Structural revision of terpenoids with a (3Z)-2-methyl-3-penten-2-ol moiety by the synthesis of (23E)- and (23Z)-cycloart-23-ene-3β,25-diols

Article abstract of DOI:10.1021/jo070478m

(Chemical Equation Presented) Synthesis of (23E)-cycloart-23-ene-3β, 25-diol (1) and its 23Z-isomer 2 was achieved by using cycloartenol as a starting material, thus revising the proposed structure of natural 2 to 1 unequivocally. These synthetic studies

Full text of DOI:10.1021/jo070478m

Structural Revision of Terpenoids with a
(3Z)-2-Methyl-3-penten-2-ol Moiety by the
Synthesis of (23E)- and
(23Z)-Cycloart-23-ene-3â,25-diols
FIGURE 1. Structures of olefins (9 and 10).
Shunya Takahashi,*,† Hiroko Satoh,‡ Yayoi Hongo,† and
Hiroyuki Koshino*,†
identified (23E)-cycloart-23-ene-3â,25-diol (1)7,8 from
Aglaria rubiginosa, and suggested that NMR data of 1 in CDCl3
were identical with those of the compound previously re-
ported as the corresponding Z-isomer 2.2 In spite of that report,
isolation and identification of 2 and its 3-acyl derivatives9 from
the plant kingdom have been disclosed since by several
groups.10,11 These confusing results suggest that reexami-
nations were necessary to confirm the stereochemistry for not
only many other (23Z)-cycloart-23-en-25-ol derivatives with
oxygenated functional groups12,13 but also other triterpenoids
with the same side chain portion such as (23Z)-3â-acetoxy-
eupha-7,23-diene-25-ol9 and (23Z)-tirucalla-7,23-diene-3â,-
25-diol.14
RIKEN (The Institute of Physical and Chemical Research),
Wako, Saitama 351-0198, Japan, and National Institute of
Informatics, 2-1-2 Hitotsubashi, Chiyoda-ku,
Tokyo 101-8430, Japan
shunyat@riken.jp; koshino@riken.jp
ReceiVed March 12, 2007
To distinguish the stereochemistry of a 1,2-disubstituted
double bond, the vicinal coupling constant value is generally
used, but in the case of the above-mentioned compounds,
olefinic proton signals are overlapped in CDCl3 solution. A 13
C
NMR chemical shift comparison is also a very useful and
promising method for the determination of the double bond
stereochemistry. In previous papers, some of us (H.K. and H.S.)
developed a new stereochemical coding method, CAST (CA-
nonical-representation of STereochemistry)15-17 and successfully
applied it to a database-oriented 13C NMR chemical shift
prediction system, called CAST/CNMR.18-20 In the course of
studies applying CAST/CNMR to cycloart-23-en-25-ol deriva-
tives, we could not find reliable 13C NMR data of compounds
with the 2-methyl-3-penten-2-ol moiety that possesses Z
Synthesis of (23E)-cycloart-23-ene-3â,25-diol (1) and its
23Z-isomer 2 was achieved by using cycloartenol as a starting
material, thus revising the proposed structure of natural 2 to
1 unequivocally. These synthetic studies revealed that the
structural revision (Z-form f E-form) should also be applied
to terpenoids such as (23Z)-3â-acetoxyeupha-7,23-diene-25-
ol, (23Z)-tirucalla-7,23-diene-3â,25-diol, quadrangularol A,
quadrangularic acid K, and daurichromene C.
(7) Teresa et al. reported isolation of its 3â-acetyl derivative from
Euphorbia broteri, and the 13C NMR data. Determination of the stereo-
chemistry, however, was not denoted, see: Teresa, J. D.; Urones, J. G.;
Marcos, I. S.; Basabe, P.; Cuadrado, M. J. S.; Moro, R. F. Phytochemistry
1987, 26, 1767-1776.
