Enantioselective synthesis of 11-homodrim-7-en-9α,12,13-triol

Article abstract of DOI:10.1007/s10600-011-9998-x

The enantioselective synthesis of 11-homodrim-7-en-9α,12,13-triol, a convenient synthon for preparing polyfunctional 11-homodrimane sesquiterpenoids, was carried out starting from norambreinolide, a cleavage product available from several bicyclic labdane diterpenoids.

Full text of DOI:10.1007/s10600-011-9998-x

Chemistry of Natural Compounds, Vol. 47, No. 4, September, 2011 [Russian original No. 4, July-August, 2011]
ENANTIOSELECTIVE SYNTHESIS OF 11-HOMODRIM-7-EN-9ꢀ,12,13-TRIOL
1*
1
1
1,2
P. F. Vlad, K. G. Edu, M. N. Koltsa, A. G. Chokyrlan,
UDC 547.91+547.057+547.15
2,3
2,3
A. Nikolescu, and K. Delyanu
The enantioselective synthesis of 11-homodrim-7-en-9ꢀ,12,13-triol, a convenient synthon for preparing
polyfunctional 11-homodrimane sesquiterpenoids, was carried out starting from norambreinolide, a cleavage
product available from several bicyclic labdane diterpenoids.
Keywords: synthesis, 11-homodrimane compounds, norambreinolide.
One of the main motivators for the unwavering interest of chemists in drimane sesquiterpenoids is their broad spectrum
of biological activity [1, 2]. Several syntheses of them have been developed because most of them are difficultly accessible
compounds and occur in trace quantities as complicated mixtures in natural sources [2–4]. However, many of the syntheses
are multi-step and inefficient. In addition, the starting compounds are not always readily available.
In contrast with drimane sesquiterpenoids, homodrimane (tetranorlabdane) compounds are more available because
they can be prepared by relatively simpler methods from readily available labdane diterpenoids (sclareol, larixol, abienols,
manool, manoyloxides, and zamoranic, communic, and labdanolic acids, etc.) [5].
The preparation of tetranorlabdane derivatives has been often reported. Several of these derivatives have been widely
applied in the perfume, cosmetic, and tobacco industries owing to their amber aroma. Judging from the literature, most
homodrimanes have not been tested for types of activity other than organoleptic. However, it was recently found that
11-homopolygodial (1) had antifeedant activity greater than that of natural polygodial (2) [6]. Therefore, it seemed interesting
to synthesize polyfunctional homodrimanes.
Herein results from the synthesis of 11-homodrim-7-en-9ꢀ,12,13-triol (3) from commercially available norambreinolide
(4) are reported.
Norambreinolide (4) was reduced by LiAlH by the literature method [7] to sclarodiol (5), which was identified by
4
comparison with an authentic sample. Diol 5 was acetylated under standard conditions by a mixture of acetic anhydride and
pyridine. According to TLC, the reaction products included the desired 12-monoacetate of sclarodiol (6) and an impurity of a
less polar compound that was separated by chromatography over a column of SiO (Scheme 1). Hydroxyacetate 6 was
2
identified by comparison with an authentic sample that was obtained by us earlier [8]. Its spectral properties agreed with those
published [9–10]. Reaction of 6 with triphenylphosphine and iodine by the literature method [11] formed a mixture of unsaturated
acetates 7, in which the isomer with the tetra-substituted double bond dominated (64%) according to NMR spectroscopy. The
contents of the isomers with the tri-substituted and exocyclic double bonds were 19 and 17%, respectively. Dehydration of 6
by phosphoryl chloride in pyridine afforded a product in which the isomer with the exocyclic double bond dominated [12].
The mixture of acetates 7 was oxidized by sodium chromate by the literature method [13] to 12-acetoxy-11-homodrim-8-en-
7-one (8) (60% yield).
