Probing a biomimetic approach to mycaperoxide B: Hydroperoxidation studies

Article abstract of DOI:10.1055/S-0029-1219152

Hydroperoxidation studies on a series of alkene substrates demonstrate the introduction of the hydroperoxide functional group into the required position for a biosynthetically inspired synthesis of mycaperoxide B. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/S-0029-1219152

LETTER
509
Probing a Biomimetic Approach to Mycaperoxide B:
Hydroperoxidation Studies
Biomimetic
Ap
d
proachtoMy
u
caperoxide
Barda M. P. Silva, Richard J. Pye, Christine Cardin, Laurence M. Harwood*
Department of Chemistry, University of Reading, Whiteknights, Reading RG6 6AH, UK
Fax +44(118)3786121; E-mail: l.m.harwood@reading.ac.uk
Received 13 October 2009
Dedicated to Gerry Pattenden on the occasion of his 70th birthday; an inspiring scientist and a genial companion.
The proposed route would commence with the known de-
calone 5 and an organometallic species derived from 6.
The key step in this sequence is the intramolecular Micha-
el addition of the intermediate 2 to afford the cyclic per-
oxide that could be converted to the desired carboxylic
acid 1.
Abstract: Hydroperoxidation studies on a series of alkene sub-
strates demonstrate the introduction of the hydroperoxide functional
group into the required position for a biosynthetically inspired syn-
thesis of mycaperoxide B.
Key words: hydroperoxidation, cobalt catalyst, mycaperoxide,
marine endoperoxide, Michael addition.
The work described in this communication, following pre-
vious investigations within our group,4 is concerned with
model studies of the Co(II)-catalysed peroxidation of al-
kenes related to the side chain of the putative hydroperox-
idation substrate in order to validate this approach and
establish the scope and limitations of the key hydroperox-
idation step.
Mycaperoxide B (1) is a member of a group of eight struc-
turally related terpene cyclic peroxides isolated from ma-
rine sponges of the genus Mycale. It was found to exhibit
significant cytotoxicity against various cancer cell lines
and antiviral activity.1 The isolation of a hydroperoxide-
containing norsesterterpene endoperoxide from a marine
sponge of the genus Sigmosceptrella has prompted Capon
to propose a biosynthetic pathway for the synthesis of
these norsesterterpene cyclic peroxides that invokes an in-
tramolecular hydroperoxide Michael-type cyclisation.2,3
Our synthetic planning to access the mycaperoxides has
been inspired by Capon’s proposal and is shown in
Scheme 1.3
The method chosen to introduce the hydroperoxide
functionality utilises the methodology developed by
Mukaiyama et al.5 The catalyst Co(modp)2 (modp = 1-
morpholino-5,5-dimethyl-1,2,4-hexanetrione) was select-
ed as the preferred catalyst for these reactions because of
its reported high efficiency in the conversion of olefins
into the corresponding triethylsilyl peroxide derivatives.5–7
OOH
COOH
O
O
COOMe
OH
OH
intramolecular
Michael addition
H
H
2
mycaperoxide B (1)
Wittig reaction
deprotection
OOTES
O
TBDPS
OH
oxidation
OH
OH
Co(II)-catalysed
peroxidation
H
H
4
3
nucleophilic
coupling
O
I
OTBDPS
+
6
H
5
Scheme 1
SYNLETT 2010, No. 4, pp 0509–0513
0
1.
0
3.
