Synthesis of α-tocopherol analogs with unsaturated side chain and their transformation into the corresponding chromans with ω-functionalized side chain

Article abstract of DOI:10.1023/A:1015086326009

α-Tocopherol analogs with double bond-containing side chains were synthesized by condensation of trimethylhydroquinone with optically active (3R/S,4S)-3,4,8-trimethylnona1,7-dien-3-ol and linalool in the presence of the zeolite-containing Tseokar-10 aluminosilicate. Ozonolysis of these compounds gave the corresponding chromans with ω-formyl or (after hydride reduction) ω-hydroxyl groups in the side chain.

Full text of DOI:10.1023/A:1015086326009

Russian Chemical Bulletin, International Edition, Vol. 50, No. 11, pp. 2227—2230, November, 2001
2227
Synthesis of α-tocopherol analogs with unsaturated side chain
and their transformation into the corresponding chromans with
ω-functionalized side chain
V. N. Odinokov*, A. Yu. Spivak, G. A. Emelianova, B. I. Kutepov, and L. M. Khalilov
Institute of Petrochemistry and Catalysis, Bashkortostan Republic Academy of Sciences
and Ufa Scientific Center of the Russian Academy of Sciences,
141 prosp. Oktyabrya, 450075 Ufa, Russian Federation.
Fax: +7 (347 2) 31 2750. E-mail: ink@anrb.ru
α-Tocopherol analogs with double bond-containing side chains were synthesized by
condensation of trimethylhydroquinone with optically active (3R/S,4S)-3,4,8-trimethylnona-
1,7-dien-3-ol and linalool in the presence of the zeolite-containing Tseokar-10 aluminosili-
cate. Ozonolysis of these compounds gave the corresponding chromans with ω-formyl or
(after hydride reduction) ω-hydroxyl groups in the side chain.
Key words: α-tocopherol analogs, trimethylhydroquinone, isoprenoid vinylcarbinols,
condensation, catalysis, aluminosilicates, ozonolysis, hydride reduction.
In view of the intensive search for biologically active
analogs of vitamin E with a modified side chain,1 we
investigated the possibility of synthesizing its analogs
with shortened functionalized side chains.2 These com-
pounds present interest as objects of biological studies
and as building blocks for the synthesis of other vitamin
E analogs.
The first step used in this work was acid-catalyzed
coupling of trimethylhydroquinone (TMHQ) with al-
lylic isoprenoid alcohols.3 The usual catalysts are un-
suitable for reactions of tertiary vinylcarbinols with un-
saturated isoprenoid groups because in this case, the
reaction is complicated by side cyclization resulting in
tricyclic esters.4,5
GLC data, ee ∼50%, as in the initial 1, see Ref. 2). The
diastereomer mixture 3 was transformed into a mixture
of the corresponding acetates 4 and characterized.
Under the same conditions, the condensation of
TMHQ with 2 is less selective, resulting in the forma-
tion of a considerable amount of tricyclic isomer 6
besides the target chromanol 5. Compounds 5 and 6
were separated and characterized as the corresponding
acetates 7 and 8. The best yield of the target chromanol
5 is obtained by performing the reaction in heptane (the
5 : 6 ratio is 2 : 1),* while the reaction in aromatic
solvents (benzene, toluene) gives a nearly equimolar
mixture of compounds 5 and 6, and the reaction in
dioxane does not proceed at all.
We have reported previously the use of the Tseokar-
10 aluminosilicate for the synthesis of optically active
analogs of α-tocopherol with a saturated isoprenoid side
chain.2 The AShNTs-3 and Tseokar-2 aluminosilicates
have been used for TMHQ condensation with isophytol
and dihydrolinalool.6 In this work, we have studied the
capacity of the aluminosilicate catalyst Tseokar-10 in
the synthesis of chromanols with an isoprenoid side
chain containing a terminal isopropylidene group.
(3R/S,4S)-3,4,8-Trimethylnona-1,7-dien-3-ol (1) (a 1 : 1
mixture of (3R,4S)-erythro- and (3S,4S)-threo-diastere-
omers, ee ∼50%) and linalool (2) served as the allyl
isoprenoid alcohols for the condensation with TMHQ.
