Enantioselective synthesis of valoneic acid derivative

Article abstract of DOI:10.1016/j.tetlet.2007.11.154

The enantioselective synthesis of trimethyl octa-O-methylvaloneate (1) was accomplished using the Bringmann's 'lactone concept', which involves the intramolecular biaryl coupling reaction of a phenyl benzoate derivative and the asymmetric lactone-opening

Full text of DOI:10.1016/j.tetlet.2007.11.154

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 605–609
Enantioselective synthesis of valoneic acid derivative
Hitoshi Abe a,b,*, Yusuke Sahara a, Yuki Matsuzaki a, Yasuo Takeuchi a, Takashi Harayama c
a Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan
b Advanced Science Research Center, Okayama University, Okayama 700-8530, Japan
c Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, Sanuki, Kagawa 769-2193, Japan
Received 18 September 2007; revised 17 November 2007; accepted 27 November 2007
Available online 3 December 2007
Abstract
The enantioselective synthesis of trimethyl octa-O-methylvaloneate (1) was accomplished using the Bringmann’s ‘lactone concept’,
which involves the intramolecular biaryl coupling reaction of a phenyl benzoate derivative and the asymmetric lactone-opening reaction.
Ó 2007 Elsevier Ltd. All rights reserved.
Ellagitannins are natural polyphenolic compounds,
which are widely distributed in many kinds of higher
plants.1 Because of their interesting biological activities
based on an antioxidant property, this class of compounds
has been expected for medicinal use.2 A valoneoyl group is
commonly observed in some class of ellagitannins, espe-
cially in its oligomers. Typical examples of some ellagitan-
nins, which possess the valoneoyl group in the molecule,
are shown in Figure 1.3 In the course of the studies for
structure determination, trimethyl octamethylvaloneate
(1) has often been isolated during experiments involving
the solvolysis and methylation process.4 To date, the syn-
thesis of 1 has never been performed, although it is an
important part structure of ellagitannin family.5
In this Letter, we describe the enantioselective synthesis
of the valoneic acid derivative, trimethyl octamethylvalon-
eate (1).
The synthetic plan is outlined in Scheme 1. Since we
envisioned that Bringmann’s ‘lactone concept’ would be a
useful method6 for the construction of the axially chiral
biphenyl moiety, lactone 2 should be a key intermediate
in this synthesis. As an appropriate precursor of lactone
2, ester 3 should be realized by a simple esterification
between the corresponding phenol 4 and carboxylic acid
5. Phenol 4 was expected to be prepared by the Ullmann
type coupling7 between phenol 68 and bromide 7.9
Based on the above synthetic plan, we initially prepared
ester 3 as depicted in Scheme 2. The Ullmann coupling of
phenol 6,8 which was easily prepared by the reported
method, and bromide 79 produced the desired biphenyl
ether 8. The deprotection under hydrogenolysis conditions
led to phenol 4, which was coupled with benzoic acid 510
using EDC.
Unfortunately, all attempts for the intramolecular biaryl
coupling reaction11 of 3 were unsuccessful. This result is
similar to the previously reported ones,11b in which the
neighboring ester group to the reacting position gives a
negative effect in the Pd-mediated biaryl coupling reaction.
Thus, we thought that the ester groups should be con-
verted into a protected carbinol function such as the acet-
oxymethyl group (Scheme 3). Two ester groups in 8 were
reduced with LiAlH4 to afford bisalcohol 9, followed by
acetylation. The debenzylation of 10 was carried out to
form phenol 11, which was coupled with 510 using the usual
esterification process.
Scheme 4 demonstrates the transformation of ester 12
into the axially chiral biphenyl derivative 15 using Bring-
mann’s ‘lactone concept’. The intramolecular biaryl cou-
pling reaction using Pd(OAc)2, Ph3P, and NaOAc
successfully produced lactone 13. In the next step for the
lactone-opening reaction of 13, the combination of the
borane and chiral oxazaborolidine (CBS reagent, 14)12
*
Corresponding author. Tel.: +81 862517965; fax: +81 862517926.
E-mail address: abe@pharm.okayama-u.ac.jp (H. Abe).
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.11.154