2
0
1
0
Advanced online publication: 22.12.2009
DOI: 10.1055/s-0029-1219152; Art ID: D29109ST
© Georg Thieme Verlag Stuttgart · New York

510
E. M. P. Silva et al.
LETTER
Compound 78 (Scheme 2) was chosen as an initial model
system. The hydroperoxidation of 7, using the reaction
conditions described in the literature,9 led to the formation
of two new compounds. Interpretation of the NMR data of
the less polar component isolated led to it being identified
as 9, with the protected peroxide on the most substituted
carbon of the double bond and the primary alcohol also si-
lylated. The 1H NMR spectrum of the more polar compo-
nent exhibited a broad singlet at d = 2.00 ppm
characteristic of a free hydroxyl and examination of the
integration values of the triplet and quartet at d = 0.99 and
0.68 ppm, respectively, revealed that there was only one
triethylsilyl protecting group present. Additionally, 13C
NMR analysis revealed that a signal corresponding to the
resonance of a quaternary carbon at d = 82.8 ppm was
present leading to the conclusion that hydroperoxidation
had occurred and that the expected compound 8 had been
obtained in 43% yield.
S
(ii)
RO
(i)
OH
10 R = H
TBDPSO
S
N
12
(iii)
11 R = TBDPS
S
O
+
TBDPSO
S
N
OR
O2
14 R = H
15 R = THP
13
(iv)
(v)
THPO
OOTES
(vii)
OR
THPO
OH
16 R = TBDPS
17 R = H
18
(vi)
Scheme 3 Reagents and conditions: (i) a. TBDPSCl, imidazole,
DMF, 35 °C; b. 5 h, r.t., 84%; (ii) Mercapto-BT, ADDP, imidazole,
Me3P, THF, r.t., 24 h, 78%; (iii) MCPBA, NaHCO3, CH2Cl2, r.t., 24
h, 86%; (iv) a. 3,4-DHP, PTSA·H2O, CH2Cl2, 0 °C, 2 h; b. NaHCO3,
30 min, 83%; (v) LHMDS, THF, –78 °C, 1.5 h, 91%; (vi) TBAF,
THF, r.t., 1 h, 80%; (vii) Co(modp)2 (0.05 equiv), O2, Et3SiH, 1,2-
DCE, r.t., 2 h, 28%.
OOTES
OOTES
(i)
OH
+
OTES
OH
7
8 (43%)
9 (19%)
Scheme 2 Reagents and conditions: (i) Co(modp)2 (0.05 equiv), O2,
Et3SiH, 1,2-DCE, r.t.
The coupling to form 4 was achieved via in situ organo-
lithium generation by direct treatment of a mixture of 5
and 6, at –100 °C with two equivalents of t-BuLi leading
to the isolation of 4 in 52% yield as a 3:2 mixture of dia-
stereomers (Scheme 4). The 13C NMR data of the decalin
system of the coupled product 4 correlate well with those
described in the literature for mycaperoxide B (1).1 In par-
ticular, the resonance of C-1 (observed at d = 76.9 and
77.1 ppm) for compound 4 compares favourably with that
for the natural product (d = 77.0 ppm). Desilylation of 4
with TBAF furnished the primary alcohol 19 in 91% yield
(6:1 isomeric ratio).
The methodology was next tested on compound 17
(Scheme 3). Compound 17 was prepared in six steps in an
overall yield of 34%. The free hydroxyl group in 11 was
activated and displaced to form a new carbon–sulfur bond
using a Mitsunobu substitution.10 Oxidation of the sulfide
12 to the sulfone 13 was achieved using MCPBA in 90%
yield. Sulfone 13 and ketone 15 were subsequently react-
ed together in a one-pot Julia–Kocienski olefination reac-
tion to furnish alkene 16 as a 1:1 mixture of E- and Z-
isomers.11 Selective TBAF-mediated silyl deprotection of
16 allowed the isolation of a 2:1 mixture of isomeric alco-
hols 17 in 80% yield.
When compound 19 (Scheme 4) was subjected to
hydroperoxidation13 it gave rise to a 30% purified yield of
hydroperoxide 21 as a 1:1 mixture of diastereomers with
12% of unreacted starting material being recovered. Fol-
Following the previously established conditions for the
hydroperoxidation protocol, reaction of unprotected alco-
hol 17 furnished a 1:1 mixture of isomeric triethylsilyl
protected peroxides 18 in a disappointing 28% yield
(Scheme 3), given its structural similarity to 7, although
the reaction again proceeded with high Markovnikov re-
gioselectivity.
