
+
13a,b
H
H
(10S)-14
H
R1 = COOMe (13E)-and (13Z)-(10S)-15
R1 = CH2OH (13E)- and (13Z)-(10S)-16
c
R4 = CH2OTBDPS 21
R4 = CH2OH 22
R4 = CHO 23
R4 = COOH 24
R4 = COOMe (+)-2
j
d
MeOOC
f
OR2
OTBDPS
R3
k
l
R2 = H (S)-17
R2 = TBDPS (S)-18
R3 = OH (S)-19
R3 = SBT 20a or SPT 20b
R3 = SO2BT 13a or SO2PT 13b
g
h
e
Scheme 3. Reagents and conditions: (a) (1) PBr3/pyridine/Et2O; (2) methyl acetoacetate/tBuOK/DMSO; (3) 2 M NaOH/MeOH; (b) (1)
(EtO)2P(O)CH2COOMe/NaH/THF; (c) (1) (iBu)2AIH/toluene; (2) separation (d) Dess–Martin reagent/CH2Cl2; (e) tBuPh2SiCl/imidazole/DMF; (f)
LiBH4; (g) for 20a: BTSH/EtOOC–N@N@COOEt/Ph3P/THF for 20b: PTSH/EtOOC–N@N–COOEt/Ph3P/THF; (h) (NH4)6Mo7O24Æ4H2O/30% H2/
EtOH; (i) (Me3Si)2NꢀLi+ (LHMDS)/THF; (j) (1)tBu4N+Fꢀ(TBAF)/THF; (2) separation; (k) NaClO2/2-methyl-2-butene/NaH2PO4/tBuOH/H2O; (l)
CH2N2/Et2O.

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Y. Arima et al. / Tetrahedron: Asymmetry 18 (2007) 1701–1711
4. Synthesis of (ꢀ)-subersic acid 3
the previously reported aryl bromide congener 27,11 the
synthesis of (10R,13E)-allyl alcohol congener 16 from
(8aR)-7 was carried out in the same way as the preparation
of (10S,13E)-16 from (8aS)-7 (Scheme 3). Treatment of
2711 with tert-BuLi followed by the addition of n-Bu3SnCl
gave the desired stannane congener 26 in 62% yield. A Stille
coupling reaction between (10R)-25a, (10R)-25b or (10R)-
25c and aryl stannane congener 26 in the presence of
Pd catalyst was carried out, and results are shown in
Table 1.
(ꢀ)-Subersic acid 3, which was originally isolated from the
Papua New Guinean sponge Suberea sp., an inhibitor of
human 15-lipoxygenase.3 The structure of (ꢀ)-3 was deter-
mined by extensive NMR analysis, and the (5R,10R)-abso-
lute structure of (ꢀ)-3 was deduced based on the positive
molar rotation of (ꢀ)-3.3 The first synthesis of (ꢀ)-3 was
achieved based on the carbon–carbon bond formation at
the dotted line a (Scheme 1) by coupling of an aryl sulfone
corresponding to the sesquiterpene part and an allyl
bromide corresponding to the side chain in (ꢀ)-3.5 This
synthesis made it possible to determine the absolute struc-
ture of (ꢀ)-3.5 Meanwhile, the synthesis of (+)-3 from the
natural product sclareol was carried out via carbon–carbon
bond formation at the dotted line b (Scheme 1) between an
allyl bromide part, corresponding to the left-hand side of
(ꢀ)-3, and an aryl part.11 Our synthetic plan is shown in
Scheme 4; this also involves carbon–carbon bond forma-
tion at the dotted line b. In this way we attempted to
improve the coupling yield, since the yield in previous
case11 was 26%.
When the three substrates were individually subjected to
Stille coupling using tetrakis(triphenyl-phophine)palla-
dium(0) (Pd(Ph3P)4) or tris(dibenzylideneacetone)dipalla-
dium(0)–chloroform adduct [Pd2(dba)3ÆCHCl3] as a Pd
catalyst, no reaction occurred as shown in entries 1–4
and 6. When the reaction of allyl carbonate 25b and 26
was carried out using Pd2(dba)3ÆCHCl3 and LiCl as an
additive at 100 ꢁC, a 1:1 mixture of the coupled products
(20E)-29 and (20Z)-29 was obtained in 44% overall yield
after deprotection of the tetrahydropyranyl group (entry
5). The E/Z ratio was calculated based on the NMR inte-
grated values of the olefinic proton (d 5.30 (t) and 5.24
(t)). In contrast, when the reaction of allyl trifluoroacetate
25c and 26 was carried out using Pd2(dba)3ÆCHCl3 and CuI
as an additive at rt, a ca. 7:1 mixture [(20E)-29/(20Z)-
In order to carry out a Stille coupling between allyl triflate
(10R)-25a, allyl carbonate (10R)-25b or allyl trifluoroace-
tate (10R)-25c and aryl stannane congener 26, derived from
R5
MOMO
MOMO
f
(-)-3
+
10R
OTHP
OTHP
Bu3Sn
Br
26
27
H
Retrosynthesis of (-)-3
R5 = OSO2CF3 (OTf) (10R)-25a
R5 = OCOOEt (10R)-25b
R5 = OCOCF3 (10R)-25c
O
R5
13
g
a
b
(8aR)-7
10R
10R
H
H
(10R)-14
R5 = OH (10R,13E)-16
c or d or e
R5 = OSO2CF3 (OTf) (10R)-25a
or OCOOEt (10R)-25b or OCOCF3 (10R)-25c
MOMO
2'
MOMO
2'
R7
k
OR6
i
(-)-3
R
R
H
H
R6= THP 28
R6 = H 29
R7= CHO 30
R7 = COOH 31
h
j
Scheme 4. Reagents and conditions: (a) (1) PBr3/pyridine/Et2O; (2) methyl acetoacetate/tBuOK/DMSO; (3) 2 M NaOH/MeOH; (b) (1)
(EtO)2P(O)CH2COOMe/NaH/THF; (2) (iBu)2AIH/toluene; (3) separation; (c) Tf2O/pyridine; (d) ClCOOEt/pyridine; (e) (CF3CO)2O/2,6-lutidine/
CH2Cl2; (f) (1) tBuLi/THF; (2) Bu3SnCl; (g) 26/Pd2(dba)3ÆCHCl3/LiCl/DMF or 26/Pd2(dba)3ÆCHCl3/CuI/DMF; (h) p-TsOH/MeOH or PPTS/MeOH; (i)
MnO2; (j) NaClO2/2-methyl-2-butene/NaH2PO4/tBuOH/H2O; (k) (1) 6 M HCl/THF; (2) separation.

Y. Arima et al. / Tetrahedron: Asymmetry 18 (2007) 1701–1711
1705
Table 1. Stille coupling
Entry
Substrate
Catalyst
Additive
Solvent
Conditions
(20E)-29 and (20Z)-29
yielda (%, E:Z)
1
2
3
4
5
6
7
(10R)-25a
(10R)-25a
(10R)-25b
(10R)-25b
(10R)-25b
(10R)-25c
(10R)-25c
Pd(Ph3P)4
Pd(Ph3P)4
Pd(Ph3P)4
Pd2(dba)3ÆCHCl3
Pd2(dba)3ÆCHCl3
Pd(Ph3P)4
CuI
LiCl
CuI
CuI
LiCl
CuI
CuI
DMF
DMF
DMF
DMF
DMF
DMF
DMF
rt, 7 d
NRb
NR
NR
NR
44 (E:Z = 1:1)
NR
54 (E:Z = 7:1)
40 ꢁC, 4 d
100 ꢁC, 4 d
rt, 6 d
100 ꢁC, 4 h
rt, 24 h
Pd2(dba)3ÆCHCl3
rt, 24 h
a Overall yield from (13E)-16.
b No reaction.