606
H. Abe et al. / Tetrahedron Letters 49 (2008) 605–609
OH
HO
OH
HO
OH
O
HO
OH
OH
OH
HO
HO
CO O
CO O
CO O
O
O
O
O G
HO
HO
HO
HO
CO O
OH
OH
O
G
O
C
G
O
HO
HO
HO
O
O
O
HO
O
C
O
CO2H
O
CO
OC
O
OH
OH
OH
OH
O
G
G =
CO
OH
OH
OH
OH
OH
Oenothein B
OMe
Isorugosin B
OH
HO
MeO
HO
HO
CO
CO
MeO
MeO
CO2Me
CO2Me
HO
HO
HO
MeO
MeO
MeO
O
O
CO
CO2Me
OH
OMe
Valoneoyl group
Trimethyl octa-O-methylvaloneate
(1)
Fig. 1. Examples of valoneoyl group-containing ellagitannins.
OMe
OMe
OMe
X
MeO
OMe
OMe
O
O
MeO
MeO
CO2Me
CO2Me
Bringmann's
method
OMe
CO2Me
[Pd]
OMe
O
O
CO2Me
MeO
MeO
MeO
MeO
MeO
MeO
O
O
MeO
MeO
MeO
CO2Me
CO2Me
O
CO2Me
OMe
OMe
OMe
2
1
3
BnO
MeO
CO2Me
OMe
X
HO
CO2Me
OMe
OMe
OH
+
6
+
MeO
MeO
MeO
HOOC
O
Br
CO2Me
MeO
MeO
CO2Me
5
OMe
7
OMe
4
Scheme 1. Synthetic outline of 1.

H. Abe et al. / Tetrahedron Letters 49 (2008) 605–609
607
BnO
CO2Me
CO2Me
Br
H2, Pd-C
MeOH
BnO
MeO
CO2Me
MeO
MeO
CO2Me
Cu
MeO
MeO
MeO
+
O
56%
81%
OH
OMe
6
7
OMe
8
OMe
I
HO
CO2Me
CO2Me
OMe
OMe
OMe
OMe
O
MeO
MeO
MeO
O
HOOC
OMe
O
MeO
MeO
MeO
CO2Me
I
5
EDC, DMAP, CH2Cl2
98%
OMe
O
CO2Me
4
OMe
3
Scheme 2. Synthesis of ester 3.
BnO
OR
HO
MeO
MeO
MeO
BnO
CO2Me
OAc
LiAlH4
THF
H2, Pd-C
MeOH
MeO
MeO
MeO
MeO
MeO
MeO
O
O
O
93%
CO2Me
89%
OR
OAc
OMe
OMe
OMe
8
9: R = H
10: R = Ac
Ac2O, pyr.
89%
11
OMe
OMe
OMe
OMe
OMe
O
HOOC
OMe
I
I
O
5
OAc
MeO
MeO
MeO
EDC, DMAP, CH2Cl2
94%
O
OAc
12
OMe
Scheme 3. Synthesis of ester 12.
succeeded in the generation of the optically active (S)-15 in
an enantiomerically pure form.13
compound was determined by the comparison of the
optical rotation sign with the reported data.14
In conclusion, we synthesized the valoneic acid
derivative (S)-1, an important part of the structure of the
ellagitannins. Further transformation toward natural
ellagitannins, involving manipulation of the protecting
groups on phenolic OH, is now underway in our
laboratory.
The phenolic hydroxyl group of (S)-15 was methylated,
and successive reduction of the two acetoxy groups
produced triol (S)-17. Finally, the two-step oxidation of
three hydroxyl groups and the methylation of the generat-
ing carboxylic acids led to the complete synthesis of (S)-1
(Scheme 5). The absolute configuration of the synthetic