O
(ii)
R
+
OTBDPS
H
16 R = OTHP
5
(i)
The synthetic approach to alkene 4, a substrate closer to
that proposed in the synthetic pathway, relied upon selec-
tive delivery of the lithiated species of 6 equatorially onto
the decalone 5 (Scheme 4). Decalone 5 was prepared us-
ing a modified version of the four-step literature proce-
dure starting from commercially available (–)-carvone.12
The synthesis of 1-(tert-butyldiphenylsilyloxy)-6-iodo-3-
methylhex-3-ene (6) was accomplished through conver-
sion of the THP-protected alcohol 16 to iodide 6 using io-
dine and DIPHOS in 75% yield as a 2:1 isomeric mixture
(Scheme 4).
6
R = I
OOTES
1'
OR
OR
3'
OH
OH
1
(iv)
9
5
H
H
20 R = TBDPS, 80%
21 R = H, 30%
4
R = TBDPS
(iii)
19 R = H
Scheme 4 Reagents and conditions: (i) a. I2, DIPHOS, CH2Cl2,
0 °C; b. stirring, r.t., 2 h, 75%; (ii) t-BuLi, Et2O, –100 °C, 1.5 h, 52%;
(iii) TBAF, THF, r.t., 3 h, 91%; (iv) O2, Co(modp)2 (0.05 equiv),
Et3SiH, 1,2-DCE, r.t.
Synlett 2010, No. 4, 509–513 © Thieme Stuttgart · New York

LETTER
Biomimetic Approach to Mycaperoxide B
511
lowing literature precedent that the hydroperoxation may was prepared in four steps in an overall yield of 44%
be improved by protection of hydroxyl groups14 we re- (Scheme 6). Treatment of 24 with 2-mercaptobenzothia-
peated the reaction on substrate 4 which furnished com- zole 25 in the presence of sodium hydride, in anhydrous
pound 20 (R = TBDPS) in an excellent yield of 80% tetrahydrofuran, afforded the desired sulfide 26 in 69%.
(Scheme 4). It is worth noting that this reaction took 5.5 Oxidation of the sulfide 26 to the sulfone 27 was achieved
hours, longer than with the other substrates, but that start- using MCPBA in 90% yield. Sulfone 27 and ketone 15
ing material 4 and product 20 were stable to the peroxida- were subsequently coupled in a one-pot Julia–Kocienski
tion conditions permitting reaction to be run until olefination reaction to furnish alkene 28 as a 2:1 mixture
complete consumption of the starting material.
of E- and Z-isomers, respectively.11 The tetrahydropyran
group in 28 was transformed in one step to the iodide 29
using iodine and DIPHOS in 70% yield as a 2:1 isomeric
mixture. The synthesis of the trityl-protected side-chain
analogue 30 (Scheme 7) was accomplished in six steps
following the same procedure described previously in
Scheme 3 in an overall yield of 38%.
Attempted selective deprotection of the tert-butyldiphe-
nylsilyl-protected alcohol in compound 20 with tetrabuty-
lammonium fluoride led to both silyl protecting groups
being removed and compound 22 was isolated in 86% pu-
rified yield as a 1:1 mixture of diastereomers (Scheme 5).
Although this was not the desired outcome of the depro-
tection reaction, it was decided to attempt the oxidation of Both iodide 29 and 30 were reacted with decalone 5
the primary hydroxyl of 22 using Dess–Martin periodi- (Scheme 7) and subjected to Barbier lithiation conditions.
nane. After workup and purification of the complex reac- Intermediate 31 was obtained as a 2:1 mixture of diastereo-
tion mixture, the major component was isolated and mers in 57% yield while compound 32 was prepared as a
proton and carbon NMR spectroscopic analysis of this 1:1 mixture of diastereomers in 32% yield.
compound showed resonances supporting the formation
When the peroxidation reaction was performed using sub-
of the hemiacetal 23 by spontaneous cyclisation of the in-
strate 31 (Scheme 7), analysis of the 1H NMR spectrum of
termediate hydroperoxy aldehyde in 38% yield
the product enabled the assignment of the structure as 33,
isolated in 55% yield as a 1:1 mixture of diastereomers.