29 = 7:1] of the coupled products was obtained in 54%
overall yield (entry 7). The 20E-geometry of the major
product (20E)-29 was confirmed by NOE enhancement
(4.4%) between the C(30)-methyl group and the C(10)-meth-
ylene group. Stille coupling between the same (E)-allyl
carbonate congener12 as 25b and pyridine-containing
stannane12 in the presence of Pd2(dba)3 and LiCl in
DMF was reported to give a ca. 2.5:1 mixture of the cou-
pled products (E:Z = ꢂ2.5:1), from which the desired
(E)-form was obtained in 55% yield.12 Manganese(IV)
oxide (MnO2) oxidation of this 7:1 mixture gave a ca. 8:1
mixture of the corresponding aldehydes (20E)-30 and
(20Z)-30 in 92% yield. Oxidation of the aldehyde mixture
in tert-BuOH with NaClO2 in the presence of 2-methyl-2-
butene and NaH2PO4 gave a 9:1 mixture of the corre-
sponding carboxylic acids 31 in 53% yield, which was trea-
ted with 6 M aqueous HCl to afford a 9:1 mixture of the
(20E)- and (20Z)-natural products 3. Finally, this mixture
6. Experimental
6.1. Methods and results
All melting points were measured on a Yanaco MP-3S
micro melting point apparatus and are uncorrected. 1H
and 13C NMR spectra were recorded on JEOL AL 400
spectrometer in CDCl3. Carbon substitution degrees were
established by DEPT pulse sequence. The fast atom bom-
bardment mass spectra (FAB MS) were obtained with
JEOL JMS 600H spectrometer. IR spectra were recorded
with a JASCO FT/IR-300 spectrometer. The preparative
HPLC systems were composed of a detector (SPD-M10
AVP (SHIMADZU)) and a pump (PU-980 (JASCO)).
HPLC analysis conditions were as follows; column: YMC
ODS-A (4.6 · 250 mm), solvent: 90% MeOH including
0.06% TFA, flow rate: 1 mL/min. Optical rotations were
measured with a JASCO DIP-370 digital polarimeter. All
evaporations were performed under reduced pressure.
For column chromatography, silica gel (Kieselgel 60) was
employed.
was subjected to preparative HPLC to afford (ꢀ)-3
24
{½aꢁD ¼ ꢀ46:7 (c 0.17, CHCl3)} in 69% yield. The spectral
data (1H and 13C NMR) of synthetic (ꢀ)-3 were identical
to those of the reported compound3 including the specific
22
rotation {½aꢁD ¼ ꢀ46:0 (c 0.5, CHCl3)}.3
6.2. (ꢀ)-[(4aR,8aR)-2,5,5,8a-Tetramethyl-3,4,4a,5,6,7,8,8a-
octahydronaphthalen-1-yl]methanol 7
5. Conclusion
(i) To a suspension of NaH (55% in mineral oil) in THF
(100 mL) was added a solution of (8aR)-4 (11.0 g,
43 mmol) in THF (10 mL) at 0 ꢁC and the reaction mixture
was stirred for 1 h at 80 ꢁC. To the above reaction mixture
was added diethyl chlorophosphate (9.02 g, 52.3 mmol) at
0 ꢁC, and the reaction mixture was stirred for 7 h at rt.
The reaction mixture was diluted with brine and extracted
with Et2O. The organic layer was dried over MgSO4 and
evaporated to give a crude oil, which was chromato-
graphed on silica gel (400 g, n-hexane/AcOEt = 1:1) to give
the reported enol phosphonate (14.89 g, 88%) as a colour-
less oil. ½aꢁD ¼ ꢀ61:0 (c 1.02, CHCl3); H NMR spectra
were identical with those of the reported data.3 (ii) To a
suspension of CuI (22.0 g, 115 mmol) in Et2O (50 mL)
was added dropwise a 1.2 M MeLi in Et2O solution
(193 mL, 231.6 mmol) at ꢀ78 ꢁC and the reaction mixture
was stirred for 30 min at the same temperature. A solution
of the above enol phosphonate (14.89 g) in Et2O (50 mL)
was added dropwise to the above Me2CuLi solution at
Two enantiomers (8aR)-7 and (8aS)-7 of bicyclofarnesol
were synthesized from the enzymatic resolution products
2-ethylene acetal alcohol (8aR)-5 (98% ee) and 2-ethylene
acetal acetate (8aS)-6 (>99% ee), respectively. The formal
synthesis of (+)-wiedendiol 1 was achieved by the coupling
reaction of an ate complex derived from 1,2,4-trimethoxy-
benzene with allyl bromide (8aS)-8 derived from (8aS)-7.
The total synthesis of (+)-norsesterterpene diene ester 2
was achieved based on the synthesis of (13E,10S)-a,b-
unsaturated aldehyde 12, derived from (8aS)-7, followed
by selective construction of the (3E,5E)-diene moiety
including a C(2) stereogenic centre in (+)-2. The total syn-
thesis of (ꢀ)-subersic acid 3 was carried out based on the
Stille coupling between allyl trifluoroacetate congner 25c
derived from (8aR)-7, corresponding to the diterpene part,
and aryl stannane congener 26 in the presence of a Pd cat-
alyst and CuI as an additive.
25
1

1706
Y. Arima et al. / Tetrahedron: Asymmetry 18 (2007) 1701–1711
ꢀ78 ꢁC and the reaction mixture was stirred for 12 h at
0 ꢁC. The reaction mixture was diluted with 10% aqueous
NH4Cl and filtered with the aid of Celite. The filtrate was
extracted with Et2O and dried over MgSO4. Evaporation
of the organic solvent gave a crude oil, which was chro-
matographed on silica gel (200 g, n-hexane/AcOEt = 50:1)
to give the reported a,b-unsaturated ester (8.346 g, 87%) as
a colourless oil. ½aꢁD ¼ ꢀ93:4 (c 1.14, CHCl3); H NMR
spectra were identical with those of the reported data.3
(iii) To a solution of the above a,b-unsaturated ester
(8.346 g, 33.4 mmol) was added 1 M diisobutylaluminium
hydride (Dibal) in toluene solution (80 mL, 80 mmol) at
ꢀ78 ꢁC and the reaction mixture was stirred for 5 h at
the same temperature. MeOH (80 mL) was added to the
reaction mixture at ꢀ20 ꢁC. The reaction mixture was
diluted with 2 M aqueous HCl, extracted with Et2O and
dried over MgSO4. Evaporation of the organic solvent
gave a crude oil, which was chromatographed on silica
MeOH to afford colourless prism (100S)-11. (+)-(100S)-11:
22
mp 53–55 ꢁC, ½aꢁD ¼ þ69:7 (c 1.71, CHCl3); IR (neat):
1
2938, 1591, 1476, 1252, 1095, 719 cmꢀ1; H NMR: d 0.80
(3H, s), 0.85 (3H, s), 0.92 (3H, s), 1.09–1.16 (3H, m),
1.31–1.60 (5H, m), 1.47 (3H, s), 1.88 (1H, br d,
J = 13.5 Hz), 1.99–2.03 (2H, m), 3.37 (1H, d, J = 16 Hz),
3.48 (1H, d, J = 16 Hz), 3.72 (3H, s), 3.72 (3H, s), 3.79
(3H, s), 6.49 (1H, d, J = 9 Hz), 6.67 (1H, d, J = 9 Hz).
13C NMR: d 19.2 (t), 19.2 (t), 20.1 (q), 20.5 (q), 21.8 (q),
23.3 (t), 33.3 (s), 33.5 (q), 34.8 (t), 36.8 (t), 39.6 (s), 41.8
(t), 51.9 (d), 56.0 (q), 56.2 (q), 60.1 (q), 105.6 (d), 109.3
(d), 126.1 (s), 126.4 (s), 138.4 (s), 147.3 (s), 148.3 (s),
152.5 (s). Anal. Calcd for C24H36O3: C, 77.38; H, 9.74.
Found: C, 77.20; H, 9.72.
24
1
6.5. 14,15-Bisnor-[8(9),5S,10S]-labdaen-13-one 14
(i) To a solution of the crude bromide (8aS)-8 (2.56 g)
obtained from (8aS)-cyclofarnesol 7 (2.04 g, 9.17 mmol)
and methyl acetoacetate (5.34 g, 46 mmol) in DMSO
(20 mL) was added tert-BuOK (1.42 g, 13.5 mmol) and
whole mixture was stirred for 12 h at 60 ꢁC. The reaction
mixture was diluted with brine and extracted with Et2O.