Ketoacetate 8 was reacted with N-bromosuccinimide (NBS) in order to functionalize the C-13 methyl. This produced
12-acetoxy-13-bromo-11-homodrim-8-en-7-one (9) in high yield (80%) (Scheme 1). Its structure was confirmed by spectral
data (see Experimental). Compound 9 reacted smoothly with potassium acetate in DMF to substitute the Br by acetoxy and
form ketodiacetate 10 in good yield (80%). Saponification under mild conditions by K CO in MeOH under an inert atmosphere
2
3
produced ketodiol 11, which gave 8(9)-ꢀ-epoxy-11-homodrim-12,13-diol-7-one (12) upon oxidation by hydrogen peroxide in
the presence of sodium hydroxide in MeOH (Scheme 1).
1) Institute of Chemistry,Academy of Sciences of the Republic of Moldova, MD-2028 Kishinev, Republic of Moldova,
fax: (37322) 73 97 75, e-mail: pavel_f_vlad@yahoo.co.uk; 2) P. Poni Institute of Macromolecular Chemistry, Romanian
Academy of Sciences, 41-AGrigore Ghica VodaAlley, RO-700487 Iasi, Romania; 3) Institute of Organic Chemistry, Romanian
Academy of Sciences, Spl. Independentei 202-B, P. O. Box 35-98, Po-060023, Bucharest, Romania. Translated from Khimiya
Prirodnykh Soedinenii, No. 4, July–August, 2011, pp. 509–512. Original article submitted March 3, 2011.
©
574
0009-3130/11/4704-0574 2011 Springer Science+Business Media, Inc.

12
13
CHO
CHO
O
11
CHO
OAc
OH
OH
OH
16
9
CHO
O
a
1
b
c
10
3
7
5
4
15
2
5
14
1
6
OAc
OAc
O
OAc
Br
OAc
OAc
f
g
c
d
e
O
O
10
8
9
7
OH
OH
OH
OH
O
OH
h
g
i
OH
OH
O
O
11
a. LiAlH , Et O, 2 h, 94.5%; b. Ac O, Py, 2 h, 20ꢄC, 98%; c. Ph P, I , CH Cl , 2 h, 20ꢄC, 98%; d. Na CrO , AcONa, Ac O, AcOH, C H ,
12
3
4
2
2
3
2
2
2
2
4
2
6 6
60ꢄC, 2 h, 60%; e. NBS, CCl , 2 h, ꢅ, 80%; f. AcOK, DMFA, 22ꢄC, 2 h, 80%; g. 1% K CO , MeOH, 1 h, 22ꢄC, 76%; h. H O , NaOH, MeOH,
4
2
3
2 2
22ꢄC, 5 h, 76%; i. NH NH ·H O, 2.5 h, 87%
2
2
2
Scheme 1
The oxidizing reagent should attack 11 from the ꢀ-side because its ꢁ-side is sterically strongly shielded. This followed
from a literature search for compounds that were structurally similar to 11 [14, 15]. Epoxidation of unsaturated diol 13 upon
oxidation by metachloroperbenzoic acid to form epoxydiol 14 (85% yield) also occurred stereospecifically [16].
OH
OH
O
OH
OH
O
O
13
14
NMR spectral data indicated that the epoxide group in 12 had the ꢀ-orientation. The degree of deshielding of the
C-10 methyl in 12 was similar to that for epoxydiol 14.
Reaction of 12 with hydrazine hydrate (Wharton–Bolen reaction) formed 11-homodrim-7-en-9ꢀ,12,13-triol (3) in
high yield (87%). Its structure was confirmed by spectral data (see Experimental). Its overall yield calculated from
norambreinolide (4) was 14.3%. The product yields were high in most steps. The used reagents were available and inexpensive.
EXPERIMENTAL
Melting points were determined on a Boetius heating stage. IR spectra were recorded on a Specord 74
13
spectrophotometer. PMR and C NMR spectra were taken from CDCl solutions (2–3%) on a Bruker Avance DRX 400
3
spectrometer (400.13 and 100.61 MHz) with TMS internal standard. Chemical shifts are given on the ꢂ scale in ppm relative
to CHCl resonances as an internal standard (resonances at 7.24 and 77.00 ppm, respectively). Spin–spin coupling constants
3
13
are given in Hz. Resonances in C NMR spectra were assigned using DEPT, COSY, HMQC, and HMBC programs and by
comparison with spectra of related compounds [6, 16]. High-resolution mass spectral analysis was performed on an AEI MS
902 spectrometer (EI, 70 eV). Reaction mixtures were worked up by extracting with ether, washing the extract with H O until
2
neutral, drying over Na SO , filtering, and vacuum distilling solvent. The course of reactions was monitored by TLC on
2
4
Sorbfil plates with detection by Ce(SO ) solution (1%) in aqueous H SO (2 N) with subsequent heating at 80°C for 5 min.
