Synthesis of 10-carbonyl and 10-carboxylic derivatives of para-mentha-1,8-diene-5,6-diol

Article abstract of DOI:10.1007/s10600-015-1320-x

The synthesis of 10-carbonyl and 10-carboxylic derivatives of para-mentha-1,8-diene-5,6-diol (1) that exhibited high anti-Parkinson's activity was described. The synthesis of these compounds was an important programmatic component in a study of the metabo

Full text of DOI:10.1007/s10600-015-1320-x

DOI 10.1007/s10600-015-1320-x
Chemistry of Natural Compounds, Vol. 51, No. 3, May, 2015
SYNTHESIS OF 10-CARBONYL AND 10-CARBOXYLIC
DERIVATIVES OF para-MENTHA-1,8-DIENE-5,6-DIOL
1,2*
1
1,2
O. V. Ardashov,
D. V. Korchagina, K. P. Volcho,
1,2
and N. F. Salakhutdinov
The synthesis of 10-carbonyl and 10-carboxylic derivatives of para-mentha-1,8-diene-5,6-diol (1) that
exhibited high anti-Parkinson’s activity was described. The synthesis of these compounds was an important
programmatic component in a study of the metabolism of 1.
Keywords: para-mentha-1,8-diene-5,6-diol, anti-Parkinson’s activity, metabolites, oxidation, carbonyl derivative,
lactone.
Our previous discovery [1, 2] that (4S,5R,6R)-para-mentha-1,8-diene-5,6-diol (1) exhibited high anti-Parkinson’s
activity stimulated further studies of it. The absolute configuration of 1 affected its anti-Parkinson’s activity [1]. It was
important to include all functional groups (double bonds and hydroxyls) in the molecule [3]. Metabolism studies represent a
key phase of pharmacokinetic investigations. As a rule, mass spectra of monoterpenoids are very difficult to relate reliably to
their structures without mass spectrometric data of the pure compounds, which makes it necessary to synthesize them.
7
1
OH
OH
OH
OH
3
9
5
OH
OH
OH
O
10
1
2
3
According to literature data on the metabolism of para-menthane monoterpenoids [4–7], the formation of products
from methyl hydroxylation and further oxidation to carbonyl compounds were expected. We synthesized earlier hydroxy-
derivatives 2 [8] and 3 [9]. The methods for synthesizing these and other similar alcohols were recently reviewed by us in
detail [10].
The goal of the present work was to synthesize 10-carbonyl and 10-carboxylic derivatives of 1.
The first task was to prepare 2-[(1S,5R,6R)-5,6-dihydroxy-4-methylcyclohex-3-enyl]acrylaldehyde (3). The simplest
approach seemed to involve oxidation of triol 2. However, its reaction with MnO formed reaction mixtures with <30% of
2
target aldehyde 3 according to PMR and GC-MS data.
We used bromide 4 as a key intermediate in the synthesis of triol 2 [8]. Also, bromides are known to be capable of
transforming into the corresponding aldehydes via alkylation of nitro compounds followed by Nef hydrolysis [11, 12] or
Kornblum oxidation by DMSO–NaHCO [13, 14]. However, instead of the expected reaction with EtNO , 4 underwent an
3
2
intramolecular heterocyclization to form bicyclic product 5 in quantitative yield (Scheme 1). We prepared previously 5 in
15% yield via the reaction of 4 with n-BuLi [8]. Thus, the newly found version for performing the intramolecular cyclization
turned out to be much more effective. Kornblum oxidation of 5 via reaction with DMSO in CCl formed a complicated
4
product mixture with total contents of identified 3 and 5 of <7%.
1) N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences,
Russian Federation, 630090, Novosibirsk, Prosp. Lavrentꢀeva, 9, fax: (383) 330 97 52, e-mail: ardashov@nioch.nsc.ru;
2) Novosibirsk National Research State University, Russian Federation, 630090, Novosibirsk, Ul. Pirogova, 2. Translated
from Khimiya Prirodnykh Soedinenii, No. 3, May–June, 2015, pp. 419–423. Original article submitted October 28, 2014.
©
0009-3130/15/5103-0483 2015 Springer Science+Business Media New York
483

OH
OH
H
a
b
3 + 5 + . . .
OH
Br
O
H
4
5
a. DMSO, NaHCO or i-Pr NEt, CCl , reflux 3 h; b. EtNO , NaOH, i-PrOH, H O, THF, 40–50ꢁC, 1 h
3
2
4
2
2
Scheme 1
Therefore, protected triol 2 should be used to develop approaches to the synthesis of aldehyde 3. Compound 4 is
known to react smoothly with NaOAc to form the primary acetate 6 [8], which we also used further as starting material.