The organic layer was dried over MgSO4 and evaporated
to give a residue, which was chromatographed on silica
gel (50 g, n-hexane/AcOEt = 10:1) to give the a-substituted
methyl acetoacetate congener (1.33 g) from n-hexane/
AcOEt = 100:1 elution. (ii) A mixture of the above conge-
ner (1.33 g) and aqueous 2 M NaOH solution (10 mL) was
stirred for 3 h at 100 ꢁC. The reaction mixture was evapo-
rated to give a residue, which was diluted with brine and
extracted with Et2O. The organic layer was dried over
MgSO4 and evaporated to give a residue, which was chro-
matographed on silica gel (50 g, n-hexane/AcOEt = 50:1)
gel (300 g, n-hexane/AcOEt = 20:1) to give the reported
24
(8aR)-cyclofarnesol 7 (7.188 g, 97%). ½aꢁD ¼ ꢀ110:0 (c
1
0.3, CHCl3); H NMR spectra were identical with those
of the reported data.3
6.3. (+)-[(4aS,8aS)-2,5,5,8a-Tetramethyl-3,4,4a,5,6,7,8,8a-
octahydronaphthalen-1-yl]methanol 7
(8aS)-Cyclofarnesol 7 was synthesized from (8aS)-4 in 72%
overall yield in the same way as for preparation of (8aR)-7
24
1
from (8aR)-4. (8aS)-7: ½aꢁD ¼ ꢀ110:0 (c 0.15, CHCl3). H
NMR spectra of (8aS)-7 were identical with those of
(8aR)-7.
6.4. (+)-1,2,4-Trimethoxy-3-[50S,100S,80(90)-drimen-110-
yl]benzene 11
to give a colourless oil (5S,10S)-14 [0.98 g, 40% overall
24
(i) To a solution of (8aS)-cyclofarnesol 7 (0.504 g,
2.26 mmol) and pyridine (0.190 g, 2.4 mmol) in Et2O
(5 mL) was added phosphorus tribromide (PBr3; 0.25 mL,
2.6 mmol) at 0 ꢁC and the reaction mixture was stirred
for 10 min. The reaction mixture was diluted with brine
and extracted with Et2O. The organic layer was dried over
MgSO4 and evaporated to give crude 8 (0.648 g), which
was used for the next reaction without further purification.
(ii) To a solution of 1,2,4-trimethoxybenzene 9 (0.946 g,
5.6 mmol) and TMEDA (5 mL, 33 mmol) in Et2O
(10 mL) was added tert-BuLi (1.64 M in pentane solution,
3.5 mL, 5.7 mmol) at ꢀ78 ꢁC and the reaction mixture was
stirred for 1 h at 0 ꢁC. (iii) To dry CuCN (0.503 g,
5.6 mmol) was added the above lithium anion solution at
0 ꢁC and the reaction mixture was stirred for 1.5 h at room
temperature. A solution of crude 8 in Et2O (10 mL) was
added to the generated ate complex 10 and the whole mix-
ture was stirred for 1.5 h at room temperature. The reac-
tion mixture was diluted with H2O and filtered with the
aid of Celite after which the filtrate was extracted with
Et2O. The organic layer was washed with brine and dried
over MgSO4. Evaporation of the organic solvent gave a
residue, which was chromatographed on silica gel (30 g)
to give bromide 8 (0.120 g, 26% overall yield from (S)-
cyclofarnesol) from n-hexane elution and 11 (0.482 g,
56% overall yield from (S)-cyclofarnesol) from n-hexane/
AcOEt = 100:1 elution. A part of 11 was crystallized from
yield from (8aS)-7]. (5S,10S)-14: ½aꢁD ¼ þ74:3 (c 1.12,
CHCl3); IR (neat): 1715 cmꢀ1; H NMR: d 0.80 (3H, s),
1
0.85 (3H, s), 0.91 (3H, s), 1.04–1.10 (3H, m), 1.34–1.49
(3H, m), 1.50 (3H, s), 1.55–1.65 (2H, m), 1.75 (1H, br d,
J = 11 Hz), 1.89–1.99 (2H, m), 2.01–2.15 (1H, m), 2.10
(3H, s), 2.24–2.30 (1H, m), 2.43–2.49 (2H, m). 13C NMR:
d 19.1 (t), 19.1 (t), 19.5 (q), 20.1 (q), 21.7 (t), 21.8 (q),
29.9 (q), 33.4 (s), 33.4 (q), 33.7 (t), 37.0 (s), 39.2 (s), 41.8
(t), 44.7 (t), 52.0 (d), 126.4 (s), 139.1 (s), 208.6 (s). Anal.
Calcd for C18H30O: C, 82.38; H, 11.52. Found: C, 82.24;
H, 11.63. FAB MS m/z: 285 (M++Na).
6.6. [8(9),5S,10S,13E]-Labdadien-15-ol 16 and
[8(9),5S,10S,13Z]-labdadien-15-ol 16
(i) 55% NaH in oil (0.888 g, 20 mmol) was washed with n-
hexane and methyl diethylphosphonoacetate (5.37 g,
25.6 mmol) was added to a suspension of the above NaH
in THF (80 mL). The reaction mixture was stirred for 1 h
at room temperature and a solution of (5S,10S)-14
(1.24 g, 4.7 mmol) in THF (20 mL) was added to the above
reaction mixture. After the whole mixture was stirred for
12 h at room temperature, it was diluted with brine at
0 ꢁC and extracted with Et2O. The organic layer was dried
over MgSO4 and evaporated to give a residue, which was
chromatographed on silica gel (50 g, n-hexane/AcOEt =
100:1) to give a 7:2 mixture of a,b-unsaturated esters 15

Y. Arima et al. / Tetrahedron: Asymmetry 18 (2007) 1701–1711
1707
(1.49 g) as a colourless oil. (ii) To a solution of the above
mixture (1.49 g) in toluene (30 mL) was added 1 M di-
isobutylaluminium hydride (Dibal) in toluene solution
(15 mL, 15 mmol) at ꢀ78 ꢁC and the mixture was stirred
for 10 min at the same temperature. To a reaction mixture
at ꢀ20 ꢁC was added MeOH (30 mL) and whole mixture
was diluted with 2 M aqueous HCl, extracted with Et2O.
The organic layer was dried over MgSO4 and evaporated
to give a residue, which was chromatographed on silica
gel (50 g, n-hexane/AcOEt = 10:1) to afford (13Z)-16
(0.276 g, 20% overall yield from 14) as a colourless oil
(0.68 g, 10 mmol) at 0 ꢁC and the whole mixture was stirred
for 2 h at rt. The reaction mixture was diluted with brine
and extracted with Et2O. The organic layer was dried over
MgSO4 and evaporated to give a residue, which was chro-
matographed on silica gel (90 g, n-hexane/AcOEt = 50:1)
to give the corresponding silyl ether 18 (2.739 g, 90%).
