An efficient asymmetric synthesis of (-)-wodeshiol

Article abstract of DOI:10.1007/s12039-011-0078-3

An efficient synthesis of (-)-wodeshiol 1 is described. The key reactions include highly stereoselective aldol condensation of piperonal with the dianion of chiral oxazolidinone, subsequent intramolecular ring cyclization of the aldol product 8 and a dias

Full text of DOI:10.1007/s12039-011-0078-3

J. Chem. Sci. Vol. 123, No. 3, May 2011, pp. 327–330. ꢀc Indian Academy of Sciences.
An efficient asymmetric synthesis of (–)-wodeshiol
a
b
c,∗
SOON HO LEE , JAE-CHUL JUNG and OEE SOOK PARK
a
Department of Chemistry, Institute for Basic Sciences, College of Natural Sciences,
Chungbuk National University, Cheongju 361–763, Chungbuk, Korea
Department of Neuroscience and Medical Research Institute, School of Medicine,
b
Ewha Woman’s University, Seoul 158–710, Korea
c
Department of Herb Industry/Herb Resources Jungwon University, 85 Munmu-ro, Goesan-eup, Goesan-gun,
Chungbuk, 367–805, Korea
e-mail: ospark@jwu.ac.kr
MS received 19 December 2010; accepted 30 March 2011
Abstract. An efficient synthesis of (–)-wodeshiol 1 is described. The key reactions include highly stereos-
elective aldol condensation of piperonal with the dianion of chiral oxazolidinone, subsequent intramolecular
ring cyclization of the aldol product 8 and a diastereocontrolled oxygenation of dilactone 7 in good yield.
Keywords. (–)-Wodeshiol; stereoselective aldol condensation; diastereocontrolled oxygenation;
intramolecular ring cyclization.
1. Introduction
showed that positions C–1 and C–5 with dihydroxyl
19
group. In preliminary communications, we reported a
method for efficient synthesis of furofuran lignans using
highly stereoselective aldol condensation of piperonal
and intramolecular ring cyclization of aldol product. As
part of our continuing interest in the asymmetric synthe-
sis of furofuran lignans for potential use as anticancer
and anti-inflammatory agents, we established a stere-
oselective aldol condensation and a diastereocontrolled
oxygenation to accomplish asymmetric synthesis of
Furofuran lignans have stimulated significant inter-
est due to their wide range of intriguing biolog-
ical activities such as antitumor, antimitomic,
1
2
3
4
5
6
antiviral, antioxidant, antihypertensive, inhibition of
7
2+
8
plateletactivating factor (PAF), and Ca channels,
cAMP phosphodiesterase inhibitory, sodium selective
diuretic properties, and microsomal monooxygenases
inhibitory effects for insects.1 Of the furofurans, these
compounds containing 4 contiguous stereogenic centers
and one or two tertiary hydroxy functions at the bridge-
9
10
1
(
–)-wodeshiol 1. In this report, we describe an efficient
asymmetric synthesis of (–)-wodeshiol 1 through 3 step
route from the key starting material dilactone.
12
head position such as (–)-wodeshiol 1, (+)-paulownin
, (+)-isogmelinol 3, (+)-isopaulownin 4, and (+)-
13
14
13
2
15
gmelinol 5, have generated considerable and contin-
ued interest due to their unique structural characteristics
and stereochemical diversity (figure 1). The only syn-
thesis published for (–)-wodeshiol 1 is that of Corey and
Han who synthesized it from the α, β-enone using a
chiral oxazaborolidine for catalytic control of absolute
configuration.
2
. Results and discussion
16
The retrosynthetic analysis for (–)-wodeshiol 1 is sum-
marized in scheme 1. We envisioned that (–)-wodeshiol
1
could be synthesized from the key intermediate 7
in 3 steps, which has been prepared, during our syn-
(
–)-Wodeshiol 1 was isolated from Cleistanthus
20
17
thesis of (+)-sesamin and (–)-sesamin. This precur-
sor was synthesized by intramolecular ring cycliza-
tion of chiral complex 8 which was derived from
piperonal and 1,4-bis-[4-(S)-benzyl-2-oxo-oxazolidin-
collinus or Kigelia pinnata by Anjaneyulu group and
Inoue group, respectively. These spectra indicated
the equatorial disposition of the two aryl groups and
18
3
-yl]butane-1,4-dione through a diastereoselective dou-
ble aldol condensation in the presence of dibutylboron
triflate. The diastereocontrolled oxygenation of inter-
∗
For correspondence
327