The presence of the triethylsilyl peroxyether was indicat-
ed by the loss of the olefin signal and the presence of a set
(Scheme 5).15 Diagnostic of 23 were the characteristic
hemiacetal proton signal at d = 5.25 ppm and the quater-
nary carbon signal at d = 93.4 ppm. The presence in the
13C NMR spectrum of two signals at d = 80.8 and 80.7
of complex ethyl group signals, integrating to 9 and 6 pro-
ppm revealed that compound 23 was obtained as a mix-
tons. Furthermore, in the 13C NMR spectrum two signals
ture of two diastereomers in a 1:1 ratio.
were present at d = 84.4 and 84.3 ppm corresponding to
Guided by the encouraging result obtained with 4 the resonance of the quaternary carbon connected to the
(Scheme 4) and the unsuccessful selective deprotection of protected peroxide. Subsequently, compound 32
the primary tert-butyldiphenylsilyl alcohol 20 (Scheme 7) was subjected to the same established peroxi-
(Scheme 5), dioxolane-protected aldehyde analogue 29 dation conditions and gave a 16% purified yield of perox-
ide 34 as 1:1 mixture of diastereomers with 17% of
unreacted starting material being recovered. It is proposed
that this low yield is due to steric hindrance to the ap-
proach of the catalyst by the bulky trityl protecting group.
OH
1'
O
OOR1
H
O
6'
OR2
(ii)
OH
OH
The deprotection of the acetal was not attempted by usual
aqueous acid hydrolysis16 due to the presence of the acid-
labile triethylsilylperoxy group. Tanemura et al. reported
in 1992 the successful hydrolysis of several acetals to
their corresponding aldehydes or ketones using catalytic
amounts of 2,3-dichloro-5,6-dicyano-p-benzoquinone
(DDQ) in aqueous acetonitrile under neutral conditions.17
H
H
20 R1 = TES, R2 = TBDPS
23a (6'S)
23b (6'R)
(i)
22 R1 = R2 = H
Scheme 5 Reagents and conditions: (i) TBAF, THF, 2 h, r.t., 86%;
(ii) Dess–Martin periodinane, CH2Cl2, r.t., 3 h, 38%.
S
S
O
(i)
O
H
O
H
O
+
HS
S
N
Br
N
24
25
26
(ii)
O
S
O
H
(iii)
O
O
O
+
R
OTHP
S
N
H
O2
27
15
28 R = OTHP
29 R = I
(iv)
Scheme 6 Reagents and conditions: (i) NaH, THF, overnight, r.t., 69%; (ii) MCPBA, NaHCO3, CH2Cl2, r.t., overnight, 90%; (iii) LHMDS,
THF, –78 °C, 2 h, quant.; (iv) a. I2, DIPHOS, CH2Cl2, 0 °C; b. stirring, r.t., 5 h, 70%.
Synlett 2010, No. 4, 509–513 © Thieme Stuttgart · New York

512
E. M. P. Silva et al.
LETTER
O
OOTES
R
R
H
OH
OH
5
+
(ii)
(i)
I
R
H
H
O
O
O
O
29 R =
31 R =
, 57%
33 R =
, 55%
O
O
30 R = CH2OTr
32 R = CH2OTr, 32%
34 R = CH2OTr, 16%
Scheme 7 Reagents and conditions: (i) t-BuLi, Et2O, –100 °C, 1.5 h; (ii) O2, Co(modp)2 (0.05 equiv), Et3SiH, 1,2-DCE, r.t.