The reaction of 6 with dihydropyran in the presence of pyridinium p-toluenesulfonate (PPTS) followed by saponification
produced bis-THP derivative 7 as a set of four stereomers at the THP groups in equal ratios with 88% overall yield (Scheme 2).
Oxidation of stereomers 7 by MnO produced a set of four aldehyde diastereomers 8 in overall 75% yield.
2
10
O
O
O 16
OH
3
3
3
19
19
O 16
OH
1.
2. b
, a
17
c
d
O
1
5
5
8
5
13
1
OH
O
1
O
O
OH
OAc
11 O
11 O
O
OH
7
8
15
7
9
15
7
8
9
9
6
7, 88%
8, 75%
3, 67%
a. PPTS, CH Cl , 3 d; b. NaOH, MeOH, H O, 24 h; c. MnO , CCl , 16 h; d. p-TsOH, H O, dioxane, 20 h
2
2
2
2
4
2
Scheme 2
The tetrahydropyranyl protection is usually removed in aqueous MeOH in the presence of various acid catalysts such
as PPTS [15] and p-TsOH [16]. Very effective methods for adding and removing pyranyl protection using In(OTf) [17] and
3
(NH ) Ce(NO ) (CAN) [18] as catalysts were described. Use of In(OTf) , CAN, or PPTS in various solvents to remove THP
4 2
3 6
3
from stereomers 9 was accompanied by secondary and/or side reactions and formed complicated product mixtures. Use of
p-TsOH in aqueous dioxane turned out unexpectedly to be the most effective method for removing THP in this instance. The
reaction was carried out for 20 h in diluted solvent with a total reagent concentration of <1%. As a result, the desired aldehyde
3 was obtained in 67% yield (Scheme 2). Increasing the total reagent concentration by decreasing the amount of solvent
decreased significantly the yield of 3, the overall yield of which for all steps starting from acetate 6 was 44%.
Finding a suitable method for oxidizing an aldehyde to a carboxylic group in complicated multi-functional compounds
is often a daunting task. The Corey method that uses NaCN and MnO [19, 20], oxidation using Ag O [21–23], use of
2
2
NaClO –NaH PO –trimethylethylene [20, 24–26], and oxidation by Ru compounds [27] and CAN–t-BuOOH [28] must be
2
2
4
mentioned among several well-recommended approaches.
The Corey method consisting of oxidation of the cyanohydrin formed via reaction of the aldehyde with NaCN can be
complicated by Michael addition in the presence of activated double bonds. Therefore, we did not attempt it. A mixture of
hemiacetals instead of the expected carboxylic products resulted from oxidation of 3 by CAN–t-BuOOH.
Next, we elaborated various methods based on Ag O, namely, by varying the temperature and reaction time, and used
2
various bases (NaOH, NH , TMEDA, NEt , DMAP). Aqueous EtOH and aqueous dioxane were used as solvents. The best
3
3
conditions for oxidizing 3 turned out to be NaOH as the base for the reaction carried out in aqueous dioxane for 12 h at room
temperature. This produced lactone 9 in 21% yield (Scheme 3). The overall yield of 9 was 9.3% over the four steps starting
from acetate 6.
3
OH
8 O
OH
OH
1
a
5
+
OH
O
OH
O
7
O
9
OH
10
3
9, 21%
a. Ag O, NaOH, H O, dioxane, 12 h
2
2
Scheme 3
484

Moreover, a small amount of a mixture of lactone 9 and acid 10 was isolated from the reaction mixture. The GC-MS
with the corresponding mass spectrum of 10 and retention times were recorded for the mixture, i.e., data required for metabolism
studies were obtained.
Thus, a synthesis of 10-carbonyl and 10-carboxylic derivatives of 1, its proposed metabolites, was developed. The
synthesis was based on 10-acetoxy derivative 6 using THP protection during the oxidation by MnO and Ag O.