608
H. Abe et al. / Tetrahedron Letters 49 (2008) 605–609
OMe
OMe
OMe
OMe
Pd(OAc)2 (25% mol)
Ph3P (50% mol)
NaOAc (200% mol)
DMA
OMe
OMe
O
O
I
O
O
OAc
OAc
MeO
MeO
MeO
MeO
MeO
MeO
64%
O
O
OAc
OAc
12
OMe
13
OMe
OMe
MeO
Ph
H
Ph
OH
MeO
HO
O
N
B
OAc
BH3,
14
Me
MeO
MeO
MeO
THF
84%, 99%ee
O
OAc
15
OMe
Scheme 4. Construction of axially chiral biphenyl compound 15 by Bringmann’s method.
OMe
OMe
OMe
MeO
MeO
MeO
OH
OH
OH
OH
MeO
MeO
MeO
HO
MeO
MeO
MeI, tBuOK
THF
LiAlH4
THF
OAc
OAc
MeO
MeO
MeO
MeO
MeO
MeO
MeO
MeO
MeO
O
quant.
O
O
51%
OAc
OAc
OH
OMe
OMe
OMe
(S)-16
(S)-15
(S)-17
OMe
MeO
1) Jones reagent
acetone
MeO
MeO
CO2Me
CO2Me
2) H2O2, NaClO2, NaH2PO4
MeCN/H2O
3) TMSCHN2
MeOH
MeO
MeO
MeO
O
CO2Me
37%
OMe
(
S)-1
Scheme 5. Synthesis of (S)-1.