Cycloart-23-ene-3â,25-diol was first discovered from
Spanish moss (Tillandsia usneoides) by Djerassi and
McCrindle in 1962.1 Greca et al.2 isolated the diol from Juncus
effusus, and determined its structure to be (23Z)-cycloart-
23-ene-3â,25-diol (2);3-5 the double bond stereochemistry
was assigned by the small vicinal coupling constant values,
which were extracted from overlapping olefinic signals
with a half-bandwidth of 8 Hz. On the contrary Weber et al.6
(8) Cabrera, G. M.; Gallo, M.; Seldes, A. M. J. Nat. Prod. 1996, 59,
343-347.
(9) Kitajima, J.; Kimizuka, K.; Tanaka, Y. Chem. Pharm. Bull. 1998,
46, 1408-1411.
(10) Harding, W. W.; Jacobs, H.; Lewis, P. A.; McLean, S.; Reynolds,
W. F. Nat. Prod. Lett. 2001, 15, 253-260.
(11) Luo, H.-F.; Li, Q.; Yu, S.; Badger, T. M.; Fang, N. J. Nat. Prod.
2005, 68, 94-97.
(12) Banskota, A. H.; Tezuka, Y.; Tran. K. Q.; Tanaka, K.; Saiki, I.;
Kadota, S. J. Nat. Prod. 2000, 63, 57-64.
* Address correspondence to this author. Phone: +81-48-467-9223. Fax:
+81-48-462-4627.
(13) Banskota, A. H.; Tezuka, Y.; Tran. K. Q.; Tanaka, K.; Saiki, I.;
Kadota, S. Chem. Pharm. Bull. 2000, 48, 496-504.
(14) Luo, X.-D.; Wu, S.-H.; Ma, Y.-B.; Wu, D.-G. Phytochemistry 2000,
54, 801-805.
† RIKEN.
‡ National Institute of Informatics.
(1) Djerassi, C.; McCrindle, R. J. Chem. Soc. C 1962, 4034-4039.
(2) Greca, M. D.; Fiorentino, A.; Monaco, P.; Previtera, L. Phytochem-
istry 1994, 35, 1017-1022.
(3) Tanaka, R.; Ida, T.; Kita, S.; Kamisako, W.; Matsunaga, S. Phy-
tochemistry 1996, 41, 1163-1168.
(4) Akihisa, T.; Kimura, Y.; Kasahara, Y.; Kumaki, K.; Thakur, S.;
Tamura, T. Phytochemistry 1997, 46, 1261-1266.
(5) Sutthivaiyakit, S.; Thapsut, M.; Prachayasittikul, V. Phytochemistry
2000, 53, 947-950.
(6) The stereochemistry was determined by the vicinal coupling constant
value (3J23H,24H ) 16 Hz) that was recorded in benzene-d6 solution, see:
Weber, S.; Puripattanavong, J.; Brecht, V.; Frahm, A. W. J. Nat. Prod.
2000, 63, 636-642.
(15) Satoh, H.; Koshino, H.; Funatsu, K.; Nakata, T. J. Chem. Inf.
Comput. Sci. 2000, 40, 622-630.
(16) Satoh, H.; Koshino, H.; Funatsu, K.; Nakata, T. J. Chem. Inf.
Comput. Sci. 2001, 41, 1106-1112.
(17) Satoh, H.; Koshino, H.; Nakata, T. J. Comput. Aided Chem. 2002,
3, 48-55.
(18) Satoh, H.; Koshino, H.; Uzawa, J.; Nakata, T. Tetrahedron 2003,
59, 4539-4547.
(19) Satoh, H.; Koshino, H.; Uno, T.; Koichi, S.; Iwata, S.; Nakata, T.
Tetrahedron 2005, 61, 7431-7437.
(20) Koshino, H.; Satoh, H.; Yamada, T.; Esumi, Y. Tetrahedron Lett.
2006, 47, 4623-4626.