328
Soon Ho Lee et al.
O
O
O
O
Ar
Ar
HO
Ar
OH
H
OH
Ar
1
(-)-wodeshiol
2 (+)-paulownin
3 (+)-isogmelinol
Ar = 3,4-methylenedioxyphenyl
Ar = 3,4-methylenedioxyphenyl Ar = 3,4-dimethoxyphenyl
O
O
Ar
H
OH
Ar
4
(+)-Isopaulownin
5 (+)-gmelinol
Ar = 3,4-dimehoxyphenyl
Ar = 3,4-methylenedioxyphenyl
Figure 1. Structures of furofuran lignans with tertiary hydroxy function at the bridge-head position.
O
O
O
O
O
O
O
O
HO
OH
HO
OH
O
O
O
O
O
O
6
(
-)-Wodesshiol 1
O
O
O
O
RN
H
O HO
O
O
H
H
H
O
O
NR
OH O
8
O
O
O
7
O
NR=Chiral Auxilary
Scheme 1. Retrosynthetic analysis of (–)-wodeshiol 1.
mediate 7 would give the compound 6 which has of HPLC analysis (91% combined yield for two steps).
23
two –OH groups at α position of bridge-head carbon. The diastereocontrolled oxygenation of dilactone 7
Reduction of compound 6 with DIBAL-H, followed with MoOPH produced dihydroxy dilactone 6 in 58%
by removal of the dihydroxyl groups of the dihydroxy yield. Interestingly, dihydroxy dilactone 6 was treated
dilactol 12 would give (–)-wodeshiol 1.
with benzyl bromide in the presence of bases such as
The synthesis of (–)-wodeshiol 1 was accomplished NaH (60%), K CO , or DIPEA to generate benzyl pro-
2
3
as depicted in scheme 2. The key intermediate 7 was tected compound. Unfortunately, these reactions failed
prepared according to the reactions as those used for to give desired product, giving starting material and/or
20
the synthesis of (+)/(–)-sesamin. Aldol condensation mono-protected product. Reduction of the dihydroxy
of boron (Z)-enolate21 (generated by treatment of N- dilactone 6 with DIBAL-H yielded dihydroxy dilac-
22
acyloxazolidinone 10 with dibuthylboron triflate and tol 12 (1:1 cis/trans ratio, 65% combined yield). The
◦
DIPEA in CH Cl at −78 C) and piperonal afforded dihydroxy dilactol 12 was reduced by treatment with
2
2
the condensation product 11 as an unstable interme- Et SiH and BF ·Et O in CH Cl to give (–)-wodeshiol
3
3
2
2
2
diate, which was not isolated but instead subjected 1 in 58% yield. (–)-Wodeshiol 1 could neither be acety-
to intramolecular ring cyclization [KH PO and H O lated in the usual way with Ac O/pyridine nor oxi-
2
4
2
2
2
(28%) in MeOH] to give dilactone 7 with 95:5 diastere- dized with Jones reagent. However, acetylation of (–)-
omeric selectivity, which was determined on the basis wodeshiol 1 with Ac O/triethylamine in the presence of
2