24
(S)-Silyl ether 18: ½aꢁD ¼ þ17:0 (c 1.31, CHCl3); 1H
NMR: d 1.02 (9H, s), 1.14 (3H, d, J = 7 Hz), 2.67–2.72
(1H, m), 3.67 (3H, s), 3.71 (1H, dd, J = 9.8, 5.8 Hz), 3.81
(1H, dd, J = 9.8, 6.8 Hz), 7.34–7.43 (6H, m), 7.61–7.66
(4H, m). (ii) A mixture of silyl ether (2.685 g, 7.5 mmol)
and LiBH4 (0.804 g, 36 mmol) in THF (30 mL) was stirred
for 6 h at 50 ꢁC. To the reaction mixture was added acetone
(5 mL) at 0 ꢁC and the whole mixture was diluted with
brine and extracted with Et2O. The organic layer was dried
over MgSO4 and evaporated to give a residue, which was
chromatographed on silica gel (60 g, n-hexane/AcOEt =
and (13E)-16 (0.947 g, 70% overall yield from 14) as a col-
23
ourless oil in elution order. (13Z)-16: ½aꢁD ¼ þ71:5 (c 0.99,
CHCl3); IR (neat): 3326, 1666 cmꢀ1; 1H NMR: d 0.81 (3H,
s), 0.87 (3H, s), 0.92 (3H, s), 1.08–1.23 (4H, m), 1.35–1.69
(5H, m), 1.58 (3H, s), 1.77 (3H, s), 1.77–2.10 (7H, m),
4.13 (1H, d, J = 7 Hz), 5.36 (1H, t, J = 7 Hz). 13C NMR:
d 19.1 (t), 19.1 (t), 19.6 (q), 20.2 (q), 21.7 (q), 23.4 (q),
27.0 (t), 32.9 (t), 33.3 (q), 33.3 (s), 33.6 (t), 37.0 (t), 39.0
(s), 41.8 (t), 51.8 (d), 59.3 (t), 123.7 (d), 126.3 (s), 140.2
5:1) to give a colourless oil (S)-19 (2.440 g, 98%). (S)-19:
25
½aꢁD ¼ þ5:2 (c 1.0, CHCl3); 13C NMR: d 13.3, 19.3, 27.0
(3C), 37.4, 67.6, 68.7, 127.6 (4C), 129.6 (2C), 133.0 (2C),
135.0, 135.4 (4C). (iii) To a solution of alcohol (1.0 g,
3.0 mmol) in THF (20 mL) was added Ph3P (0.963 g,
3.7 mmol), 2-mercaptobenzothiazole (BTSH, 0.642 g,
3.8 mmol) and 2.2 M diethylazodicarboxylate in toluene
solution (1.5 mL, 3.3 mmol) at 0 ꢁC and the whole mixture
was stirred for 1 h at rt. The reaction mixture was diluted
with brine and extracted with Et2O. The organic layer
was dried over MgSO4 and evaporated to give a residue,
which was chromatographed on silica gel (50 g, n-hexane/
(s), 140.9 (s). HREI-MS: m/z: calcd for C20H34O,
25
290.2610; found, 290.2611. (13E)-16: ½aꢁD ¼ þ67:8 (c
1.11, CHCl3); IR (neat): 3328, 1665 cmꢀ1 1H NMR: d
;
0.81 (3H, s), 0.86 (3H, s), 0.92 (3H, s), 1.07–1.18 (3H, m),
1.32–1.48 (4H, m), 1.52–1.69 (2H, m), 1.55 (3H, s), 1.69
(3H, s), 1.80 (1H, br d, J = 12.5 Hz), 1.89–2.12 (6H, m),
4.14 (2H, d, J = 7 Hz), 5.41 (1H, br t, J = 7 Hz). 13C
NMR: d 16.5 (q), 19.2 (t), 19.7 (t), 19.7 (t), 20.3 (q), 21.9
(q), 26.9 (t), 33.4 (s), 33.4 (q), 33.8 (t), 37.1 (t), 39.2 (s),
40.3 (t), 41.9 (t), 52.0 (d), 59.5 (t), 122.5 (d), 125.9 (s),
140.0 (s), 140.6 (s). Anal. Calcd for C20H34O: C, 82.69;
H, 11.80. Found: C, 82.25; H, 11.80.
AcOEt = 20:1) to give the corresponding sulfide 20a
22
(1.19 g, 82%) as a colourless oil. Sulfide 20a: ½aꢁD ¼ þ7:3
1
(c 1.05, CHCl3); H NMR: d 1.44 (9H, s), 1.45 (3H, d,
J = 7.8 Hz), 2.52–2.61 (1H, m), 3.64 (1H, dd, J = 13,
7 Hz), 3.95–4.02 (2H, m), 4.04–4.10 (1H, m), 7.61–7.81
(8H, m), 8.02–8.06 (4H, m), 8.10 (1H, dd, J = 7.3,
0.6 Hz), 8.20 (1H, dd, J = 7.3, 0.6 Hz). 13C NMR: d 16.5,
19.5, 27.0 (3C), 36.1, 37.2, 67.2, 120.7, 121.3, 123.9,
125.8, 127.5 (4C), 129.5 (2C), 133.4 (2C), 135.0, 135.4
(4C), 153.1, 167.3. Anal. Calcd for C27H31NOS2Si: C,
67.88; H, 6.54; N, 2.93. Found: C, 67.38; H, 6.53; N,
2.86. FAB MS m/z: 478 (M++1). (iv) To a solution of sul-
fide (20a, 1.21 g, 2.3 mmol) in EtOH (15 mL) was added
Mo7O24(NH4)6Æ4H2O (0.295 g, 0.24 mmol) and 30% H2O2
(1.8 mL) at 0 ꢁC and the whole mixture was stirred for
4 h at room temperature. The reaction mixture was
diluted with 10% aqueous Na2S2O3 and extracted with
Et2O. The organic layer was washed with brine and dried
over MgSO4. The organic layer was evaporated to give a
crude residue, which was chromatographed on silica gel
6.7. [8(9),5S,10S,13E]-Labdadien-15-al 12
To a solution of (13E)-16 (0.284 g, 0.98 mol) in CH2Cl2
(10 mL) was added Dess–Martin periodinane (0.511 g,
1.2 mmol) at 0 ꢁC and the mixture was stirred for 1 h at
the same temperature. The reaction mixture was diluted
with 7% aqueous NaHCO3 and extracted with CH2Cl2.
The organic layer was dried over MgSO4 and evaporated
to give a residue, which was chromatographed on silica
gel (5 g, n-hexane/AcOEt = 20:1) to give (10S,13E)-12
23
(0.253 g, 89%) as a colourless oil. (10S,13E)-12: ½aꢁD
¼
þ66:9 (c 1.08, CHCl3); IR (neat): 1675, 1633 cmꢀ1
;
1H
NMR: d 0.81 (3H, s), 0.86 (3H, s), 0.92 (3H, s), 1.07–1.17
(2H, m), 1.32–1.65 (5H, m), 1.55 (3H, s), 1.77 (1H, br d,
J = 12.5 Hz), 1.90–2.07 (4H, m), 2.12–2.27 (3H, m), 2.17
(3H, s), 5.88 (1H, dt, J = 1, 8 Hz), 9.97 (1H, d,
J = 8 Hz). 13C NMR: d 17.8 (q), 19.2 (t), 19.2 (t), 19.6
(q), 20.3 (q), 21.8 (q), 26.1 (q), 33.4 (q), 33.4 (s), 33.7 (t),
37.1 (t), 39.2 (s), 41.4 (t), 41.8 (t), 51.9 (d), 126.6 (d),
126.8 (s), 139.0 (s), 164.3 (s), 191.0 (d). Anal. Calcd
for C20H32O: C, 83.27; H, 11.18. Found: C, 82.87; H,
11.14.
(30 g, n-hexane/AcOEt = 10:1) to afford 13a (0.959 g,
24
80%) as a colourless oil. Compound 13a: ½aꢁD ¼ þ21:7 (c
0.91, CHCl3); 1H NMR: d 0.98 (9H, s), 1.11 (3H, d,
J = 6.8 Hz), 2.39–2.50 (1H, m), 3.29 (1H, dd, J = 14.5,
8.6 Hz), 3.45 (1H, dd, J = 10, 7 Hz), 3.64 (1H, dd,
J = 10, 5 Hz), 3.93 (1H, dd, J = 14.5, 4 Hz), 7.28–7.40
(6H, m), 7.53–7.63 (6H, m), 7.98–8.00 (1H, m), 8.16–
8.19 (1H, m). 13C NMR: d 16.8, 19.3, 26.9 (3C), 31.7,
57.7, 67.1, 122.2, 125.4, 127.4, 127.5 (4C), 127.8, 129.6
(2C), 133.0 (2C), 135.3 (4C), 136.7, 152.5, 166.2. Anal.
Calcd for C27H31NO3S2Si: C, 63.61; H, 6.13; N, 2.74.
Found: C, 63.09; H, 6.31; N, 2.75. FAB MS m/z: 532
(M++Na).