10.1021/jo070478m CCC: $37.00 © 2007 American Chemical Society
Published on Web 05/17/2007
4578
J. Org. Chem. 2007, 72, 4578-4581

SCHEME 1. Synthesis of (23E)-Cycloart-23-ene-3â,25-diol (1) and Its 23Z-Isomer (2)
TABLE 1. 1H NMR Data (δ) for (23E)-Cycloart-23-ene-3â,25-diol (1) and Its (23Z)-Isomer 2
position
1
2
2a
2b
2c
H-22a
H-22b
H-23
H-24
H-26
H-27
1.74 m
2.17 ddd (14.0, 3.3, 3.3)
5.60 m
5.60 m
1.31 s
1.32 s
2.13 dddd (14.8, 9.9, 8.8, 1.7)
2.38 dddd (14.8, 6.1, 3.8, 1.7)
5.31 ddd (12.1, 8.8, 6.1)
5.53 ddd (12.1, 1.7, 1.7)
1.36 s
5.59 md
5.59 md
1.33 s
5.60 dd (4.1, 3.1)
5.60 dd (4.1, 3.1)
1.32 s
5.59 m
5.59 br d (8.0)
1.32 s
1.37 s
1.33 s
1.32 s
1.32 s
a Reference 2. b Reference 3. c Reference 9. d Half-bandwidth of 8 Hz.
stereochemistry.21-25 Total synthesis of 1 and 2 also has not
been reported. Therefore, we planned to prepare authentic
samples to add into the database of CAST/CNMR. Described
herein are the stereoselective synthesis of (23E)-cycloart-23-
ene-25-ol (1) and its Z-isomer 2, and a detailed comparison of
their NMR data with those from the literature.2,3,9,11-14
Prior to the synthesis of 1 and 2, simple model compounds,
(3E)- and (3Z)-2-methyl-3-decen-2-ol (9 and 10),22 were
prepared (Figure 1).26 The 1H NMR spectrum of 9 revealed the
olefinic protons H-3 and H-4 at δ 5.60-5.61 as complicated
multiplets whereas those of 10 were observed at δ 5.48 (dt, J3,4
) 11.6 Hz, J3,5 ) 1.8 Hz) and δ 5.31 (dt, J3,4 ) 11.6 Hz, J4,5
) 7.1 Hz). In the 13C NMR spectra, compounds 9 and 10 each
showed two olefinic carbons C-3 and C-4 at 137.8 and 127.4
ppm, and 136.7 and 131.4 ppm, respectively. It should be
mentioned that the misassignment with regard to E/Z stereo-
chemistry was made in ref 22. In the case of a compound
showing overlapping olefinic signals in the 1H NMR spectrum
such as 9, 1H NMR measurement in a solvent other than CDCl3
should be examined to determine the geometry of the double
bond clearly (vide infra). Compared with the reported data,2,3,5
it seemed that the relationship between H-23 and H-24 of all
reported natural cycloart-23-ene-3â,25-diol should be E. To
confirm this precisely, we synthesized both isomers of cycloart-
23-ene-3â,25-diol as follows. Cycloartenol (3), prepared from
γ-oryzanol,27-29 was epoxidized with mCPBA to give a mixture
of epoxides 4 in 87% yield (Scheme 1). Nucleophilic opening
of 4 with a selenide anion prepared from diphenyldiselenide-
sodium borohydride in ethanol30,31 afforded a mixture of selenide
alcohols 5 in 92% yield. Oxidation of the compound with
hydrogen peroxide in the presence of pyridine gave the E-olefin
1
1 exclusively in 90% yield. In the H NMR spectrum of 1 in
CDCl3, two olefinic protons were observed at δ 5.60 as a
multiplet (Table 1), but the large coupling constant value of J
) 15.5 Hz for the E double bond was observed from 13C satellite
signals by 13C selectively decoupled 1H NMR experiments
1
irradiating the C-23 or C-24 resonance.32 Additionally, the H
NMR spectrum of 1 in C6D6 supported the E geometry based
on a large vicinal coupling constant value (J ) 15.8 Hz) between
H-23 and H-24 whose signals were observed at δ 5.68 (ddd, J
) 15.8, 8.3, 6.7 Hz) and 5.68 (d, J ) 15.8 Hz), respectively.6
In the 13C NMR spectra (CDCl3), two olefin carbons and
quaternary C-25 were observed at 125.6, 139.4, and 70.7 ppm,
respectively (Table 2). The 1H and 13C NMR spectral data of 1
(21) Fattorusso, E.; Mango, S.; Santacroce, C.; Sica, D.; Impellizzeri,
G.; Mangiafico, S.; Oriente, G.; Piattelli, M.; Sciuto, S. Phytochemistry
1975, 14, 1579-1582.