An efficient asymmetric synthesis of (–)-wodeshiol
329
Bn
O
9
O
O
a
b
O
NH
Bn
N
O
O
N
O
O
Bn
10
R'BO
Ar
O
O
O
O
Ar
H
c
R
d
H
H
R
H
Ar
O
O
7
Ar
OBR'
1
1
O
O
HO
Ar
OH
OH
O
Ar
OH
O
e
HO
Ar
f
HO
Ar
O
O
6
12
O
Ar
1
R' = H, (-)-Wodeshiol
g
R'O
Ar
OR'
13 R' = Ac
Ar: Methylenedioxyphenyl
O
Scheme 2. Reagents and conditions: (a) n-BuLi, succinyl chlo-
◦
◦
ride/THF, 0 C, 2 h, 86%; (b) Bu2BOTf, DIPEA/CH2Cl2, –78 C, piper-
onal, 20 min; (c) KH2PO4(aq), H2O2 (28%)/MeOH, rt, 8 h, 88% (two
◦
steps); (d) LDA, MoOPH/THF, −78 C, 4 h, 58%; (e) DIBAL-H/THF,
◦
◦
−
25 C, 8 h, 65%; (f) Et3SiH, BF3·Et2O/CH2Cl2, −40 C, 5 h, 58%; (g)
Ac2O, TEA, DMAP, rt, 2 h, 65%.
4
-dimethylaminopyridine (DMAP) gave diacetate 13,24 References
which could be easily isolated and characterized.
1. Ward R S 1982 Chem. Soc. Rev. 11 75
2
. Teles H L, Hemerly J P, Paulettit P M, Pandolfi J R C,
Araujot A R, Valentini S R, Young M C M, Bolzani V
S, Silva D H S 2005 Nat. Prod. Res. 19 319
3. Conclusion
3
. De Leon E J, Olmedo D A, Solis P N, Gupta M P,
Terencio M C 2002 Planta Med. 68 1128
In conclusion, a new and efficient method have been
developed for the synthesis of (–)-wodeshiol 1 via a
five-step route using a diastereocontrolled oxygenation
in overall 10.4% yield. This synthetic method is bet-
ter than the reported one in view of simplicity, enan-
tiomeric excess and overall yield and should be use-
ful in the synthesis of furofuran lignan which has two
tertiary hydroxly groups at bride-head carbon.
4
. Hoang V D, Tan G T, Zhang H J, Tamez P A, Nguyen
M C, Soejrto D D, Fong H H S, Pezzuto J M 2002
Phytochemistry 59 325
5. MacRae W D, Towers G H N 1984 Phytochemistry 23
1207
6
7
8
9
. Brown R C, Bataille C J, Bruton G, Hinks J D, Swain N
A 2001 J. Org. Chem. 66 6791
. Iwakami S, Ebizuka Y, Sankawa U 1990 Heterocycles
30 795
. Ichikawa K, Kinoshita T, Nishibe S, Sankawa U 1986
Chem. Pharm. Bull. 34 3514
. Nikaido T, Ohmoto T, Kinoshita T, Sankawa U, Nishibe
S, Hisada S 1981 Chem. Pharm. Bull. 29 3586
Acknowledgement
This work was supported by the Korea Research Foun-
dation Grant funded by the Korean Government (KRF-
10. Plante G E, Prevost C, Chainey A, Braquet P, Sirois P
2006–531-C00035).
1987 Am. J. Physiol. 253 R375