6.8. (R)-3-Benzothiazolylsulfanyl-1-tert-butyldiphenylsilyl-
oxy-2-methylpropane 13a
(i) To a solution of commercially available (S)-17 (1.0 g,
8.5 mmol) in DMF (20 mL) was added tert-butyliphenyl-
silyl chloride (TBDPSCl, 2.74 g, 10 mmol) and imidazole

1708
Y. Arima et al. / Tetrahedron: Asymmetry 18 (2007) 1701–1711
6.9. (R)-3-(10-Phenyl-10H-tetrazole-50-sulfanyl)-1-tert-butyl-
diphenylsilyloxy-2-methylpropane 13b
NMR: d 15.4 (q), 16.8 (q), 17.0 (q), 19.3 (t), 19.5 (s), 19.7
(q), 20.3 (q), 21.9 (q), 27.0 (q, 3C), 27.1 (t), 33.8 (t), 37.1
(t), 39.2 (s), 39.8 (d), 40.7 (t), 41.9 (t), 52.0 (d), 60.4 (s),
65.9 (t), 68.8 (t), 119.4 (d), 124.0 (d), 124.8 (d), 125.8 (s),
126.3 (d), 127.4 (d, 4C), 129.3 (d), 132.2 (d), 133.9 (s),
134.3 (d), 135.5 (d, 2C), 137.8 (s), 139.7 (s), 140.2 (s).
FAB MS m/z: 583 (M++1).
(i) To a solution of alcohol (S)-19 (1.15 g, 3.5 mmol) in
THF (20 mL) was added Ph3P (1.10 g, 4.2 mmol), 1-phen-
yl-1H-tetrazole-5-thiol (PTSH, 0.750 g, 4.2 mmol) and
2.2 M diethylazodicarboxylate in toluene solution (2 mL,
4.4 mmol) at 0 ꢁC and whole mixture was stirred for 3 h
at rt. The reaction mixture was diluted with 2 M aqueous
NaOH and extracted with Et2O. The organic layer was
washed with brine and dried over MgSO4. Evaporation
of the organic solvent gave a residue, which was chromato-
graphed on silica gel (50 g, n-hexane/AcOEt = 10:1) to af-
6.11. Modified Julia’s coupling of (10S)-12 and 13b:
synthesis of (18S,3E)-21
To a solution of (10S)-12 (0.225 g, 0.78 mmol) and 13b
(0.371 g, 0.71 mmol) in THF (5 ml) was added lithium
bis(trimethylisilyl)amide (1 M solution in THF, 1.5 mL,
1.5 mmol) at ꢀ78 ꢁC under an argon atmosphere and the
whole mixture was stirred for 3 h at the same temperature.
The reaction mixture was diluted with brine and extracted
with Et2O. The organic layer was dried over MgSO4. Evap-
oration of the organic solvent gave a crude product, which
was chromatographed on silica gel (10 g, n-hexane/
AcOEt = 50:1) to give a 11:1 (E:Z) mixture (0.376 g,
83%) of (3E)-21 and (3Z)-21 as a colourless oil.
ford the corresponding sulfide 20b (1.64 g, 96%) as a
23
colourless oil. Sulfide 20b; ½aꢁD ¼ ꢀ2:5 (c 0.82, CHCl3);
1H NMR: d 1.03 (9H, s), 1.06 (3H, d, J = 6.8 Hz), 2.15–
2.23 (1H, m), 3.40–3.59 (3H, m), 3.67 (1H, dd, J = 10.2,
4.8 Hz), 7.31–7.42 (6H, m), 7.51–7.56 (5H, m), 7.61–7.65
(4H, m). 13C NMR: d 16.5, 19.4, 27.0 (3C), 35.6, 36.9,
67.0, 123.7 (2C), 127.5 (4C), 129.5 (2C), 129.6 (2C),
129.8, 133.2, 133.3, 133.6, 135.4 (4C), 154.5. Anal. Calcd
for C27H32N4OSSi: C, 66.35; H, 6.60; N, 11.46. Found:
C, 6.30; H, 6.62; N, 11.33. FAB MS m/z: 489 (M++1).
(ii) To a solution of sulfide (1.23 g, 2.5 mmol) in EtOH
(15 mL) was added Mo7O24(NH4)6Æ4H2O (0.375 g,
0.3 mmol) and 30% H2O2 (1.8 mL) at 0 ꢁC and the whole
mixture was stirred for 4 h at room temperature. The reac-
tion mixture was diluted with 10% aqueous Na2S2O3 and
extracted with Et2O. The organic layer was washed with
brine and dried over MgSO4. The organic layer was evap-
orated to give a crude residue, which was chromatographed
on silica gel (30 g, n-hexane/AcOEt = 15:1) to afford 13b
6.12. Norsesterterpene diene alcohol (18S,3E)-22
To a solution of (18S,3E)-21 (0.375 g, 0.64 mmol) in THF
(5 mL) was added 1 M tetrabutylammonium fluoride
(TBAF) THF solution (1 mL, 1 mmol) at rt, and the whole
mixture was stirred for 1 h at the same temperature. The
reaction mixture was diluted with brine and extracted with
Et2O. The organic layer was dried over MgSO4. Evapora-
tion of the organic solvent gave a crude product, which
was chromatographed on silica gel (10 g, n-hexane/
(0.774 g, 59%) as a colourless oil. Compound 13b:
24
½aꢁD ¼ þ9:2 (c 0.77, CHCl3); 1H NMR: d 1.05 (9H, s),
AcOEt = 10:1) to give (18S,3E)-22 (0.185 g, 81%) as a
24
1.14 (3H, d, J = 6.8 Hz), 2.46–2.55 (1H, m), 3.52 (1H, dd,
J = 10, 6 Hz), 3.56 (1H, dd, J = 14, 8 Hz), 3.72 (1H, dd,
J = 10, 5 Hz), 4.12 (1H, dd, J = 10, 5 Hz), 7.34–7.43 (6H,
m), 7.61–7.67 (9H, m). 13C NMR: d 16.9, 19.4, 26.9 (3C),
31.3, 60.4, 67.0, 125.0 (2C), 127.7 (4C), 129.5 (2C),, 129.7
(2C), 131.3 (2C), 132.9 (2C), 135.4 (4C), 153.8. FAB MS
m/z: 543 (M++Na).
colourless oil. (18S,3E)-22: ½aꢁD ¼ þ82:6 (c 0.65, CHCl3);
1
IR (neat): 3361 cmꢀ1; H NMR: d 0.81 (3H, s), 0.86 (3H,
s), 0.92 (3H, s), 1.01 (3H, d, J = 6.8 Hz), 1.05–1.84 (9H,
m), 1.56 (3H, s), 1.77 (3H, s), 2.38–2.45 (1H, m), 3.39
(1H, dd, J = 10, 8 Hz), 3.50 (1H, dd, J = 10, 6 Hz), 5.41
(1H, d, J = 15, 8 Hz), 5.82 (1H, d, J = 11 Hz), 6.33 (1H,
dd, J = 15, 11 Hz). 13C NMR: d 16.6 (q), 16.7 (q), 19.1
(t), 19.5 (t), 20.1 (t), 21.7 (q), 26.8 (t), 33.3 (s), 33.3 (q),
33.6 (t), 37.0 (t), 39.1 (s), 40.1 (d), 40.5 (t), 41.8 (t), 51.9
(d), 67.4 (t), 123.6 (d), 126.0 (s), 128.0 (d), 133.6 (d),
139.0 (s), 140.2 (s). HREI-MS: calcd for C24H40O,
344.3080; found, 344.3068.
6.10. Modified Julia’s coupling of (10S)-12 and 13a:
synthesis of (18S,3E)-21
To a solution of (10S)-12 (0.251 g, 0.87 mmol) and 13a
(0.460 g, 0.9 mmol) in THF (5 mL) was added lithium
bis(trimethylisilyl)amide (1 M solution in THF, 1.8 mL,
1.8 mmol) at ꢀ78 ꢁC under an argon atmosphere and the
whole mixture was stirred for 1 h at the same temperature.