(22) Dittmer, D. C.; Zhang, Y.; Discordia, R. P. J. Org. Chem. 1994,
59, 1004-1010.
(23) Guijarro, A.; Yus, M. Tetrahedron 1994, 50, 13269-13276.
(24) He, Z.-D.; Lau, K.-M.; But, P. P.-H.; Jiang, R.-W.; Dong, H.; Ma,
S.-C.; Fung, K.-P.; Ye, W.-C.; Sun, H.-D. J. Nat. Prod. 2003, 66, 851-
854.
(25) Iwata, N.; Wang, N.; Yao, X.; Kitanaka, S. J. Nat. Prod. 2004, 67,
1106-1109.
(27) Tsuchiya, T.; Kato, A.; Endou, T. Tokyo Kogyo Shikensho Houkoku
1956, 51, 359.
(28) Ohta, G.; Shimizu, M. Chem. Pharm. Bull. 1958, 6, 325-326.
(29) Yoshida, K.; Hirose, Y.; Imai, Y.; Kondo, T. Agric. Biol. Chem.
1989, 53, 1901-1912.
(30) Sharpless, K. B.; Lauer, R. F. J. Am. Chem. Soc. 1973, 95, 2697-
2699.
(31) Miyashita, M.; Hoshino, M.; Yoshikoshi, A. Tetrahedron Lett. 1988,
29, 347-350.
(32) Muller, N. J. Chem. Phys. 1962, 37, 2729-2730.
(26) These compounds were prepared from n-heptanal in 2 steps: (i)
(EtO)2P(dO)CH2CO2Et, NaH, THF, 0 °C, 90% (E/Z ) 97/3) or (o-TolO)2P-
(dO)CH2CO2Et, Triton B, THF, -78 to 0 °C, 82% (E/Z ) 20/80); (ii)
MeLi, THF, -78 °C, 88-94%.
J. Org. Chem, Vol. 72, No. 12, 2007 4579

TABLE 2. 13C NMR Data (δ) for Synthetic and Natural Compounds 1, 2, and 11-15
CDCl3
pyridine-d5
positiona
1
2
2b
2c
11c
12d
15e
1
2
13f
14g
C-22 (5′)
C-23 (6′)
C-24 (7′)
C-25 (8′)
C-26 (9′)
C-27 (10′)
39.0
125.6
139.4
70.7
30.0
29.9
34.6
130.2
137.4
71.6
31.3
31.1
39.0
139.3h
125.6h
70.8
29.9
29.9
39.0
125.6
139.3
70.8
29.9
29.9
38.0
126.0
139.1
70.7
29.9
29.9
38.9
125.6
139.4
70.7
29.9
29.9
42.3
125.3
139.2
70.8
29.9
29.9
39.5
124.5
141.7
69.7
30.9
30.9
35.0
129.1
139.5
70.7
31.9
31.8
39.5
124.6
141.6
69.7
30.5
30.5
39.3
124.4
141.3
69.6
30.0
30.6
a In the case of compound 15, the numbering system in parentheses is used. b Reference 2. c Reference 9. d Reference 14. e Reference 25. f Reference 13.
g Reference 12. h These assignments should be interchanged.