H. Abe et al. / Tetrahedron Letters 49 (2008) 605–609
609
Tokumaru, G.; Tsuchiya, H.; Yamada, H. Tetrahedron Lett. 2004,
45, 487–489.
Acknowledgments
6. For recent reviews, see: (a) Bringmann, G.; Breuning, M.; Tasler, S.
Synthesis 1999, 525–558; (b) Bringmann, G.; Menche, D. Acc. Chem.
Res. 2001, 34, 615–624; (c) Bringmann, G.; Breuning, M.; Pfeifer,
R.-M.; Schenk, W. A.; Kamikawa, K.; Uemura, M. J. Organomet.
Chem. 2002, 661, 31–47; (d) Bringmann, G.; Tasler, S.; Pfeifer, R. M.;
Breuning, M. J. Organomet. Chem. 2002, 661, 49–65; (e) Bringmann,
G.; Mortimer, A. J. P.; Keller, P. A.; Gresser, M. J.; Garner, J.;
Breuning, M. Angew. Chem., Int. Ed. 2005, 44, 5384–5427.
7. Lin, J.-H.; Ishimatsu, M.; Tanaka, T.; Nonaka, G.; Nishioka, I.
Chem. Pharm. Bull. 1990, 38, 1844–1851.
The authors are indebted to Professor T. Hatano and
Dr. H. Ito (Okayama University) for providing the authen-
tic sample of 1. We thank the SC-NMR Laboratory of
Okayama University for the use of their facilities. Part of
this work was supported by the Japan Society for the Pro-
motion of Science for H.A. (Grant No. 18590005).
References and notes
8. Tanaka, M.; Ikeya, Y.; Mitsuhashi, H.; Maruno, M.; Wakamatsu, T.
Tetrahedron 1995, 51, 11703–11724.
9. Horning, E. C.; Parker, J. A. J. Am. Chem. Soc. 1952, 2107–2108.
10. Molander, G. A.; George, K. M.; Monovich, L. G. J. Org. Chem.
2003, 68, 9533–9540.
11. (a) Harayama, T. Heterocycles 2005, 65, 697–713; (b) Takeda, S.;
Abe, H.; Takeuchi, Y.; Harayama, T. Tetrahedron 2007, 63, 396–
408; (c) Abe, H.; Nishioka, K.; Takeda, S.; Arai, M.; Takeuchi, Y.;
Harayama, T. Tetrahedron Lett. 2005, 3197–3200; (d) Abe, H.;
Fukumoto, T.; Takeuchi, Y.; Harayama, T. Heterocycles, 74, in press.
1. (a) Yoshida, T.; Hatano, T.; Ito, H. J. Synth. Org. Chem. Jpn. 2004,
62, 500–507; and references cited therein; (b) Okuda, T.; Yoshida, T.;
Hatano, T. In Progress in the Chemistry of Organic Natural Products;
Herz, W., Kirby, G. W., Moore, R. E., Steglich, W., Tamm, C., Eds.;
Springer: Wein, 1995; Vol. 66, pp 1–117.
2. For examples: (a) Miyamoto, K.; Nomura, M.; Murayama, T.;
Furukawa, T.; Hatano, T.; Yoshida, T.; Koshiura, R.; Okuda, T.
Biol. Pharm. Bull. 1993, 16, 379–387; (b) Aoki, K.; Nishimura, K.;
Abe, H.; Maruta, H.; Sakagami, H.; Hatano, T.; Okuda, T.; Yoshida,
T.; Tsai, Y. J.; Uchiumi, F.; Tanuma, S. Biochem. Biophys. Acta 1993,
1158, 251–256; (c) Okuda, T.; Kimura, Y.; Yoshida, T.; Hatano, T.;
Okuda, H.; Arichi, S. Chem. Pharm. Bull. 1983, 31, 1625–1631.
3. (a) Hatano, T.; Kira, R.; Yasuhara, T.; Okuda, T. Chem. Pharm. Bull.
1988, 36, 3920–3927; (b) Hatano, T.; Kira, R.; Yasuhara, T.; Okuda,
T. Heterocycles 1988, 27, 2081–2085; (c) Hatano, T.; Yasuhara, T.;
Matsuda, M.; Yazaki, K.; Yoshida, T.; Okuda, T. Chem. Pharm. Bull.
1989, 37, 2269–2271; (d) Hatano, T.; Ogawa, N.; Kira, R.; Yasuhara,
T.; Okuda, T. Chem. Pharm. Bull. 1989, 37, 2083–2090; (e) Hatano,
T.; Yasuhara, T.; Matsuda, M.; Yazaki, K.; Yoshida, T.; Okuda, T. J.
Chem. Soc., Perkin Trans. 1 1990, 2735–2743; (f) Yoshida, T.;
Hatano, T.; Ahmed, A. F.; Okonogi, A.; Okuda, T. Tetrahedron 1991,
47, 3575–3584; (g) Santos, S. C.; Waterman, P. G. Fitoterapia 2001,
72, 95–97.
4. (a) Jin, Z.-X.; Ito, H.; Yoshida, T. Phytochemistry 1998, 48, 333–338;
(b) Yoshida, T.; Chou, T.; Shingu, T.; Okuda, T. Phytochemistry
1995, 40, 555–561; (c) Yoshida, T.; Tanei, S.; Liu, Y.-Z.; Yuan, K.; Ji,
C.-R.; Okuda, T. Phytochemistry 1993, 32, 1287–1292.
5. Several total synthesis of simple ellagitannins have been reported. (a)
Quideau, S.; Feldman, K. S. Chem. Rev. 1996, 96, 475–503; and
references cited therein; (b) Khanbabaee, K.; van Ree, T. Synthesis
2001, 1585–1610; (c) Ikeda, Y.; Nagao, K.; Tanigakiuchi, K.;
12. For
a useful review of the asymmetric reaction using chiral
oxazaborolidine, see: Cho, B. T. Tetrahedron 2006, 62, 7621–
7643.
13. The experimental method for transformation of 12 into 15: A mixture
of 12 (1 g, 1.3 mmol), Pd(OAc)2 (72 mg, 0.32 mmol), NaOAc (213 mg,
2.6 mmol), and DMA (65 ml) was heated under reflux. After 15 min,
the mixture was diluted with AcOEt and filtrated. The filtrate was
washed with water and brine, and then the organic layer was dried
over MgSO4. After evaporation of the solvent, a residue was purified
with silica gel column chromatography to afford 13 (534 mg, 64%) as
colorless needles.
BH3–THF (1.03 M, 0.96 ml) was added to a solution of 14 (266 mg,
0.96 mmol) in THF (10 ml) at 0 °C, and then the mixture was warmed
to rt. After 30 min, a solution of 13 (100 mg, 0.16 mmol) was added
dropwise at À40 °C and stirred for 72 h at the same temperature. The
mixture was poured into water and extracted with AcOEt. The
organic solution was washed with brine, dried, and evaporated to give
a residue. Silica gel column chromatography affords pure 15 (85 mg,
84%, 99% ee) as amorphous substance. The ee was determined by
HPLC analysis with Daicel Chiralcel AD.
14. Ishimaru, K.; Ishimatsu, M.; Nonaka, G.; Mihashi, K.; Iwase, Y.;
Nishioka, I. Chem. Pharm. Bull. 1988, 36, 3319–3327.