2
2
EXPERIMENTAL
13
PMR and C NMR spectra were recorded from CDCl or CDCl –CCl mixtures (~1:1, v/v) on a Bruker DRX-500
3
3
4
1
13
spectrometer (operating frequency 500.13 MHz for H and 125.76 MHz for C). Residual CD(H)Cl resonances (ꢂ 7.24;
3
H
ꢂ 76.90 ppm) were used as standards. The structures of the synthesized compounds were established by analyzing PMR
C
1
1
13
13
1
spectra, H– H double resonance spectra, C NMR spectra recorded in J-modulation mode (JMOD), and C– H 2D
heteronuclear correlation spectra over direct and through-space SSCC (C–H COSY, J
1
2,3
= 135 Hz; COLOC,
J
= 10 Hz,
C,H
C,H
respectively). High-resolution mass spectra were taken on a DFS Thermo Scientific spectrometer with full scanning in the
range 0–500 m/z and electron-impact ionization at 70 eV with direct sample introduction. Specific optical rotation [ꢃ] was
D
determined on a polAAr 3005 polarimeter. Gas chromatography used a 7820A GC (Agilent Tech., USA) with a flame-
ionization detector, HP-5 capillary column (0.25 mm # ꢄ 30 m ꢄ 0.25 ꢅm), and He carrier gas (flow rate 2 mL/min). GC-MS
was recorded on an Agilent 7890A chromatograph with an Agilent 5975C quadrupole mass detector and HP-5MS quartz
column (0.25 mm # ꢄ 30 m ꢄ 0.25 ꢅm). Solvents were purified by standard methods.
(3aS,7R,7aR)-6-Methyl-3-methylene-2,3,3a,4,7,7a-hexahydrobenzofuran-7-ol (5). NaOH (47 mg, 1.18 mmol)
was dissolved in a mixture of H O (0.7 mL), i-PrOH (1.5 mL), and THF (0.7 mL), treated with EtNO (0.017 mL, 0.24 mmol),
2
2
heated to 40°C, treated with a solution of (1R,2R,6S)-6-(3-bromoprop-1-en-2-yl)-3-methylcyclohex-3-ene-1,2-diol (4, 50 mg,
0.20 mmol) in THF (2 mL), stirred for 1 h at 40-50°C, treated with H O (10 mL), and extracted with Et O (3 ꢄ 5 mL). The
2
2
combined organic phase was washed with saturated NaHCO solution, dried over Na SO , and evaporated to afford 5 (34 mg,
3
2
4
0.20 mmol, quantitative). The PMR spectrum of 5 agreed with that published earlier [8].
2-[(1S,5R,6R)-4-Methyl-5,6-bis(tetrahydro-2H-pyran-2-yloxy)cyclohex-3-enyl]prop-2-en-1-ol (7). A solution
of p-TsOHꢄH O (52 mg, 0.274 mmol), Py (26 mg, 0.329 mmol), and 3,4-dihydro-2H-pyran (0.309 g, 3.68 mmol) in CH Cl
2
2
2
(2 mL) was treated with a solution of 6 (150 mg, 0.721 mmol) in CH Cl (8 mL) and left for 3 d. The solvent was distilled
2
2
off. The solid (0.546 g) was purified by flash chromatography over silica gel (9 g, 60–200 ꢅ, Macherey-Nagel) with elution by
hexane. The solvent was distilled off. The solid (0.286 g) was dissolved in MeOH (30 mL), treated with a solution of NaOH
(0.628 g, 15.7 mmol) in H O (3 mL), left for 24 h, and treated with H O (10 mL). The MeOH was distilled off. The solution
2
2
was extracted with EtOAc (3 ꢄ 20 mL). The extract was dried over Na SO and evaporated. The solid (0.253 g) was purified
2
4
by flash chromatography over silica gel (9 g, 60–200 ꢅ, Macherey-Nagel) with elution by hexane and EtOAc to afford 7
(222 mg, 0.631 mmol, 88% calculated for 6) as a mixture of four diastereomers (1:1:1:1, two additional asymmetric centers 11
1
and 16). Í NMR spectrum (CDCl + ÑÑl (1:1), ꢂ, ppm, J/Hz): 1.72 (3H, m), 1.74 (3H, m), 1.78 (3H, m) and 1.80 (3H, m)
3
4
– all J 2.5 Hz – 12H-10, 1.86–2.02 (4H, m, 4H-5e), 2.30–2.43 (4H, m, 4H-5a), 2.56 (1H, br.dd, J
= 11.8, J
= 5.1) and
6a,5a
6a,5e
2.62–2.69 (3H, m) – 4H-6a, 3.35–3.56 (8H, m) and 3.77–4.00 (8H, m) – 8H-15 and 8H-20, 3.67 (1H, br.d, J
= 2.8), 3.85
2e,1e
(1H, br.d, J
= 3.1), 3.97 (1H, br.d, J
= 2.2), 4.16 (1H, dd, J
= 2.8) and 4.11 (1H, br.d, J
= 2.8) – 4H-2e, 3.81 (1H, m), 4.01 (1H, dd,
2e,1e
2e,1e
2e,1e
J
= 3.1, J
= 2.8, J
= 1.9) and 4.32 (1H, dd, J
= 2.8, J
= 2.1) – 4H-1e, 4.00–4.24
1e,6a
1e,2e
1e,6a
1e,2e
1e,6a
1e,2e
(8H, m, 8H-9), 4.59–4.77 (8H, m, 4H-11, 16), 4.94 (1H, br.s), 4.97 (1H, br.s), 4.99–5.01 (2H, m), 5.07 (1H, m, all J 2.0), 5.10
(1H, m, all J 2.0) and 5.13–5.16 (2H, m, all J 2.0) – 8H-8), 5.62–5.70 (4H, m, 4H-4), 1.43–1.87 (m, other protons).