It was found that the reaction of TMHQ with 1 in
boiling heptane* in the presence of the Tseokar-10
aluminosilicate gives a mixture of diastereomeric optically
active chromanols 3 in 54% yield (erythro/threo ∼1 : 1,
The difference between the selectivities observed in
the reactions of TMHQ with 1 and 2 may be due to easy
cyclization of intermediate 9 (see Refs. 7 and 8), whereas
in the reaction of TMHQ with 1, the cyclization of the
similar intermediate to compound 10 containing a seven-
membered ring is hampered.
The ozonolysis of olefins
4
and
7
in
a
CH2Cl2—MeOH mixture with subsequent reduction of
the peroxide products by Me2S 9 yields the correspond-
ing aldehydes and their acetals in a total yield of no
more than 35%. The oxidative cleavage of chromanols 4
and 7 was carried out using the procedure of ozonoly-
sis10 in aqueous acetone in the presence of Ba(OH)2,
which gave aldehydes 11 and 12 in 52 and 80% yields,
respectively, in one step. The hydride reduction of 11
and 12 yielded the corresponding alcohols 13 and 14.
Compounds 11—14 can serve as synthons for various
α-tocopherol analogs.
The 13C NMR spectra of aldehydes 11 and alcohols
13, like those of compounds 3 and 4, exhibit double sets
of signals (Table 1) for atoms that experience the influ-
* Under more drastic conditions (in boiling nonane), the
selectivity of the reaction is much lower and a complex
mixture of products is obtained.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2127—2130, November, 2001.
1066-5285/01/5011-2227 $25.00 © 2001 Plenum Publishing Corporation

2228
Russ.Chem.Bull., Int.Ed., Vol. 50, No. 11, November, 2001
Odinokov et al.
Scheme 1
RO
RO
a
O
O
OH
1
6, 8
3, 4
6: R = H
3: R = H
b
4: R = Ac
b
8: R = Ac
HO
a
RO
OH
OH
O
2
9
5, 7
4
7
5: R = H
b
7: R = Ac
c
c
AcO
AcO
O
O
O
O
HO
11
12
d
d
O
AcO
AcO
10
OH
OH
O
O
13
14
Reagents and conditions: a. TMHQ/Tseokar 10, n-C7H16; b. Ac2O/Py; c. O3/Me2CO/Ba(OH)2; d. NaBH4/MeOH.
column with the Chromaton N-AW-DMCS and SE-30 (5%)
ence by the chiral 2- and 1´-centers, which is typical of
diastereomer mixtures.2,11 The presence of two doublets
of equal intensities corresponding to the protons of the
methyl group bound to C(1´) in the region of δ 0.92—1.02
in the 1H NMR spectra of compounds 3, 4, 11, and 13
implies that these products are equimolar mixtures of
(2R,1´S)-erythro- and (2S,1´S)-threo-diastereomers.
–1
stationary phase at a temperature of 50—300 °C (8 K min
)
using helium as the carrier gas). The preparative resolution of
acetates 7 and 8 was carried out using a Carlo Erba chromato-
graph (a 6000½6 mm column) with the SE-30 stationary
phase, a thermostat temperature of 300 °C, and helium as
the carrier gas. Optical rotation was measured using
a
Perkin—Elmer-141 polarimeter.