The reaction mixture was diluted with brine and extracted
with Et2O. The organic layer was dried over MgSO4. Evap-
oration of the organic solvent gave a crude product, which
was chromatographed on silica gel (10 g, n-hexane/
AcOEt = 50:1) to give a 6.2:1 (E:Z) mixture (0.372 g,
73%) of (3E)-21 and (3Z)-21 as a colourless oil. (3E)-21
6.13. (+)-Norsesterterpene diene ester 2
(i) A mixture of (18S,3E)-22 (0.135 g, 0.39 mmol) and
Dess–Martin reagent (0.198 g, 0.47 mmol) in CH2Cl2
(3 mL) was stirred at 0 ꢁC and the reaction mixture was
stirred for 30 min. The reaction mixture was diluted with
10% aqueous Na2CO3 and extracted with Et2O. The organ-
ic layer was washed with brine and dried over MgSO4.
Evaporation of the organic solvent gave a residue, which
was chromatographed on silica gel (15 g, n-hexane/
1
(major product); H NMR: d 0.82 (3H, s), 0.87 (3H, s),
0.93 (3H, s), 1.04 (9H, s), 1.04 (3H, d, J = 6.8 Hz), 1.08–
1.87 (7H, m), 1.57 (3H, s), 1.74 (3H, s), 1.89–2.14 (6H,
m), 2.39–2.47 (1H, m), 3.44–3.58 (2H, m), 5.47 (1H, dd,
J = 15, 7 Hz), 5.78 (1H, d, J = 11 Hz), 6.24 (1H, dd,
J = 15, 11 Hz), 7.33–7.41 (6H, m), 7.64–7.66 (4H, m). 13C
AcOEt = 20:1) to afford aldehyde 23 (0.072 g, 53%). Com-
26
pound 23: ½aꢁD ¼ ꢀ44:3 (c 0.78, CHCl3); IR (KBr):
1
1696 cmꢀ1; H NMR: d 0.81 (3H, s), 0.86 (3H, s), 0.92
(3H, s), 1.21 (3H, d, J = 6.9 Hz), 1.05–1.86 (15H, m),
1.56 (3H, s), 1.78 (3H, s), 5.48 (1H, d, J = 15, 8 Hz), 5.85

Y. Arima et al. / Tetrahedron: Asymmetry 18 (2007) 1701–1711
1709
(1H, d, J = 11 Hz), 6.30 (1H, d, J = 15, 11 Hz), 9.50 (1H,
d, J = 1.6 Hz). 13C NMR: d 13.8 (q), 17.0 (q), 19.2 (t,
2C), 19.7 (q), 20.3 (q), 21.9 (q), 27.0 (t), 33.4 (q), 33.5 (s),
33.8 (t), 37.1 (t), 39.2 (s), 40.6 (t), 41.9 (t), 50.4 (d), 52.0
(d), 123.2 (d), 126.0 (s), 126.3 (d), 130.1 (d), 139.9 (s),
140.5 (s), 201.2 (s). HREI-MS: calcd for C24H38O,
342.2913; found, 342.2918. (ii) To a solution of (18S,3E)-
23 (0.053 g, 0.15 mmol) and 2-methyl-2-butene (6 mL) in
tert-BuOH (2 mL) was added NaClO2 (0.144 g, 1.6 mmol)
and NaH2PO4 (0.115 g, 0.96 mmol) in H2O (0.5 mL) at rt
and the whole mixture was stirred for 30 min at the same
temperature. The reaction mixture was diluted with 2 M
aqueous HCl and extracted with Et2O. The organic layer
was dried over MgSO4. Evaporation of the organic solvent
gave a crude product, which was chromatographed on sil-
ica gel (5 g, n-hexane/AcOEt = 3:1) to give a carboxylic
acid (24, 0.055 g, quantitative yield) as a colourless oil.
(18S,3E)-24. IR (KBr): 3420, 1696 cmꢀ1; HREI-MS: calcd
for C24H38O2, 358.2872; found, 358.2888. (iii) This acid 24
was treated with CH2N2–ether solution to give a crude oil,
which was chromatographed on silica gel (10 g, n-hexane/
brine and dried over MgSO4. Evaporation of the organic
solvent gave a residue, which was chromatographed on
Florisil (20 g, n-hexane/AcOEt = 100:1) to afford 26
(0.698 g, 62%) as
a colourless oil. 26; IR (neat):
1156 cmꢀ1 1H NMR: d 0.86 (9H, t, J = 7.3 Hz), 0.96–
;
1.08 (8H, m), 1.26–1.35 (6H, m), 1.48–1.75 (9H, m),
1.80–1.89 (1H, m), 3.44 (3H, s), 3.51–3.56 (1H, m), 3.90–
3.95 (1H, m), 4.42 (1H, d, J = 11.4 Hz), 4.68–4.69 (1H,
m), 4.71 (1H, d, J = 11.4 Hz), 5.13 (2H, s), 7.02 (1H, d,
J = 8.5 Hz), 7.27 (1H, dd, J = 8.5, 2.2 Hz), 7.34 (1H, d,
J = 2.2 Hz). 13C NMR: d 10.0 (t, 3C), 13.9 (q, 3C), 19.6
(t), 25.7 (t), 27.2 (t), 27.5 (t), 27.8 (t), 29.2 (t), 29.3 (t),
29.4 (t), 30.7 (t), 55.8 (q), 62.3 (t), 68.7 (t), 94.1 (t), 97.5
(d), 111.7 (d), 129.7 (d), 130.4 (s), 131.1 (s), 136.8 (d),
161.1 (s). Anal. Calcd for C26H46O4Sn: C, 57.68; H, 8.56.
Found: C, 57.48; H, 8.86. MALDI-TOF-MS m/z: 541 (M+).
6.17. Reaction of aryl stannane 26 and (10R,13E)-carbonate
25b
(i) A mixture of (10S,13E)-16 (0.195 g, 0.67 mmol) and
ethyl chloroformate (0.364 g, 3.5 mmol) in pyridine
(5 mL) was stirred at 0 ꢁC and the reaction mixture was
stirred for 1 h. The reaction mixture was diluted with 7%
aqueous NaHCO3 and extracted with Et2O. The organic
layer was washed with 2 M aqueous HCl and brine and
dried over MgSO4. Evaporation of the organic solvent gave
a residue, which was chromatographed on silica gel (10 g,
AcOEt = 50:1) to afford (+)-(18S,3E)-2 (0.019 g, 33%) as
25
a colourless oil. (+)-(18S,3E)-2: ½aꢁD ¼ þ12:4 (c 0.55,
1
CHCl3); H NMR: d 0.82 (3H, s), 0.88 (3H, s), 0.94 (3H,
s), 1.12 (1H, dd, J = 12.5, 2 Hz), 1.12–1.20 (2H, m), 1.29
(3H, d, J = 7 Hz), 1.34–1.67 (5H, m), 1.57 (3H, s), 1.78
(3H, d, J = 1 Hz), 1.80–1.85 (1H, m), 1.91–2.13 (6H, m),
3.20 (1H, ddq, J = 1, 7, 8 Hz), 3.68 (3H, s), 5.63 (1H, dd,
J = 15, 8 Hz), 5.84 (1H, d, J = 11 Hz), 6.34 (1H, ddd,
J = 15, 11, 1 Hz). 13C NMR: d 16.9, 17.6, 19.2 (2C), 19.7,
20.2, 21.8, 26.9, 33.4 (2C), 33.7, 37.1, 39.1, 40.6, 41.9,
43.2, 51.9, 52.0, 123.2, 125.9, 127.8, 129.5, 140.0 (2C),
175.0.