OH
O
H
O
H
TESOO
OH
O
O
O
HOO
OH
O
H
6'
OH
(i)
+
H
H
H
33
35
23a (6'S)
23b (6'R)
(ii)
Scheme 8 Reagents and conditions: (i) DDQ, MeCN–H2O (9:1), r.t., 3 h, 72%; (ii) BiCl3, MeOH, r.t., 40 min, 39% (as a mixture).
It was decided to attempt the hydrolysis of the acetal 33 In conclusion, we have demonstrated that introduction of
using DDQ (Scheme 8). The reaction of compound 33 a triethylsilylperoxy substituent into analogues of a poten-
proceeded smoothly at room temperature in aqueous ace- tial synthetic precursor to the mycaperoxides is dependent
tonitrile to give only one product. Analysis of the 1H NMR on hydroxyl protection and this has led to the successful
spectrum revealed that removal of the triethylsilyl group high yielding synthesis of a triethylsilylperoxide 20. The
had occurred, and the two singlets at d = 9.28 and 9.10 ease of cyclisation of the free hydroperoxy group to form
ppm in a ratio of 1:1 were attributed to the resonances of a cyclic peroxyhemiacetal lends support for the biosyn-
the epimeric hydroperoxides, indicating no stereocontrol thetic proposal and augers well for the proposed synthetic
in the original hydroperoxidation. After purification, approach to mycaperoxide B (1).
compound 35 was isolated in 72% yield.
The deprotection of the acetal 33 was also attempted with
bismuth(III) chloride.18 This reaction led to the formation
of the already known hemiacetal 23 and compound 35,
both obtained as a mixture of diastereomers (Scheme 8).
Crystallisation using a mixture of petroleum ether (30–40
°C) and diethyl ether afforded suitable crystals of single
diastereomer 23a19 and subsequent X-ray crystallographic
analysis confirmed the cyclic peroxyhemiacetal structure
(Figure 1).20 This also allowed unambiguous determina-
tion of the stereochemistry at C-1 with the quaternary al-
cohol being in the correct axial position as required for the
preparation of the natural product.
Acknowledgment
E.M.P.S. is grateful to the Portuguese Foundation for Science and
Technology (ref. SFRH/BD/22683/2005) for a PhD grant. We are
also grateful to EPSRC for funding of the Oxford Gemini S Ultra
Image Plate System.
References and Notes
(1) Tanaka, J.; Higa, T.; Suwanborirux, K.; Kokpol, U.;
Bernardinelli, G.; Jefford, C. W. J. Org. Chem. 1993, 58,
2999.
(2) Ovenden, S. P. B.; Capon, R. J. J. Nat. Prod. 1999, 62, 214.
(3) Capon, R. J. Eur. J. Org. Chem. 2001, 633.
(4) (a) Harwood, L. M.; Robertson, J.; Swallow, S. Synlett 1999,
1359. (b) Harwood, L. M.; Robertson, J.; Swallow, S.
Synlett 1999, 185.
(5) (a) Isayama, S.; Mukaiyama, T. Chem. Lett. 1989, 573.
(b) Isayama, S. Bull. Chem. Soc. Jpn. 1990, 63, 1305.
(6) Kato, K.; Yamada, T.; Takai, T.; Inoki, S.; Isayama, S. Bull.
Chem. Soc. Jpn. 1990, 63, 179.
(7) (a) Tokuyasu, T.; Masuyama, A.; Nojima, M.; McCullough,
K. J.; Kim, H.-S.; Wataya, Y. Tetrahedron 2001, 57, 5979.
(b) Tokuyasu, T.; Kunikawa, S.; Abe, M.; Masuyama, A.;
Nojima, M.; Kim, H.-S.; Begum, K.; Wataya, Y. J. Org.