FIGURE 2. Originally proposed structures of terpenoids (11-15).
FIGURE 3. Revised structures of terpenoids (11-15).
in CDCl3 were consistent with those of the reported Z-isomer.3,4,6
Synthesis of the corresponding Z-isomer (2) started from 1. The
double bond in the latter was oxidized under Lemieux-Johnson
oxidation to afford aldehyde 6 in 66% yield. The Wittig reaction
of 6 with Ando’s protocol33 gave a desired Z-ester 8 in 70%
yield along with the corresponding E-isomer 7 (15%). After
separation by chromatography on silica gel, the Z-ester 8 was
treated with a small excess of methyllithium in ether at -78
°C, giving tert-alcohol 2 in 88% yield. The spectrum of 2 in
CDCl3 showed the olefinic protons H-23 at δ 5.31 (ddd, J)
12.1, 8.8, 6.1 Hz) and H-24 at δ 5.53 (ddd, J ) 12.1, 1.7, 1.7
Hz), which were clearly different from the reported data for
2.2,3,5 On the basis of these results, we concluded that the
structure of the previously reported Z-isomer 2 and its 3-acyl
derivatives2-5,9-11 should be revised to that of the corresponding
E-isomers.
as shown in Table 2. Therefore, the geometry of the terminal
olefin should be revised to the E stereochemistry as shown in
Figure 3.
In summary, we synthesized both geometrical isomers of
cycloart-23-ene-3â,25-diol (1 and 2). The detailed NMR studies
1
including complete H and 13C NMR assignments in CDCl3,
pyridine-d5, C6D6, and methanol-d4 (see the Supporting Infor-
mation) of 1 and 2 together with model compounds 9 and 10,
which were confirmed by analyses of 2D DQFCOSY, HSQC,
and HMBC spectra, revealed that most terpenoids with a (3Z)-
2-methyl-3-penten-2-ol moiety such as (23Z)-cycloart-23-ene-
3â,25-diol (2), (23Z)-3â-acetoxyeupha-7,23-diene-25-ol (11),
(23Z)-tirucalla-7,23-diene-3â,25-diol (12), quadrangularol A
(13), quadrangularic acid K (14), and daurichromene C (15),
should be revised to the corresponding E-isomers (1, and 16-
20), respectively. Further work on these studies is in progress.
The (3Z)-2-methyl-3-penten-2-ol moiety is recognized as a
common substructure included in many natural products such
as (23Z)-3â-acetoxyeupha-7,23-diene-25-ol (11),9 (23Z)-tiru-
calla-7,23-diene-3â,25-diol (12),11 quadrangularol A (13),13
quadrangularic acid K (14),12 and daurichromene C (15)25
(Figure 2). However, spectral data of the olefin part in such
natural products were well matched with those of synthetic 1
Experimental Section
Epoxides (4). To a stirred solution of 3 (1.05 g, 2.5 mmol) in
dichloromethane (20 mL) was added m-chloroperoxybenzoic acid
(70-75% assay, 0.73 g, ca. 3.0 mmol) at 0 °C. The mixture was
stirred at 0 °C to rt for 5 h, and then poured into aqueous saturated
NaHCO3/Na2S2O3 (1:1) with stirring. The resulting mixture was
extracted with dichloromethane. The extracts were washed with
water and brine, dried, and concentrated. Chromatography on silica
gel with n-hexane-ethyl acetate (10:1) as the eluent yielded 4 (0.95
(33) Ando, K. J. Org. Chem. 1997, 62, 1934-1939.