6-Hydroxy-2,5,7,8-tetramethyl-2-[2S-(6-methylhept-5-en-
2-yl)]chromans (3). A mixture (prepared by a known proce-
dure2) of alcohols 1 (2.5 g, 13.74 mmol) was added dropwise
(Ar, 98 °C) to a suspension of TMHQ (1.04 g, 6.87 mmol) and
the powdered Tseokar-10 catalyst (2.4 g) (a zeolite-containing
aluminosilicate catalyst for the cracking of petroleum fractions,
manufactured at the Salavatnefteorgsintez plant) in 30 ml of
dry n-heptane. The reaction mixture was refluxed for 5 h,
cooled to ∼20 °C, and filtered. The filtrate was concentrated
and the residue was chromatographed on SiO2. Elution first
with n-hexane and then with an n-hexane—Et2O mixture
Experimental
IR spectra were recorded on a Specord 75-IR spectrometer
(in thin film). UV spectra were measured using a Specord
Ì-40 instrument. 1H and 13C NMR spectra were run on a
Bruker AM-300 spectrometer (300.13 and 75 MHz for 1H and
13C, respectively) in CDCl3. The chemical shifts are given in
the δ scale relative to Me4Si (internal standard). GLC analysis
was performed using a Chrom-5 chromatograph (a 2400½4 mm

α-Tocopherol analogs: synthesis, ozonolysis
Russ.Chem.Bull., Int.Ed., Vol. 50, No. 11, November, 2001 2229
Table 1. 13C NMR spectral data (δ) for compounds 3, 4, 7, 8, 11—14
C atom,
group
3
4
7
8
11
12
13
14
C(2)
C(3)
C(4)
75.57
77.20
77.57
28.63
29.12
20.27
74.71
30.99
20.45
75.92
47.99
33.37
76.84
77.00
28.46
28.98
19.78
73.59
30.80
20.06
77.55
77.61
28.39
29.22
20.24
74.49
30.67
20.28
29.73
30.24
21.00
19.83
20.30
C(5)
C(6)
118.04
145.88
124.63
149.20
124.79
149.21
125.12
148.90
124.54
148.45
148.54
126.34
122.51
124.75
148.46
124.83
149.07
149.16
126.67
122.99
124.71
148.92
C(7)
C(8)
123.05
121.76
121.80
145.06
119.10
119.21
39.53
39.79
31.40
32.30
26.05
26.16
125.28
125.42
131.66
131.95
27.02
19.94
20.38
11.70
12.22
12.28
12.65
18.05
18.13
126.59
122.97
126.54
122.90
126.58
122.85
126.54
122.62
126.42
122.69
C(9)
C(10)
140.52
117.55
140.46
117.19
140.73
118.82
140.22
116.97
117.06
42.16
42.25
27.67
27.88
65.38
140.49
116.74
140.57
117.53
117.56
39.61
140.37
117.07
C(1´)
C(2´)
C(3´)
C(4´)
C(5´)
39.57
39.81
31.63
32.71
25.52
25.60
125.75
37.90
22.15
41.72
32.08
40.01
29.75
38.12
59.96
35.87
26.59
62.64
26.70
27.42
31.21
31.33
63.04
63.15
124.34
131.27
25.56
202.01
202.03
202.32
131.26
131.48
26.42
19.63
20.08
11.77
11.96
12.59
C(6´)
2-Me
25.56
21.81
19.09
20.07
11.43
11.63
12.50
13.83
20.40
20.45
11.75
11.99
12.85
23.65
Me—Ar
11.70
11.96
12.82
11.93
12.16
12.97
11.52
11.72
12.58
11.59
11.81
12.67
1´-Me
4´-Me
13.37
14.15
13.66
14.84
13.55
14.26
17.42
19.35
20.01
5´-Me
Ac
14.77
17.59
CO
CH3
169.57
20.39
169.57
20.39
169.73
20.59
169.23
20.07
169.28
20.13
169.67
20.45
169.80
20.17
20
(10 : 1) gave 1.16 g (54%) of chromans 3; according to GLC,
this was a 1 : 1 mixture of erythro- and threo-diastereomers;
[α]D –2.0° (c 3.0, CHCl3). UV (CHCl3), λmax/nm (ε): 296
mixture of erythro- and threo-diastereomers of 4; [α]D –5.7°
(c 0.34, CHCl3). Found (%): C, 77.27; H, 9.63. C23H34O3.
Calculated (%): C, 77.10; H, 9.50. IR, ν/cm–1: 1740 (C=O).