4 2
2
4
Column chromatography used Acros silica gel (60/200 ꢃm). Columns were eluted by a gradient of petroleum ether:EtOAc
mixtures of increasing polarity. Solvents were dried and distilled before use.
575

Reduction of Norambreinolide (4). A solution of 4 (10 g, 0.04 mol) in anhydrous Et O (400 mL) was treated in
2
portions over 10 min with LiAlH (4.72 g, 0.12 mol) and stirred for 2 h at 22°C (TLC monitoring). The usual work up of the
4
solid afforded by recrystallization from ether crystalline diol 5 (10.28 g, 94.5%), mp 129.5–131°C (lit. [7] mp 131–132°C).
–1
IR spectrum (KBr, ꢆ, cm ): 1054, 3423.
PMR spectrum (400 MHz, CDCl , ꢂ, ppm, J/Hz): 0.79 (6H, s, CH -14, CH -15), 0.87 (3H, s, CH -16), 0.89–1.18 and
3
3
3
3
1.25–1.68 (14H, both m), 1.87–1.92 (2H, m, H-1), 3.74–3.78 (1H, m, H-9), 3.40–3.46 (1H, m, H-6), 4.20 (1H, br.s, OH).
13
C NMR spectrum (100.61 MHz, CDCl , ꢂ, ppm): 15.33 (C-14), 18.41 (C-16), 20.43 (C-2), 21.48 (C-15), 24.55
3
(C-7), 27.83 (C-12), 33.26 (C-13), 33.42 (C-4), 38.95 (C-10), 39.34 (C-3), 41.89 (C-1), 44.10 (C-6), 56.02 (C-9), 59.32 (C-5),
63.90 (C-11), 72.86 (C-8).
Acetylation of 11-Homodriman-8ꢀ,12-diol (5). A solution of diol 5 (10.28 g, 0.04 mol) in Py (51 mL) was treated
with freshly distilledAc O (25.6 mL, 0.27 mol), held for 2 h at 22°C (TLC monitoring), stirred, treated with cold H SO (10%,
2
2
4
50 mL), and extracted with ether (3 ꢇ 50 mL). The combined ether extract was washed with H SO (10%, 30 mL), H O
2
4
2
(30 mL), saturated NaHCO solution (2 ꢇ 30 mL), and H O (2 ꢇ 30 mL); dried; and filtered. The solvent was distilled off. The
3
2
liquid residue (12 g) was chromatographed over a column of SiO (360 g) with elution by petroleum ether:EtOAc (8:2) to
2
afford liquid 12-acetoxy-11-homodrim-13-ol (6, 11.63 g, 98%).
Spectral data of 6 were identical to those published [8–10]. Compound 6 was conclusively identified by comparison
–1
with an authentic sample that was obtained by us earlier [8]. IR spectrum (KBr, ꢆ, cm ): 1032, 3468 (OH); 1245, 1737 (OAc).
PMR spectrum (400 MHz, CDCl , ꢂ, ppm, J/Hz): 0.79 (6H, s, CH -14, 15), 0.87 (3H, s, CH -16), 0.92 (1H, dd,
3
3
3
J = 0.5, 12, H-5), 1.07–1.81 (2H, m, H-11), 1.16 (3H, s, CH -13), 1.90 (1H, d, J = 4, 16, H-9), 2.05 (3H, s, COCH ), 4.13 (2H,
3
3
m, H-12).
13
C NMR spectrum (100.61 MHz, CDCl , ꢂ, ppm): 15.31 (C-16), 18.40 (C-2), 20.48 (C-6), 21.13 (COCH ), 21.47
3
3
(C-15), 23.94 (C-13), 24.47 (C-11), 33.27 (C-4), 33.38 (C-14), 38.75 (C-10), 39.60 (C-1), 41.88 (C-3), 44.39 (C-7), 56.07
(C-5), 58.03 (C-9), 66.62 (C-12), 73.56 (C-8), 171.17 (COCH ).