13
C NMR spectrum (CCl –CDCl (1:1 v/v), ꢂ, ppm): 74.66, 75.17, 77.04, 78.10 (4 d, 4C-1), 73.20, 75.38, 77.54, 79.75 (4 d,
4
3
4C-2), 130.23, 130.54, 130.70, 130.94 (4 s, 4C-3), 126.07, 126.09, 126.11, 126.23 (4 d, 4C-4), 25.31, 25.45, 25.64, 25.96
(4 t, 4C-5), 36.13, 36.76, 37.63, 38.14 (4 d, 4C-6), 149.74, 149.92, 149.96, 150.07 (4 s, 4C-7), 111.42, 111.55, 113.52, 113.69
(4 t, 4C-8), 65.36, 65.57, 65.68, 65.77 (4 t, 4C-9), 21.15, 21.23, 21.28, 21.33 (4 q, 4C-10), 96.91, 97.35, 97.74, 97.87, 100.26,
100.56, 101.66, 102.22 (8 d, 4C-11, 16), 30.60, 30.78, 31.18, 31.21, 31.25, 31.27, 31.47, 31.48 (8 t, 4C-12 and 4C-17), 19.51,
19.72, 19.74, 19.93, 20.00, 20.32, 20.42, 20.48 (8 t, 4C-13, 18), 25.26, 25.34, 25.41, 25.44, 25.47, 25.48, 25.53, 25.55 (8 t,
+
4C-14, 19), 62.22, 62.33, 62.62, 62.84, 62.96, 63.36, 63.57, 63.65 (8 t, 4C-15, 20). Found: m/z 250.1559 [M – C H O ] .
5
10
2
+
Ñ Í Î . Calcd [M – C H O ] : 250.1563.
10 16
3
5 10 2
485

2-[(1S,5R,6R)-4-Methyl-5,6-bis(tetrahydro-2H-pyran-2-yloxy)cyclohex-3-enyl]acrylaldehyde (8). Asuspension
of MnO (3.01 g, 34.6 mmol) in CCl (25 mL) was treated with a solution of 7 (207 mg, 0.588 mmol) in CCl (20 mL) and
2
4
4
stirred for 16 h at room temperature. The precipitate was filtered off. The solvent was distilled off. The solid was purified by
flash chromatography over silica gel (9 g, 60–200 ꢅ, Macherey-Nagel) with elution by hexane and EtOAc (10%) in hexane to
afford 8 (155 mg, 0.443 mmol, 75%) as a mixture of four diastereomers (1:1:1:1, two additional asymmetric centers 11 and
1
16). Í NMR spectrum (CDCl + ÑÑl (1:1), ꢂ, ppm, J/Hz): 1.72 (3H, m), 1.73 (3H, m), 1.80 (3H, m) and 1.82 (3H, m) – all
3
4
J
2.5 – 12H-10, 1.86–1.96 (4H, m, 4H-5e), 2.21–2.37 (4H, m, 4H-5a), 3.04–3.19 (4H, m, 4H-6a), 3.29–3.54 (m), 3.67–3.85
(m) and 3.94–4.03 (m) – 16H, 8H-15, 20, 3.66 (1H, br.s, H-2e), 3.82 (1H, br.d, J = 3.0, H-2e), 4.01 (1H, br.d, J = 2.8,
2e,1e
2e,1e
H-2e), 4.05 (1H, br.d, J
= 2.8, H-2e), 3.74 (1H, dd, J
= 3.0, J
= 1.8, H-1e), 3.92–3.94 (2H, m, 2H-1e), 4.16 (1H, dd,
2e,1e
1e,2e
1e,6a
J
= 2.8, J
= 2.0, H-1e), 4.38 (1H, dd, J = 4.5, 3.1), 4.49 (1H, dd, J =4.8, 3.1), 4.54 (1H, dd, J = 5.0, 2.8), 4.62 (1H, dd,
1e,2e
1e,6a
J = 5.5, 2.7), 4.72 (1H, dd, J = 4.3, 2.8), 4.77 (1H, dd, J = 3.5, 2.7), 4.81 (1H, dd, J = 3.8, 3.0), 4.83 (1H, dd, J = 3.5, 2.8) – 4H-11,
16, 5.59–5.69 (4H, m, 4H-4), 6.03 (1H, m), 6.04 (1H, br.s), 6.06 (1H, br.s), 6.07 (1H, br.s), 6.30 (1H, m), 6.36 (1H, m), 6.41
13