UV (EtOH), λmax/nm (ε): 285 (2400). 1H NMR, δ: 0.97 (d,
1.5 H, C(1´)CH3, J = 7.0 Hz); 1.03 (d, 1.5 H, C(1´)CH3,
J = 7.0 Hz); 1.99 (s, 3 H, C(2)CH3); 1.6—2.0 (m, 7 H, H(3),
H(1´), H(2´), H(3´)); 1.62, 1.75 (both s, 6 H, C(5´)CH3,
H(6´)); 2.02 (s, 3 H, ArCH3); 2.06 (s, 3 H, ArCH3); 2.18 (s,
3 H, ArCH3); 2.38 (s, 3 H, OAc); 2.60 (t, 2 H, H(4)); 5.17 (t,
1 H, H(4´), J = 6.7 Hz).
20
(3780) (cf. Ref. 4). 1H NMR, δ: 1.02 (d, 1.5 H, C(1´)CH3,
J = 6.7 Hz); 1.08 (d, 1.5 H, C(1´)CH3, J = 6.8 Hz); 1.22 (s,
3 H, C(2)CH3); 1.6—2.1 (m, 7 H, H(3), H(1´), H(2´),
H(3´)); 1.66, 1.70, 1.72, 1.80 (all s, 6 H, C(5´)CH3, H(6´));
2.18 (s, 3 H, ArCH3); 2.22 (s, 3 H, ArCH3); 2.24 (s, 3 H,
ArCH3); 2.68 (t, 2 H, H(4), J = 6.6 Hz); 4.50 (s, 1 H, OH);
5.13 (t, 0.5 H, H(4´), J = 7.5 Hz); 5.26 (t, 0.5 H, H(4´),
J = 7.5 Hz).
6-Acetoxy-2,5,7,8-tetramethyl-2-(4-methylpent-3-en-1-
yl)chroman (7) and 7-acetoxy-1,1,4a,5,6,8-hexamethyl-
6-Acetoxy-2,5,7,8-tetramethyl-2-[2S-(6-methylhept-5-en-
2-yl)]chromans (4). A solution of chroman mixture 3 (0.5 g,
1.58 mmol) in 4 mL of Àñ2O and 5 mL of anhydrous Py was
kept for 0.5 h at ∼20 °C and then poured into 20 mL of ice
water and extracted with EtOAc. The extract was washed with
3 M HCl, a saturated solution of NaHCO3, and H2O, dried
with MgSO4, and concentrated to give 0.5 g (88.3%) of a
1,2,3,4-tetrahydro-9H-xanthene (8). Alcohol
2 (1.63 g,
10.56 mmol) was added dropwise (Ar, 98 °C) to a suspension
of TMHQ (0.8 g, 5.28 mmol) and the powdered Tseokar-10
catalyst (1.8 g) in 24 mL of boiling anhydrous n-heptane. The
reaction mixture was refluxed for 6 h, cooled to ∼20 °C, and
filtered. The filtrate was concentrated and the residue (1.9 g)

2230
Russ.Chem.Bull., Int.Ed., Vol. 50, No. 11, November, 2001
Odinokov et al.
20
was chromatographed on SiO2 as described above in the
synthesis of 3 to give a mixture of chromanols 5 and 6 (1.12 g)
(2 : 1, GLC data, retention times 20.89 and 22.02 min,
respectively). The mixture of 5 and 6 was dissolved in 11 mL
of anhydrous Py and 8.5 mL of Ac2O was added with stirring.
The mixture was kept for 0.5 h at ∼20 °C and poured into
25 mL of ice water, the products were extracted with EtOAc,
washed with 3 M HCl, a solution of NaHCO3, and H2O, and
dried with MgSO4 to give 1.20 g (68.9%) of a mixture of
acetates 7 and 8 (2 : 1, GLC data, retention times 21.45 and
22.76 min, respectively). The mixture was resolved by prepara-
give 0.08 g (58%) of alcohol 13, [α]D –5.8° (c 0.37, CHCl3).
Found (%): C, 71.97; H, 8.90. C20H30O4. Calculated (%):
C, 71.82; H, 9.04. IR, ν/cm–1: 3400 (OH), 1740 (C=O).
UV (CHCl3), λmax/nm (ε): 280 (2100), 288 (2500). 1H NMR,
δ: 0.94, 1.0 (both d, 3 H, C(1´)CH3, J = 6.5 Hz); 1.15 (s, 3 H,
C(2)CH3); 1.6—2.0 (m, 7 H, H(3), H(1´), H(2´), H(3´)); 2.0,
2.07, 2.13 (all s, 9 H, ArCH3); 2.34 (C, 3 H, CH3CO), 2.58 (t,
2 H, H(4), J = 6.6 Hz); 3.60, 3.65 (both t, 2 H, H(4´),
J = 6.1 Hz).