3
Dehydration of 12-Acetoxy-11-homodriman-8ꢀ-ol (6). Monoacetate 6 was dehydrated according to the literature
method [11]. A solution of triphenylphosphine (12.3 g, 0.04 mol) in CH Cl (202 mL) was stirred at room temperature, treated
2
2
with iodine (5.9 g, 0.046 mol), stirred for another 10 min, treated with a solution of 6 (11.69 g, 0.039 mol) in CH Cl (118 mL),
2
2
stirred at the same temperature for another 2 h (TLC monitoring), treated with Na SO solution (5%, 250 mL), stirred for 10
2
3
min, and extracted with CH Cl (2 ꢇ 50 mL). The extract was washed with H O (2 ꢇ 100 mL) and saturated NaCl solution
2
2
2
(2 ꢇ 100 mL), dried over anhydrous Na SO , and filtered. The solvent was vacuum distilled. The residue (20 g) was
2
4
chromatographed over a column of SiO (320 g) with elution by petroleum ether to afford a liquid mixture of isomeric
2
–1
unsaturated acetates 7 (10.68 g, 98%). IR spectrum (film, ꢆ, cm ): 1231, 1740 (OAc).
PMR spectrum (400 MHz, CDCl , ꢂ, ppm): 0.83 (3H, s, CH -14), 0.88 (3H, s, CH -15), 0.94 (3H, s, CH -16), 1.62
3
3
3
3
(3H, s, CH -13), 2.01 (3H, s, OAc), 3.97–4.03 (2H, m, H-12).
3
The contents of the isomers with the tri-substituted (19%) and exocyclic (17%) double bonds were determined from
the ratio to the total resonance intensity of C(12)H groups. The content of the isomer with the tetra-substituted double bond
2
(64%) [singlet C(13)H at 1.62 ppm] was determined by difference.
3
Oxidation of the Mixture of Unsaturated Acetates 7 by Sodium Chromate. The mixture of acetates 7 was oxidized
by sodium chromate by the literature method [13]. A solution of the mixture of unsaturated acetates 7 (10.68 g, 0.038 mol) in
anhydrous benzene (550 mL) was treated with glacial AcOH (159.5 mL, 2.81 mol) and freshly distilled Ac O (159.5 mL,
2
1.69 mol), treated with NaOAc (19.06 g, 0.288 mol) and Na CrO (34 g, 0.158 mol), and stirred for 2 h at 60°C. A part of the
2
4
benzene (185 mL) was vacuum distilled. The mixture was cooled to 22°C, treated with H O (300 mL), and extracted with
2
ether (3 ꢇ 50 mL). The extract was washed with NaHCO solution (5%, 50 mL) and H O (2 ꢇ 50 mL), dried over anhydrous
3
2
Na SO , and filtered. The ether was vacuum distilled. The residue (10.7 g) was chromatographed over a column of SiO
2
4
2
(320 g) with elution by petroleum ether:EtOAc (96:4) to afford crystalline 12-acetoxy-11-homodrim-8(9)-en-7-one (8, 6.73 g,
–1
60%), mp 59–60°C (petroleum ether). IR spectrum (KBr, ꢆ, cm ): 1232, 1745 (OAc), 1600 (conjugated C=C), 1656 (conjugated
C=O).
PMR spectrum (400 MHz, CDCl , ꢂ, ppm, J/Hz): 0.89 (3H, s, CH -14), 0.92 (3H, s, CH -15), 1.09 (3H, s, CH -16),
3
3
3
3
1.81 (3H, s, CH -13), 2.07 (3H, s, OAc), 4.13 (2H, m, H-12).
3
13
C NMR spectrum (100.61 MHz, CDCl , ꢂ, ppm): 11.78 (C-13), 18.04 (C-16), 18.57 (C-2), 20.96 (C-15), 21.30
3
(COCH ), 28.71 (C-11), 32.50 (C-14), 33.13 (C-4), 35.23 (C-6), 36.01 (C-1), 40.65 (C-10), 41.21 (C-3), 50.10 (C-5), 62.37
3
(C-12), 132.10 (C-8), 162.45 (C-9), 170.85 (COCH ), 200.05 (C-7).