Chem. 2003, 68, 7361. (c) Wu, J.-M.; Kunikawa, S.;
Figure 1
Synlett 2010, No. 4, 509–513 © Thieme Stuttgart · New York

LETTER
Tokuyasu, T.; Masuyama, A.; Nojima, M.; Kim, H.-S.;
Biomimetic Approach to Mycaperoxide B
513
2¢), 27.6 and 27.5 (C-3), 27.21 and 27.17 (C-5¢), 22.1 (5b-
CH3), 22.0 (3¢-CH3), 21.7 (C-4), 18.7 (C-7), 16.6 and 16.43
(2-CH3), 16.36 and 16.2 (9-CH3), 6.8 [Si(CH2CH3)3], 3.9
[Si(CH2CH3)3]. HRMS (CI): m/z calcd for C27H54O4Si [M]+:
470.3791; found: 470.3800.
Wataya, Y. Tetrahedron 2005, 61, 9961. (d) Oh, C. H.;
Kim, H. J.; Wu, S. H.; Won, H. S. Tetrahedron Lett. 1999,
40, 8391.
(8) Mori, K.; Sugai, T.; Maeda, Y.; Okazaki, T.; Noguchi, T.;
Naito, H. Tetrahedron 1985, 41, 5307.
(9) Ito, T.; Tokuyasu, T.; Masuyama, A.; Nojima, M.;
McCullough, K. J. Tetrahedron 2003, 59, 525.
(14) Xu, X.-X.; Dong, H.-Q. Tetrahedron Lett. 1994, 35, 9429.
(15) (a) Dussault, P.; Sahli, A.; Westermeyer, T. J. Org. Chem.
1993, 58, 5469. (b) Clark, G. R.; Nikaido, M. M.; Fair,
C. K.; Lin, J. J. Org. Chem. 1985, 50, 1994. (c)Schmid, G.;
Hofheinz, W. J. Am. Chem. Soc. 1983, 105, 624.
(16) Green, T. W.; Wuts, P. G. M. In Protective Groups in
Organic Synthesis; Wiley-Interscience: New York, 1981,
188.
(10) Falck, J. R.; Lai, J.-Y.; Cho, S.-D.; Yu, J. Tetrahedron Lett.
1999, 40, 2903.
(11) (a) Bellingham, R.; Jarowicki, K.; Kocienski, P.; Martin, V.
Synthesis 1996, 285. (b) Baudin, J. B.; Hareau, G.; Julia,
S. A.; Ruel, O. Tetrahedron Lett. 1991, 32, 1175.
(c) Baudin, J. B.; Hareau, G.; Julia, S. A.; Ruel, O. Bull. Soc.
Chim. Fr. 1993, 130, 336. (d) Baudin, J. B.; Hareau, G.;
Julia, S. A.; Lorne, R.; Ruel, O. Bull. Soc. Chim. Fr. 1993,
130, 856.
(17) Tanemura, K.; Suzuki, T.; Horaguchi, T. J. Chem. Soc.,
Chem. Commun. 1992, 979.
(18) Sabitha, G.; Babu, R. S.; Reddy, E. V.; Yadav, J. S. Chem.
Lett. 2000, 1074.
(12) Gesson, J. P.; Jacquesy, J. C.; Renoux, B. Tetrahedron 1989,
45, 5853.
(19) 6¢a-[2¢¢-(1a-Hydroxy-9,10-trans-2a,5,5,9b-tetramethyl-
decahydronaphthalen-1-yl)ethyl]-6¢b-methyl-1¢,2¢-
dioxan-3¢b-ol (23a)
(13) Typical Procedure for Hydroperoxidation Reaction
Into a flask flushed with oxygen were added 9,10-trans-1-
[3¢-methylhex-3¢-en-6¢-ol]-2a,5,5,9b-tetramethyldecahydro-
naphthalen-1a-ol (19, 53 mg, 0.16 mmol), bis(5,5-dimethyl-
1-morpholino-1,2,4-hexanetrionato)cobalt(II) (4 mg, 0.008
mmol) and 1,2-DCE (2 mL), and the flask was again charged
with oxygen. Triethylsilane (0.052 mL, 0.32 mmol) and t-
BuOOH (2 drops) were added via a 1.0 mL gas-tight syringe,
and the resulting green solution was stirred vigorously under
an oxygen atmosphere at r.t. After stirring for 2.5 h, the
solvent was evaporated under reduced pressure. The residue
was purified by flash column chromatography on silica.