4580 J. Org. Chem., Vol. 72, No. 12, 2007

g, 87%) as an amorphous solid. IR (neat) 3320, 3039, 2927, 2860,
1445, 1378, 1099, 1046 cm-1; 1H NMR (400 MHz, CDCl3) δ 3.27
(1H, m), 2.68 (1H, t, J ) 6.3 Hz), 2.02-0.73 (25H, m), 1.30 (3H,
br s), 1.26 (3H, br s), 0.96 (6H, s), 0.89 (3H, s), 0.88 (3H, d, J )
6.1 Hz), 0.80 (3H, s), 0.55 (1H, br d, J ) 3.9 Hz), 0.32 (1H, br d,
J ) 3.9 Hz); 13C NMR (100 MHz, CDCl3) δ 78.8, 64.9, 64.8, 58.4,
58.1, 52.2, 52.1, 48.8, 47.9, 47.1, 45.2, 40.4, 35.9, 35.8, 35.5, 32.9,
32.8, 32.7, 32.6, 31.9, 30.3, 29.9, 29.7, 28.1, 28.0, 26.4, 26.0, 25.9,
25.6, 25.4, 24.9, 21.1, 19.9, 19.3, 18.7, 18.6, 18.2, 18.1, 18.0, 14.0;
HRMS (EI) calcd for C30H50O2 (M+) 442.3811, found 442.3811.
Selenoalcohols (5). At 0 °C, acetic acid (25 µL, 0.44 mmol)
was added to an ethanolic solution of Na+[PhSeB(OEt)3]-, prepared
by the reduction of diphenyl diselenide (423 mg, 1.36 mmol) with
sodium borohydride (103 mg, 2.72 mmol) in ethanol (8 mL), and
the mixture was stirred at the same temperature for 10 min. To the
solution was added dropwise a solution of 4 (400 mg, 0.90 mmol)
in ethanol (3 mL). The resulting mixture was stirred at 80 °C for
5 h, cooled, diluted with ether, and then washed with water and
brine, dried, and concentrated. Chromatography on silica gel with
n-hexane-ethyl acetate (1:0 f 10:1 f 4:1) as the eluent yielded
5 (501 mg, 92%) as an amorphous solid. IR (neat) 3304, 3052,
(100 MHz, CDCl3) δ 203.5, 78.7, 52.2, 51.1, 48.9, 47.9, 47.0, 45.4,
40.4, 35.4, 32.7, 31.9, 30.3, 29.8, 28.3, 26.3, 26.1, 25.9, 25.4, 21.0,
19.8, 19.6, 19.3, 18.0, 14.0; HRMS (EI) calcd for C26H42O2 (M+)
386.3185, found 386.3179.
Râ-Unsaturated esters (7 and 8). To a stirred suspension of
NaH (60% oil dispersion, 14.5 mg, 0.36 mmol) in THF (1.0 mL)
was added dropwise ethyl di-O-tolylphosphonoacetate (106 µL, 0.36
mmol) at 0 °C, and the mixture was stirred at 0 °C for 30 min. To
this solution was added a solution of 6 (31 mg, 0.08 mmol) in THF
(0.2 mL) at -78 °C and the mixture was stirred at -78 °C for 1 h
and then -78 to 0 °C for 1 h. After addition of water, the mixture
was extracted with ether. The extracts were washed successively
with water and brine, dried, and concentrated. The residue was
purified by preparative TLC (n-hexane-ethyl acetate (4:1), 8
developments) to give 7 (5.8 mg, 16%) and 8 (25.6 mg, 70%).
7: [R]25 +39.1 (c 0.12, CHCl3); IR (neat) 3426, 3031, 2931,
D
2864, 1702, 1648, 1442, 1366, 1305, 1267, 1162, 1044, 1023, 981
cm-1; 1H NMR (400 MHz, CDCl3) δ 6.95 (1H, ddd, J ) 15.7, 8.8,
6.3 Hz), 5.80 (1H, d, J ) 15.7 Hz), 4.18 (2H, q, J ) 7.3 Hz), 3.26
(1H, m), 2.32 (1H, dd, J ) 14.1, 6.3 Hz), 2.02-0.75 (22H, m),
1.28 (3H, t, J ) 7.3 Hz), 0.97 (3H, s), 0.96 (3H, s), 0.89 (3H, d, J
) 6.3 Hz), 0.88 (3H, s), 0.80 (3H, s), 0.55 (1H, d, J ) 3.9 Hz),
0.32 (1H, d, J ) 3.9 Hz); 13C NMR (100 MHz, CDCl3) δ 166.6,
148.4, 122.4, 78.8, 60.1, 52.0, 48.8, 48.0, 47.1, 45.4, 40.5, 39.3,
36.0, 35.5, 32.7, 31.9, 30.4, 29.9, 28.1, 26.4, 26.1, 26.0, 25.4, 21.1,
19.9, 19.3, 18.6, 18.0, 14.3, 14.0; HRMS (EI) calcd for C30H48O3
(M+) 456.3603, found 456.3621.