330
Soon Ho Lee et al.
11. Bernard C B, Arnason J T, Philogene B J R, Lam J,
Waddell T 1989 Phytochemistry 28 1373
δ 149.0, 147.9, 128.3, 120.4, 108.8, 101.4, 87.3, 85.7,
76.3; HRMS calcd for C20H19O8: 387.1080 [M+H] ,
+
1
1
2. Najera C, Yus M 2003 Curr. Org. Chem. 7 867
3. Takahashi K, Nakagawa T 1966 Chem. Pharm. Bull. 14
found: 387.1091. General procedure for the preparation
of dihydroxy dilactone 6: To a stirred solution of diiso-
propylamine (0.25 mL, 1.87 mmol), n-BuLi (1.1 mL,
641
◦
14. Tsukamoto H, Hisada S, Nishibe S 1984 Chem. Pharm.
Bull. 32 2730
1.87 mmol) in THF (3 mL) at −78 C and dilactone 7
(300 mg, 0.83 mmol) was added to the reaction mix-
◦
15. Tsukamoto H, Hisada S, Nishibe S 1985 Chem. Pharm.
Bull. 33 1232
ture at −78 C and the mixture was stirred at same the
temperature for 1 h. The reaction mixture was treated
◦
1
1
6. Xiaojun H, Corey E 1999 J. Org. Lett. 11 1871
7. Anjaneyulu A S R, Ramaiah P A, Row L R, Pelter A,
Ward R S 1975 Tetrahedron Lett. 34 2961
8. Inoue K, Inoue H, Chen C C 1981 Phytochemstry 20
with MoOPH (1.08 g, 2.49 mmol) at −78 C. As soon as
the sparingly soluble reagent has resolved, the reaction
was quenched with aqueous sodium sulfite and extracted
with ether (3 × 10 mL). The organic phase was washed
with 5% HCl and brine. The combined organic phase
was dried over anhydrous MgSO4, filtered and concen-
trated under reduced pressure to give dihydroxy dilac-
tone 6, which were purified by flash column chromatog-
raphy (silica gel, 25% ethyl acetate in hexanes) to afford
1
1
2
2271
9. Jung J C, Kim J C, Moon H I, Park O S 2006 Tetrahedron
Lett. 47 6433
0. Kim J C, Kim K H, Jung J C, Park O S 2006 Tetrahe-
dron: Asymmetry 17 3
◦
20
Selected data; 7: mp. 124–126 C [α] (c 1.0, MeOH);
D
pure dihydroxy dilactone 6 (199 mg, 58%) as a clean
−1
1
−1
IR (neat, NaCl) 1772, 1498, 1247, 1038 cm ; H NMR
solution. IR (neat, NaCl) 3329, 1780, 1488, 1042 cm
;
1
(
5
300 MHz, CDCl3) δ 6.81 (s, 4H), 6.75 (s, 2H),
.99 (s, 4H), 5.82 (s, 2H), 3.54 (s, 2H); C NMR
3
H NMR (300 MHz, CDCl ) δ 6.8 (m, 6H), 6.3 (s,
H), 6.0 (s, 4H); C NMR (75 MHz, CDCl3) δ 175.3,
48.3, 147.3, 135.2, 120.9, 108.6, 101.4, 97.8, 83.7.
HRMS calcd for C20H15O10: 415.0665 [M+H] , found:
13
13
2
1
(
1
3
75 MHz, CDCl3) δ 175.3, 149.2, 149.0, 132.4,
+
19.2, 109.4, 105.9, 102.3, 82.5, 48.9; MS(ESI) (m/z)
+
83 [M+H] , 307, 154 (base peak); HRMS calcd
4
15.0652.
1. Evans D A, Bartoli J, ShiH T L 1981 J. Am. Chem. Soc.
03 2127
+
for C20H14O8: 383.0767 [M+H] , found: 383.0695.
2
◦
16
◦
(
–)-Wodeshiol 1: mp. 153–154 C (lit. 152–153 C;
1
1
2
◦
20
D
16
lit. 150–151 C); [α] = −11.2 (c 0.7, CHCl3), (lit.
22. Van Horn D E, Masamune S 1979 Tetrahedron Lett. 24
3
D
12
24
[
α]2 = −11.7 in CHCl3; lit. [α] = −34.6 in CHCl3);
2229
D
−1 1
IR (neat, NaCl) 3432, 1602, 1256, 1032 cm ; H NMR 23. Vedejs E 1974 J. Am. Chem. 4 5944
(
(
400 MHz, CDCl3) δ 6.8–6.6 (m, 6H), 6.05 (s, 4H), 5.13 24. Anjaneyulu A S R, Ramaiah P A, Row R, Venkateswarlu
s, 2H), 4.0–2.8 (m, 4H); 13C NMR (100 MHz, CDCl3)
R, Pelter A, Ward R S 1981 Tetrahedron 37 3641