(1H, m), 6.51 (1H, m), all J 2.0, 8H-8, 9.52 (3H, s) and 9.53 (1H, s) – 4H-9, 1.36–1.87 (m, other protons). C NMR
spectrum, (CCl – CDCl (1:1 v/v), ꢂ, ppm): 70.86, 74.03, 75.64, 78.66 (4 d, 4C-1), 71.98, 74.73, 76.43, 78.34 (4 d, 4C-2),
4
3
130.79, 130.85, 131.25, 131.52 (4 s, 4C-3), 124.87, 125.11, 125.24, 125.63 (4 d, 4C-4), 24.68, 24.86, 24.99, 25.66 (4 t, 4C-5),
30.75, 31.01, 31.33, 31.35 (4 d, 4C-6), 151.05, 151.09, 151.35, 151.66 (4 s, 4C-7), 134.41, 134.62, 134.62, 134.95 (4 t, 4C-8),
193.53, 193.69, 193.80, 193.82 (4 d, 4C-9), 21.23, 21.26, 21.39, 21.52 (4 q, 4C-10), 96.26, 96.40, 97.36, 97.47, 100.61,
100.79, 100.99, 101.09 (8 d, 4C-11, 16), 30.57, 30.58, 30.62, 30.89, 30.92, 30.95, 31.00, 31.32 (8 t, 4C12, 17), 18.91, 19.18,
19.50, 19.69, 19.73, 19.82, 19.91, 19.95 (8 t, 4C-13, 18), 25.37, 25.38, 25.40, 25.42, 25.52, 25.52, 25.61, 25.62 (8 t, 4C-14,
19), 61.63, 61.78, 62.33, 62.36, 62.52, 62.64, 62.92, 63.28 (8 t, 4C-15, 20).
2-[(1S,5R,6R)-5,6-Dihydroxy-4-methylcyclohex-3-enyl)acrylaldehyde (3). A solution of p-TsOHꢄH O (0.500 g,
2
2.63 mmol) in H O (10 mL) was treated with a solution of 8 (0.134 g, 0.383 mmol) in dioxane (60 mL) and stirred for 20 h at
2
room temperature. The dioxane was distilled off. NaHCO (0.35 g, 4.17 mmol) and saturated NaCl solution (10 mL) were
3
added in portions. The mixture was extracted with EtOAc (4 20 mL). The combined organic phase was dried over Na SO .
2
4
The solvent was distilled off. The solid was separated by column chromatography over silica gel (17 g, 60–200 ꢅ, Macherey-
24
Nagel) with gradient elution by EtOAc (0–100%) in hexane to afford 3 (46.9 mg, 0.258 mmol, 67%). [ꢃ] –30.0° (c 0.367,
D
1
2
CHCl ). Í NMR spectrum (CDCl , ꢂ, ppm, J/Hz): 1.81 (3H, m, all J 2.5, H-10), 2.09 (1H, dddq, J = 17.7, J
= 5.6,
3
3
5e,6a
2
J
= 4.5, J
C -OH), 3.10 (1H, dddd, J
= 1.5, H-5e), 2.23 (1H, dddqd, J = 17.7, J
= 9.8, J
= 2.8, J
= 2.5, J = 1.1, H-5a), 2.43 (1H, br.s,
5e,4
1
5e,10
5a,6a
5a,4
5a,10
5a,2e
= 9.8, J
= 5.6, J
= 2.2, J
= 1.0, H-6a), 3.82 (1H, br.d, J
= 3.7, H-2e), 3.87 (1H,
6a,5a
6a,5e
6a,1e
6a,8’
2e,1e
dd, J
= 3.7, J
= 2.2, H-1e), 5.62 (1H, ddq, J
= 4.5, J
= 2.8, J
= 1.4, H-4), 6.16 (1H, s, H-8), 6.51 (1H, br.s,
1e,2e
1e,6a
4,5e
4,5a
4,10
13
H-8ꢀ), 9.54 (1H, s, H-9). C NMR spectrum (CDCl , ꢂ, ppm): 72.03 (d, C-1), 72.31 (d, C-2), 132.53 (s, C-3), 124.10 (d, C-4),
25.61 (t, C-5), 33.42 (d, C-6), 150.49 (s, C-7), 136.87 (t, C-8), 195.49 (d, C-9), 20.44 (q, C-10). Found: m/z 182.0937 [M] .