1
2932, 2864, 1578, 1470, 1437, 1377, 1047, 1022 cm-1; H NMR
(400 MHz, CDCl3) δ 7.61-7.55 (2H, m), 7.26-7.22 (3H, m), 3.28
(1H, m), 3.09 (0.6H, dd, J ) 8.7, 2.0 Hz), 3.01 (0.4H, dd, J )
11.7, 2.0 Hz), 2.02-0.71 (47H, m), 0.55 (0.4H, d, J ) 3.9 Hz),
0.54 (0.6H, d, J ) 3.9 Hz), 0.33 (0.4H, d, J ) 3.9 Hz), 0.32 (0.6H,
d, J ) 3.9 Hz); 13C NMR (100 MHz, CDCl3) δ 133.7, 133.4, 131.4,
129.1, 127.2, 127.1, 78.8, 72.9, 72.8, 66.8, 65.7, 52.3, 52.2, 48.7,
48.0, 47.1, 40.5, 36.4, 35.9, 35.5, 35.4, 35.2, 35.1, 32.9, 31.9, 30.4,
29.9, 29.5, 28.1, 27.9, 26.9, 26.8, 26.4, 26.2, 25.4, 21.1, 19.9, 18.6,
18.0, 17.9, 13.9; HRMS (EI) calcd for C36H56O2Se (M+) 600.3445,
found 600.3420.
(23E)-Cycloart-23-ene-3â,25-ol (1). Aqueous hydrogen peroxide
(15%, 2 mL, ca. 8.9 mmol) was added to a solution of 5 (333 mg,
0.56 mmol) and pyridine (0.16 mL) in dichloromethane (4 mL) at
0 °C. The mixture was stirred at 0 °C to rt for 13 h, and then diluted
with ether. The solution was washed with 10% aqueous copper
sulfate, water, and brine, and then dried and concentrated. Chro-
matography on silica gel with n-hexane-ethyl acetate (1:0 f 10:1
f 4:1) as the eluent gave 1 (221 mg, 90%) as a crystalline solid.
Mp 199-200 °C (ethyl acetate); [R]25D +36.2 (c 0.13, CHCl3); IR
(neat) 3281, 3049, 2928, 2865, 1457, 1441, 1375, 1143, 1049, 970
cm-1; HRMS (EI) calcd for C30H50O2 (M+) 442.3811, found
442.3812.
8: [R]24 +22.6 (c 0.31, CHCl3); IR (neat) 3300, 3030, 2925,
D
1
2860, 1718, 1638, 1445, 1373, 1170, 1037, 1020 cm-1; H NMR
(400 MHz, CDCl3) δ 6.25 (1H, ddd, J ) 11.2, 8.3, 6.8 Hz), 5.80
(1H, dt, J ) 11.2, 1.9 Hz), 4.16 (2H, q, J ) 7.4 Hz), 3.28 (1H, m),
2.64-2.58 (2H, m), 2.03-0.75 (21H, m), 1.28 (3H, t, J ) 7.4 Hz),
0.98 (3H, s), 0.96 (3H, s), 0.90 (3H, d, J ) 6.6 Hz), 0.89 (3H, s),
0.81 (3H, s), 0.55 (1H, J ) 3.9 Hz), 0.33 (1H, d, J ) 3.9 Hz); 13
C
NMR (100 MHz, CDCl3) δ 166.6, 149.8, 120.4, 78.8, 59.7, 52.4,
48.8, 48.0, 47.1, 45.4, 40.5, 36.7, 35.7, 35.6, 32.8, 32.0, 30.4, 29.9,
28.1, 26.4, 26.1, 26.0, 25.5, 21.1, 20.0, 19.3, 18.5, 18.1, 14.3, 14.0;
HRMS (EI) calcd for C30H48O3 (M+) 456.3603, found 456.3587.