Elution with hexane–acetone (9:1) gave pure 21 as a
colourless oil (20 mg, 30%). IR (thin film): nmax = 3390,
2929, 2869, 1461, 1375, 1051, 1017, 801, 729 cm–1. 1H
NMR (400 MHz, CDCl3): d = 3.68–3.63 (2 H, m, H-6¢),
1.63–1.25 (20 H, m, H 2,3,4,6,7,8,10 and H-1¢,2¢,4¢,5¢), 1.15
and 1.14 (3 H, s, 3¢-CH3), 0.97 (9 H, t, J = 7.4 Hz,
SiCH2CH3), 0.93 and 0.92 (3 H, s, 9-CH3), 0.858 (3 H, d,
J = 6.4 Hz, 2-CH3), 0.860 (3 H, s, 5a-CH3), 0.83 (3 H, s, 5b-
CH3), 0.67 (6 H, q, J = 7.4 Hz, SiCH2CH3). 13C NMR (100
MHz, CDCl3): d = 84.6 and 84.5 (COOTES), 77.1 (C-1),
63.3 (C-6¢), 46.2 (C-10), 43.5 and 43.4 (C-9), 41.8 and 41.7
(C-6), 36.6 and 36.3 (C-2), 33.8 (5a-CH3), 33.3 (C-5), 32.6
(C-1¢), 32.55 and 32.46 (C-8), 32.2 and 32.0 (C-4¢), 31.5 (C-
Mp (lit.) 49–50 °C. IR (thin film): nmax = 3402, 2930, 2863,
1461, 1451, 1372, 1137, 1088, 989 cm–1. 1H NMR (400
MHz, CDCl3): d = 5.26 (1 H, q, J = 4.0 Hz, H-3¢), 3.04 (1 H,
d, J = 4.0 Hz, OH), 2.07–1.17 (20 H, m, H-4¢,5¢,1¢¢,2¢¢ and H-
2,3,4,6,7,8,10), 1.15 (3 H, s, 6¢-CH3), 0.87 (3 H, d, J = 8.0
Hz, 2-CH3), 0.87 (3 H, s, 5a-CH3), 0.83 (3 H, s, 5b-CH3). 13
C
NMR (100 MHz, CDCl3): d = 96.4 (C-3¢), 80.9 (C-6¢), 77.2
(C-1), 46.3 (C-10), 43.4 (C-9), 41.7 (C-6), 36.5 (C-2), 33.8
(5a-CH3), 33.3 (C-5), 32.1 (C-4¢), 31.9 (C-5¢), 31.4 (C-2¢¢),
27.8 (C-8 and C-3), 25.4 (C-1¢¢), 22.1 (6¢-CH3), 22.03 (5b-
CH3), 21.7 (C-4), 18.7 (C-7), 16.5 (2-CH3), 16.3 (9-CH3).
ESI-HRMS: m/z calcd for C21H38O4Na [M + Na]+: 377.2662;
found: 377.2666.
(20) Crystal Data for 23a
C21H38O4, M = 354.51, centered monoclinic, C2, a = 24.384
(3), b = 7.4398 (12), c = 11.0398 Å, V = 2000.5 (5) Å3,
Z = 4, D = 1.177 g cm–3, F(000) = 784. 2586. Independent
reflections were collected on an Oxford Gemini S Ultra
Image Plate System. The structures was solved by direct
methods and refined on F2 using SHELXL97. Final
R = 0.0487, weighted R = 0.1345. These data can be
obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/
cif quoting deposition no. CCDC 750510.
Synlett 2010, No. 4, 509–513 © Thieme Stuttgart · New York