3
+
+
Ñ Í Î . Calcd [M] : 182.0938.
10 14
3
(3aS,7R,7aR)-7-Hydroxy-6-methyl-3-methylene-3a,4,7,7a-tetrahydrobenzofuran-2(3H)-one (9). A solution of
NaOH (0.242 g, 6.05 mmol) in H O (7 mL) was stirred, treated over 5 min with a solution of AgNO (0.332 g, 1.95 mmol),
2
3
stirred for 5 min, and decanted. The precipitate was washed with H O (3 ꢄ 15 mL), treated with a solution of NaOH (53.0 mg,
2
1.33 mmol) in H O (7 mL) and then a solution of 3 (16.6 mg, 91.2 ꢅmol) in dioxane (9 mL). The mixture was stirred for
2
12 h. The precipitate was filtered off. The solvent was distilled off to a volume of 3–4 mL. The solution was treated with
saturated NaCl solution (8 mL) and conc. HCl (0.8 mL) and extracted with CHCl (4 ꢄ 7 mL). The extracts were dried over
3
Na SO to afford a fraction (3.7 mg) containing 9 (MW 180.0777, C H O ) and 11 (MW 198.0877, C H O ) as the
2
4
10 12
3
10 14 4
principal components. The aqueous phase was saturated with NaCl, treated with conc. HCl (0.4 mL), and extracted with
EtOAc (2 ꢄ 20 mL). The extracts were dried over Na SO to afford another fraction (11.4 mg). Both fractions were combined
2
4
(15.1 mg) and separated by column chromatography over silica gel (1.0 g, 60–200 ꢅ, Macherey-Nagel) with gradient elution
26
1
by EtOAc (0–100%) in hexane to afford 9 (3.5 mg, 19.4 ꢅmol, 21%). [ꢃ] –184.6° (c 0.117, CHCl ). Í NMR spectrum
D
3
2
(CDCl , ꢂ, ppm, J/Hz): 1.82 (3H, m, all J 2.5, H-10), 2.02 (1H, dddq, J = 16.1, J
= 5.8, J
= 4.5, J
= 2.0, H-5e),
3
5e,4
5e,6a
5e,10
2
2.16 (1H, br.s, OH), 2.61 (1H, dddq, J = 16.1, J
= 7.8, J
= 5.4, J
= 1.4, H-5a), 3.24 (1H, ddddd, J
= 9.0,
= 5.8,
5a,6a
5a,4
5a,10
6a,1a
J
= 7.8, J
= 4.5, J
= 3.0, J
= 2.5, H-6a), 4.16 (1H, br.d, J
= 5.8, H-2), 4.55 (1H, dd, J
= 9.0, J
1a,6a 1a,2
6a,5a
6a,5e
6a,9’
6a,9
2,1a
H-1a), 5.60 (1H, d, J
= 2.5, H-9), 5.62 (1H, ddq, J
= 5.8, J
= 5.4, J
= 1.5, H-4), 6.27 (1H, d, J
= 3.0, H-9ꢀ).
9,6a
4,5e
4,5a
4,10
9ꢀ,6a
13
C NMR spectrum (CDCl , ꢂ, ppm): 82.07 (d, C-1), 71.53 (d, C-2), 136.59 (s, C-3), 121.72 (d, C-4), 27.84 (t, C-5), 35.42 (d,
C-6), 139.13 (s, C-7), 170.11 (s, C-8), 122.43 (t, C-9), 18.64 (q, C-10). Found: m/z 180.0777 [M] . Ñ Í Î . Calcd [M] :
3
+
+
10 12
3
180.0781.
486

ACKNOWLEDGMENT
We thank the Russian Federation Ministry of Education and Science for financial support.
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