n-hexane/AcOEt = 100:1) to afford
a carbonate 25b
(0.217 g, 82%) as a colourless oil. Compound 25b:
25
1
½aꢁD ¼ ꢀ65:1 (c 1.05, CHCl3); IR (neat): 1744 cmꢀ1; H
NMR: d 0.81 (3H, s), 0.86 (3H, s), 0.91 (3H, s), 1.07–1.22
(3H, m), 1.28 (3H, t, J = 7 Hz), 1.35–1.48 (3H, m), 1.52–
1.64 (2H, m), 1.55 (3H, s), 1.72 (3H, d, J = 0.5 Hz), 1.75–
1.82 (1H, m), 1.88–2.12 (6H, m), 4.17 (2H, dd, J = 14,
7 Hz), 4.62 (2H, d, J = 7 Hz), 5.37 (1H, dt, J = 7,
0.5 Hz). 13C NMR: d 14.4 (q), 16.7 (q), 19.2 (t, 2C), 19.6
(q), 20.2 (q), 21.8 (q), 26.7 (t), 33.4 (q), 33.4 (q), 33.8 (t),
33.7 (t), 39.1 (s), 40.2 (t), 41.9 (t), 52.0 (d), 63.8 (t), 64.6
(t), 117.0 (d), 126.0 (s), 139.8 (s), 143.8 (s), 155.0 (s). EI-
MS: m/z 362 (M+) (ii) To a solution of 25b (0.217 g,
0.60 mmol) in DMF (20 mL) was added 26 (0.659 g,
1.2 mmol), tris(dibenzylideneacetone)dipalladium(0)-chlo-
roform adduct [Pd2(dba)3ÆCHCl3, 0.037 g, 0.036 mmol]
and LiCl (0.085 g, 2 mmol) and the reaction mixture was
stirred for 4 h at 100 ꢁC. The reaction mixture was diluted
with H2O and extracted with Et2O. The organic layer was
washed with brine and dried over MgSO4. Evaporation of
the organic solvent gave a crude oil, which was chromato-
graphed on silica gel (25 g, n-hexane/AcOEt = 100:1) to
afford a mixture (0.400 g) of 26 and 28. (iii) To a solution
of the above mixture in MeOH (10 mL) was added p-TsOH
(0.309 g, 1.79 mmol) and the reaction mixture was stirred
for 2 h at rt. The reaction mixture was diluted with H2O
(5 mL) and evaporated under reduced pressure to give a
residue. This residue was diluted with H2O and extracted
with Et2O. The organic layer was washed with brine and
dried over MgSO4. Evaporation of the organic solvent gave
a crude oil, which was chromatographed on silica gel (15 g,
n-hexane/AcOEt = 5:1) to afford a 1:1 mixture (0.117 g,
44% overall yield from (13E)-16) of (20E)-29 and (20Z)-
29. The E/Z ratio was calculated based on the NMR ana-
6.14. 14,15-Bisnor-[8(9),5R,10R]-labdaen-13-one 14
(5R,10R)-Methyl ketone 14 was synthesized from (8aR)-7
in 37% overall yield in the same way as for preparation
24
of (5S,10S)-14 from (8aS)-7. (5R,10R)-14: ½aꢁD ¼ ꢀ82:0
(c 1.11, CHCl3). 1H NMR spectra of (5R,10R)-14 were
identical with those of (5S,10S)-14.
6.15. [8(9),5S,10R,13E]-Labdadien-15-ol 16
(10R,13E)-Allyl alcohol 16 was synthesized from (5R,10R)-
14 in 45% overall yield in the same way as for preparation
25
of (10S,13E)-16 from (5S,10S)-14. (10R,13E)-16: ½aꢁD
¼
1
ꢀ71:2 (c 1.11, CHCl3). H NMR spectra of (10R,13E)-16
were identical with those of (10S,13E)-16.
6.16. Tetrahydropyranyloxy derivative of (3-tributhylstann-
yl-4-methoxymethoxyphenyl)methanol
To a solution of the known aryl bromide congener 2711
(0.694 g, 2.1 mmol) in THF (30 mL) was added 1.6 M
tert-BuLi in pentane solution (2.7 mL, 4.4 mmol) at
ꢀ78 ꢁC and the mixture was stirred for 1 h at ꢀ78 ꢁC. Tri-
butyltin chloride (n-Bu3SnCl 1.77 g, 5.43 mmol) was added
to the above mixture solution at ꢀ78 ꢁC and whole mixture
was stirred for 1 h at ꢀ78 ꢁC. The reaction mixture was
evaporated to a residue, which was diluted with H2O and
extracted with AcOEt. The organic layer was washed with

1710
Y. Arima et al. / Tetrahedron: Asymmetry 18 (2007) 1701–1711
lysis of integrated values due to the olefinic proton (d 5.30
(t) and 5.24 (t)). Physical data of the desired (20E)-29 is
shown in Section 6.19.
6.19. Oxidation of (20E)-29 and (20Z)-29
To a solution of a 7:1 mixture (0.113 g, 0.25 mmol) of
(20E)-29 and (20Z)-29 and in CH2Cl2 (2 mL) was added
MnO2 (0.764 g, 8.8 mmol) at rt and the whole mixture
was stirred for 2 h at the same temperature. The reaction
mixture was filtered with the aid of Celite. The filtrate
was evaporated to give a crude residue, which was chro-
matographed on silica gel (5 g, n-hexane/AcOEt = 50:1)
to give an 8:1 mixture (0.104 g, 92%) of (20E)-30 and
(20Z)-30 as a colourless oil. (20E)-30 (major product): IR
6.18. Reaction of aryl stannane 26 and (10R,13E)-trifluoro-
acetate 25c
(i) To a solution of (10S,13E)-16 (0.204 g, 0.7 mmol) and in
CH2Cl2 (5 mL) was added 2,6-lutidine (0.232 g, 2.2 mmol)
and trifluoroacetic anhydride (TFAA, 0.252 g, 1.2 mmol)