(23Z)-Cycloart-23-ene-3â,25-ol (2). To a stirred solution of 8
(17.0 mg, 0.04 mmol) in ether (0.6 mL) was added a 0.98 M ether
solution of methyllithium (0.4 mL, 0.39 mmol) at -78 °C, and the
mixture was stirred at -78 °C for 2 h, and then 0 °C for 30 min.
After being quenched with saturated aqueous NH4Cl, the mixture
was extracted with ether. The extracts were washed successively
with water and brine, dried, and concentrated. Chromatography on
silica gel with n-hexane-ethyl acetate (10:0 f 4:1) as the eluent
gave 2 (15.5 mg, 94%) as a white solid. Mp 145-147 °C
Aldehyde (6). To a stirred solution of 1 (136 mg, 0.31 mmol)
in tetrahydrofuran (3 mL) and water (1 mL) was added dropwise
a solution of OsO4 (ca. 0.008 mmol) in 2-methyl-2-propanol (0.1
mL) at rt. After the solution was stirred for few minutes, NaIO4
(263 mg, 1.23 mmol) was added in portions. After being stirred
for an additional 12 h, the mixture was filtered through a pad of
Celite, and the filtrate was extracted with ethyl acetate. The extracts
were washed successively with aqueous Na2S2O3, water, saturated
aqueous NaHCO3, water, and brine, dried, and concentrated.
Chromatography on silica gel with n-hexane-ethyl acetate (1:0 f
10:1 f 4:1) as the eluent yielded 6 (78 mg, 66%) as an amorphous
(n-hexane-ether); [R]24 +31.2 (c 0.16, CHCl3); IR (neat) 3336,
D
3047, 3010, 2948, 2933, 2861, 1636, 1449, 1373, 1359, 1335, 1146,
1053, 1025, 951 cm-1; HRMS (EI) calcd for C30H50O2 (M+)
442.3811, found 442.3811.
Acknowledgment. This work was supported by the Special
Project Funding for Basic Science (Chemical Biology Project)
from RIKEN and the Funding for Joint Research from the
National Institute of Informatics.
solid. [R]24 +25.6 (c 0.31, CHCl3); IR (neat) 3440, 3040, 2930,
D
1
2702, 1716, 1447, 1438, 1374, 1362, 1335, 1022 cm-1; H NMR
(400 MHz, CDCl3) δ 9.75 (1H, dd, J ) 3.4, 1.5 Hz), 3.27 (1H,
ddd, J ) 11.2, 4.4, 3.9 Hz), 2.46 (1H, dd, J ) 15.6, 1.9 Hz), 2.16
(1H, ddd, J ) 15.6, 9.3, 3.4 Hz), 2.09-0.72 (21H, m), 1.01 (3H,
s), 0.96 (3H, d, J ) 6.3 Hz), 0.95 (3H, s), 0.89 (3H, s), 0.80 (3H,
s), 0.55 (1H, d, J ) 3.9 Hz), 0.33 (1H, d, J ) 0.39 Hz); 13C NMR
Supporting Information Available: 1H and 13C NMR data of
1, 2, 9, and 10, and NMR spectra of 1, 2, and 4-8. This material
is available free of charge via the Internet at http://pubs.acs.org.
JO070478M
J. Org. Chem, Vol. 72, No. 12, 2007 4581