6-Acetoxy-2-(3-hydroxypropyl)-2,5,7,8-tetramethyl-
chroman (14). The reaction of aldehyde 12 (0.32 g, 1.04 mmol)
and NaBH4 (0.04 g, 1.04 mmol) in 3 mL of MeOH carried out
as described above gave 0.18 g (58%) of alcohol 14. IR,
ν/cm–1: 3400 (OH), 1740 (CH3CO). UV (CHCl3), λmax/nm (ε):
280 (1500), 287 (1700). 1H NMR, δ: 1.25 (s, 3 H, C(2)CH3);
1.65 (m, 4 H, H(1´), H(2´)); 1.78 ( m, 2 H, H(3)); 1.98, 2.02,
2.10 (all s, 9 H, ArCH3); 2.32 (s, 3 H, CH3CO); 2.59 (t, 2 H,
H(4), J = 6.6 Hz); 3.60 (m, 3 H, H(3´), OH).
tive GLC.
–1
Acetate 7. IR, ν/cm
: 1740 (C=O). UV (EtOH),
λ
max/nm (ε): 285 (1900), (cf. Ref. 6). 1H NMR, δ: 1.30 (s,
3 H, (C(2)CH3); 1.65, 1.73 (both s, 6 H, (C(4´)CH3, H(5´));
1.70—1.95 (m, 6 H, H(3),H(1´), H(2´)); 2.02, 2.08, 2.15
(all s, 9 H, ArCH3)); 2.38 (s, 3 H, CH3CO); 2.68 (t, 2 H,
H(4), J = 6.7 Hz); 5.19 (t, 1 H, H(3´), J = 7.0 Hz).
Acetate 8. m.p. 138—139 °C. IR, ν/cm–1: 1740 (C=O).
UV (EtOH), λmax/nm (ε): 285 (1700) (cf. Ref. 6). 1H NMR, δ:
0.95, 1.03 (both s, 6 H, C(4´)CH3); 1.19 (s, 3 H, C(2)CH3);
1.3—1.8 (m, 6 H, H(1´), H(2´), H(3´)); 2.10 (m, 1 H, H(3));
2.01, 2.03, 2.10 (all s, 9 H, ArCH3); 2.38 (s, 3 H, OAc); 2.61
(dd, 2 H, H(4), J = 5.1 and J = 16.0 Hz) (cf. Ref. 7).
References
1. T. Rosenau and W. D. Habicker, Tetrahedron, 1995, 51,
7919; M. Kouma, T. Takagi, A. Ando, and I. Kumadaki,
Chem. Pharm. Bull., 1995, 43, 1466; T. Rosenau, W. D.
Habicker, and C. L. Chen, Heterocycles, 1996, 43, 787;
T. Fujishima, H. Kagechika, and K. Shudo, Arch. Pharm.,
1996, 329, 27; T. Rosenau and W. D. Habicker, Tetra-
hedron Lett., 1997, 38, 5959.
2. V. N. Odinokov, A. Yu. Spivak, G. A. Emel´yanova, E. V.
Syutkina, Z. I. Ushakova, and L. M. Khalilov, Izv. Akad.
Nauk, Ser. Khim., 2000, 1631 [Russ. Chem. Bull., 2000, 49,
1620 (Engl. Transl.)].
6-Acetoxy-2,5,7,8-tetramethyl-2-[(2S-(5-oxopent-2-
yl)]chroman (11). An ozone—oxygen mixture was passed for
8 min through a mixture of acetates 4 (0.5 g, 1.4 mmol),
Ba(OH)2 (0.48 g, 2.8 mmol), H2O (0.12 mL), and acetone
–1
(5 mL) at ∼20 °C at a velocity of 30 L h (1.45 mmol of O3).
After the reaction was completed, the precipitate was filtered
off and the filtrate was concentrated in vacuo. The residue was
dissolved in 10 mL of Et2O, dried with MgSO4, and concen-
trated. The residue was chromatographed on SiO2 using an
3. H. Mayer and O. Isler, Methods in Enzymology, 18, Vitamins
and Coenzymes, Part C, Acad. Press, New York—London,
1971, 271 pp.
n-hexane—Et2O mixture (10 : 1) as the eluent to give 0.24 g
20
(52%) of aldehyde 11, [α]D
–5.9° (c 0.54, CHCl3).
Found (%): C, 72.47; H, 8.50. C20H28O4. Calculated (%): C,
72.26; H, 8.49. IR, ν/cm–1: 1710 and 1740 (C=O). UV
(CHCl3), λmax/nm (ε): 280 (1400), 288 (1600). 1H NMR, δ:
0.92, 0.98 (both d, 3 H, C(1´)CH3, J = 6.9 Hz, J = 6.7 Hz);
1.15 (s, 3 H, C(2)CH3); 1.6—2.0 (m, 5 H, H(3), H(1´),
H(2´)); 1.98, 2.00, 2.10 (all s, 9 H, ArCH3); 2.30 (s, 3 H,
CH3CO); 2.58 (m, 4 H, H(4), H(3´)); 9.80 (s, 1 H, H(4´)).