at ꢀ78 ꢁC and the reaction mixture was stirred for 2 h at
the same temperature. The reaction mixture was diluted
with H2O at 0 ꢁC and extracted with CH2Cl2. The organic
layer was washed with 7% aqueous NaHCO3 and dried
over MgSO4. Evaporation of the organic solvent gave a
crude 25c (0.287 g, quantitative yield), which was used
1
(neat): 1692 cmꢀ1; H NMR: d 0.81 (3H, s), 0.86 (3H, s),
0.92 (3H, s), 1.10–1.18 (2H, m), 1.35–1.47 (3H, m), 1.52–
1.64 (3H, m), 1.55 (3H, s), 1.74 (3H, s), 1.78–1.83 (1H,
m), 1.81–2.11 (6H, m), 3.36 (2H, d, J = 7 Hz), 3.47 (3H,
s), 5.27 (2H, s), 5.30 (1H, t, J = 7 Hz), 7.15 (1H, d,
J = 8 Hz), 7.68 (1H, dd, J = 8, 2 Hz), 7.69 (1H, d,
J = 2 Hz), 9.85 (1H, s). 13C NMR: d 16.4 (q), 19.2 (t,
2C), 19.7 (q), 20.3 (q), 21.8 (q), 27.3 (t), 28.7 (t), 33.4 (s),
33.4 (q), 33.7 (t), 37.1 (t), 39.1 (s), 40.6 (t), 41.9 (t), 52.0
(d), 56.3 (q), 93.9 (t), 113.1 (d), 120.5 (d), 125.7 (s), 130.0
(d), 130.3 (s, 2C), 130.8 (d), 131.4 (s), 137.9 (s), 140.2 (s),
191.0 (d). Anal. Calcd for C29H42O3ÆH2O: C, 76.55; H,
9.42. Found: C, 76.27; H, 9.71. EI-MS m/z: 438 (M+).
for the next reaction without further purification. Com-
23
pound 25c: ½aꢁD ¼ ꢀ55:7 (c 1.14, CHCl3); IR (neat):
1
1784 cmꢀ1; H NMR: d 0.82 (3H, s), 0.87 (3H, s), 0.92
(3H, s), 1.09–1.21 (3H, m), 1.38–1.65 (5H, m), 1.58 (3H,
s), 1.61–1.76 (1H, m), 1.55 (3H, s), 1.82 (3H, d,
J = 0.5 Hz), 1.91–2.17 (6H, m), 4.82 (2H, d, J = 7 Hz),
5.36 (1H, dt, J = 7, 0.5 Hz). 13C NMR: d 16.6 (q), 19.1
(t, 2C), 19.5 (q), 20.1 (q), 21.7 (q), 26.5 (t), 33.3 (q), 33.3
(s), 33.6 (t), 37.0 (t), 39.1 (s), 40.2 (t), 41.8 (t), 51.9 (d),
64.9 (t), 115.2 (d), 126.3 (s), 139.8 (s), 146.6 (s), 157.3 (s),
157.8 (s). HREI-MS: calcd for C22F3H33O2, 386.2433;
found, 386.2447. (ii) To a solution of 25c (0.287 g) in
DMF (3 mL) was added 26 (0.495 g, 0.92 mmol),
Pd2(dba)3ÆCHCl3 (0.041 g, 0.04 mmol) and CuI (0.008 g,
0.04 mmol) and the reaction mixture was stirred for 24 h
at rt. The reaction mixture was diluted with H2O and
extracted with AcOEt. The organic layer was washed with
brine and dried over MgSO4. Evaporation of the organic
solvent gave a crude oil, which was chromatographed on
silica gel (30 g, n-hexane/AcOEt = 80:1) to afford a mixture
(0.242 g) of 26 and 28. (iii) To a solution of the above
mixture in MeOH (5 mL) was added pyridinium p-toluene-
sulfonate (PPTS, 0.105 g, 0.4 mmol) and the reaction
mixture was stirred for 8 h at rt. The reaction mixture
was diluted with H2O and extracted with Et2O. The organ-
ic layer was washed with 7% aqueous NaHCO3 and dried
over MgSO4. Evaporation of the organic solvent gave a
crude oil, which was chromatographed on silica gel (25 g,
n-hexane/AcOEt = 10:1) to afford a 7:1 mixture [0.168 g,
54% overall yield from (13E)-16] of (20E)-29 and (20Z)-
29. The E/Z ratio was calculated based on the NMR anal-
ysis of integrated values due to the olefinic proton (d 5.30
(t) and 5.24 (t)). (20E)-29 (major product): IR (neat):
6.20. (ꢀ)-Subersic acid 3
(i) To a solution of a 8:1 mixture (0.122 g, 0.28 mmol) of
(20E)-30 and (20Z)-30 and 2-methyl-2-butene (4 mL) in
tert-BuOH (2 mL) was added NaClO2 (0.263 g, 2.9 mmol)
and NaH2PO4 (0.212 g, 1.8 mmol) in H2O (1 mL) at rt
and the whole mixture was stirred for 3 h at the same
temperature. The reaction mixture was diluted with 2 M
aqueous HCl and extracted with Et2O. The organic layer
was dried over MgSO4. Evaporation of the organic solvent
gave a crude product, which was chromatographed on
silica gel (5 g, n-hexane/AcOEt = 10:1) to give a 9:1 mix-
ture (0.068 g, 53%) of (20E)-31 and (20Z)-31 as a colourless
oil. Major (20E)-31: IR (neat): 1686 cmꢀ1; 1H NMR: d 0.81
(3H, s), 0.86 (3H, s), 0.92 (3H, s), 1.08–1.20 (2H, m), 1.33–
1.48 (3H, m), 1.52–1.59 (3H, m), 1.55 (3H, s), 1.74 (3H, s),
1.78–1.83 (1H, m), 1.88–2.14 (6H, m), 3.35 (2H, d,
J = 7 Hz), 3.46 (3H, s), 5.26 (2H, s), 5.30 (1H, t,
J = 7 Hz), 7.08 (1H, d, J = 8 Hz), 7.90 (1H, d, J =
2.3 Hz), 7.91 (1H, dd, J = 8, 2.3 Hz). 13C NMR: d 16.4
(q), 19.2 (t, 2C), 19.7 (q), 20.2 (q), 21.9 (q), 27.3 (t), 28.7
(t), 33.4 (s), 33.5 (q), 33.7 (t), 37.1 (t), 39.1 (s), 40.6 (t),
41.9 (t), 52.0 (d), 56.2 (q), 93.9 (t), 112.7 (d), 120.9 (d),
121.1 (s), 125.7 (s), 129.8 (s), 130.7 (s), 131.7 (d), 137.6
(s), 140.3 (s), 159.1 (s), 171.0 (s). HREI-MS: calcd for
C29H42O4, 454.3078; found, 454.3083. (ii) To a solution
of a 9:1 mixture (0.063 g, 0.14 mmol) of (20E)-31 and
(20Z)-31 in THF (5 mL) was added 6 M aqueous HCl
(3 mL) at rt and the whole mixture was stirred for 3 h at
40 ꢁC. The reaction mixture was diluted with H2O and
extracted with AcOEt. The organic layer was washed with
brine and dried over MgSO4. Evaporation of the organic
solvent gave a crude product, which was chromatographed
on silica gel (15 g, n-hexane/AcOEt = 1:1) to give a carbox-
ylic acid. This crude carboxylic acid was subjected to
1
3382 cmꢀ1; H NMR: d 0.81 (3H, s), 0.86 (3H, s), 0.91
(3H, s), 1.07–1.16 (2H, m), 1.35–1.46 (3H, m), 1.55 (3H,
s), 1.58–1.64 (3H, m), 1.73 (3H, s), 1.75–1.81 (1H, m),
1.88–2.12 (6H, m), 3.33 (2H, d, J = 7 Hz), 3.45 (3H, s),
4.58 (2H, s), 5.18 (2H, s), 5.29 (1H, t, J = 7 Hz), 7.02
(1H, d, J = 8 Hz), 7.13 (1H, dd, J = 8, 2 Hz), 7.14 (1H,
d, J = 2 Hz), 9.85 (1H, s). 13C NMR: d 16.2 (q), 19.1 (t,
2C), 19.6 (q), 20.2 (q), 21.7 (q), 28.6 (t), 29.3 (t), 33.3 (s),
33.3 (q), 33.6 (t), 37.0 (t), 39.0 (s), 40.5 (t), 41.8 (t), 51.9
(d), 55.9 (q), 65.2 (t), 94.2 (t), 113.9 (d), 121.6 (d), 125.7
(s), 125.8 (d), 128.7 (d), 128.8 (d), 131.1 (s), 134.0 (s),
137.1 (s), 140.5 (s), 154.4 (s). HREI-MS: calcd for
C29H44O3, 440.3291; found, 440.3296.
preparative HPLC to afford (ꢀ)-3 (0.040 g, 69%) as a col-
24
ourless amorphous solid. Compound (ꢀ)-3: ½aꢁD ¼ ꢀ46:7

Y. Arima et al. / Tetrahedron: Asymmetry 18 (2007) 1701–1711
1711
(c 0.17, CHCl3); IR (neat): 3280 (br), 1682, 1600 cmꢀ1; H
NMR: d 0.81 (3H, s), 0.86 (3H, s), 0.92 (3H, s), 1.08–1.26
(3H, m), 1.32–1.48 (3H, m), 1.53–1.64 (3H, m), 1.55 (3H,
s), 1.80 (3H, s), 1.88–2.12 (6H, m), 3.40 (2H, d,
J = 7 Hz), 5.33 (1H, t, J = 7 Hz), 6.84 (1H, d, J = 9 Hz),
7.88 (1H, dd, J = 9, 1.8 Hz), 7.89 (1H, d, J = 1.8 Hz). 13C
NMR: d 16.5 (q), 19.2 (t, 2C), 19.7 (q), 20.3 (q), 21.8 (q),
27.2 (t), 29.7 (t), 29.8 (t), 33.4 (q), 33.7 (t), 37.1 (t), 39.1
(s), 40.5 (t), 41.9 (t), 51.9 (d), 113.6 (d), 120.0 (d), 121.5
(s), 125.9 (s), 126.7 (s), 130.4 (d), 132.4 (d), 139.9 (s),
140.4 (s), 159.3 (s), 171.6 (s). Anal. Calcd for C27H38O3Æ
2H2O: C, 72.61; H, 9.48. Found: C, 72.88; H, 9.22. EI-
MS m/z: 410 (M+).
1
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Acknowledgement
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The authors are grateful to Professor Kazuo Koike at
Toho University in Japan for preparative HPLC separa-
tion of the synthetic (ꢀ)-subersic acid in his laboratory.
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References
1. Coval, S. J.; Conover, M. A.; Mierzwa, R.; King, A.; Puar,
M. S.; Phife, D. W.; Pai, J.-K.; Burrier, R. E.; Ahn, H.-S.;