6-Acetoxy-2,5,7,8-tetramethyl-2-(3-oxopropyl)chroman
(12). An ozone—oxygen mixture was passed for 15 min through
a mixture of acetates 7 and 8 (0.8 g) (the content of 7 in the
mixture was 0.48 g (1.45 mmol)), Ba(OH)2 (0.87 g, 5.04 mmol),
4. E. V. Kuzakov and E. N. Shmidt, Khimiya Prirod. Soedin.,
2000, 198 [Chem. Nat. Compd., 2000 (Engl. Transl.)].
5. M. H. Stern, T. H. Regan, D. P. Maier, C. D. Robeson,
and J. G. Thweatt, J. Org. Chem., 1973, 38, 1264.
6. E. I. Zakharova, K. A.-V. Shuaipov, V. V. Chudinova,
S. M. Alekseev, and R. P. Evstigneeva, Bioorgan. Khim.,
1989, 15, 1268 [Sov. Bioorg. Chem., 1989, 15 (Engl.
Transl.)]; V. V. Chudinova, E. I. Zakharova, S. M. Alekseev,
K. A.-V. Shuaipov, and R. P. Evstigneeva, III Vsesoyuz.
konf. "Bioantioksidant" (III All-Union Conf. "Bioanti-
oksidant"), Abstrs., Moscow, 1989, 1, 230 (in Russian).
7. T. Ichikawa and T. Kato, Bull. Chem. Soc. Jpn., 1968,
41, 1224.
8. M. Matsui and H. Yamamoto, Bull. Chem. Soc. Jpn., 1995,
68, 2663.
9. V. N. Odinokov, V. R. Akhmetova, Kh. D. Khasanov,
A. A. Abduvakhabov, V. R. Sultanmuratova, and G. A.
Tolstikov, Zh. Org. Khim., 1992, 28, 1173 [Russ. J. Org.
Chem., 1992, 28 (Engl. Transl.)]
H2O (0.2 mL), and acetone (8 mL) at ∼20 °C at a velocity of
–1
30 L h
(2.05 mmol of O3). The reaction mixture was
worked-up as described in the previous experiment to give
0.35 g (80%) of aldehyde 12 and 0.25 g of compound 8.
–1
Aldehyde 12. IR, ν/cm
: 1710 and 1740 (C=O).
UV (CHCl3), λmax/nm (ε): 278 (1600), 287 (1800). 1H NMR,
δ: 1.20 (s, 3 H, C(2)CH3); 1.75 (m, 4 H, H(3), H(1´)); 1.95,
2.0, 2.03 (all s, 9 H, ArCH3); 2.10 (s, 3 H, CH3CO); 2.58
(m, 4 H, H(4), H(2´)); 9.75 (s, 1 H, H(3´)).
10. I. E. Pokrovskaya, A. T. Menyailo, M. V. Pospelov, A. K.
Ryzhankova, A. G. Shil´nikova, G. N. Dudnik, and L. S.
Mishina, Neftekhimiya, 1970, 10, 554 [Petroleum Chemis-
try, 1970, 10 (Engl. Transl.)].
11. S. Brownstein, G. W. Burton, L. Hughes, and K. U.
Ingold, J. Org. Chem., 1989, 54, 560.
6-Acetoxy-2-[2S-(5-hydroxypent-2-yl)]-2,5,7,8-tetra-
methylchroman (13). NaBH4 (0.017 g, 0.42 mmol) was added
in one portion to a solution of aldehyde 11 (0.14 g, 0.4 mmol)
in 2 mL of MeOH. The reaction mixture was stirred for 12 h
and then the solvent was removed in vacuo. The residue was
dissolved in EtOAc, washed with 3 M HCl, a saturated solu-
tion of NaHCO3, and brine, and dried with MgSO4. The
solution was concentrated and the residue was chromatographed
on SiO2 using a 10 : 1 hexane—EtOAc mixture as the eluent to
Received March 7, 2001;
in revised form April 24, 2001