3
576

Bromination of Ketoacetate 8 by NBS. A solution of ketoacetate 8 (6.73 g, 0.023 mol) in anhydrous CCl
4
(132.5 mL) was treated with freshly recrystallized NBS (4.15 g, 0.023 mol). The resulting mixture was refluxed for 2 h,
cooled, and filtered. The solvent was vacuum distilled. The residue (8.89 g) was chromatographed over a column of SiO
2
(178 g) with elution by petroleum ether:EtOAc (99:1) to afford crystalline 12-acetoxy-13-bromo-11-homodrim-8(9)-en-7-one
–1
(9, 6.84 g, 80%), mp 63–64°C (petroleum ether). IR spectrum (KBr, ꢆ, cm ): 595, 1129 (Br), 1224, 1743 (OAc), 1600
(conjugated C=C), 1671 (conjugated C=O).
PMR spectrum (400 MHz, CDCl , ꢂ, ppm, J/Hz): 0.90 (3H, s, CH -15), 0.93 (3H, s, CH -14), 1.11 (3H, s, CH -16),
3
3
3
3
1.00–2.40 (11H, m), 4.22 (1H, d, J = 9.6, H-13) and 4.36 (1H, d, J = 9.6, H-13), 4.25 (2H, m, H-12).
13
C NMR spectrum (100.61 MHz, CDCl , ꢂ, ppm): 17.89 (C-2), 18.43 (C-16), 20.93 (C-15), 21.37 (COCH ), 24.36
3
3
(C-13), 28.67 (C-11), 32.43 (C-14), 33.27 (C-4), 35.20 (C-6), 35.57 (C-1), 41.04 (C-3), 41.17 (C-10), 49.52 (C-5), 62.21
(C-12), 133.66 (C-8), 167.23 (C-9), 170.84 (COCH ), 197.17 (C-7).
3
Preparation of 12,13-Diacetoxy-11-homodrim-8-en-7-one (10). A solution of 9 (6.84 g, 0.018 mol) in DMF
(290 mL) was treated with KOAc (4.1 g, 0.05 mol), stirred for 2 h at 22°C (TLC monitoring), treated with H O (300 mL), and
2
extracted with ether (3 ꢇ 100 mL). The extract was washed with H O (2 ꢇ 100 mL), dried over anhydrous Na SO , and
2
2
4
filtered. The solvent was vacuum distilled. The residue (5.56 g) was chromatographed over a column of SiO (120 g) with
2
elution by petroleum ether:EtOAc (95:5) to afford crystalline 12,13-diacetoxy-11-homodrim-8-en-7-one (10, 5.16 g, 80%),
–1
mp 78–79°C (petroleum ether). IR spectrum (KBr, ꢆ, cm ): 1251, 1740 (OAc), 1600 (conjugated C=C), 1665 (conjugated
C=O).
PMR spectrum (400 MHz, CDCl , ꢂ, ppm, J/Hz): 0.90 (3H, s, CH -15), 0.93 (3H, s, CH -14), 1.13 (3H, s, CH -16),
3
3
3
3
2.03 (3H, s, OAc), 2.05 (3H, s, OAc), 1.0–2.20 (9H, m), 4.05–4.25 (2H, m, H-12), 4.77 (1H, d, J = 11.6) and 4.90 (1H, d,
J = 11.6) (AB-system, H-13).
13
C NMR spectrum (100.61 MHz, CDCl , ꢂ, ppm): 18.39 (C-16), 18.45 (C-2), 20.85 (OAc), 20.99 (OAc), 21.35
3
(C-15), 28.39 (C-1), 32.43 (C-14), 33.29 (C-4), 35.22 (C-6), 35.67 (C-11), 41.03 (C-3), 41.08 (C-10), 49.66 (C-5), 57.90
(C-13), 63.08 (C-12), 131.20 (C-8), 169.22 (C-9), 169.63 (OAc), 170.37 (OAc), 196.40 (C-7).
Saponification of 10. A solution of ketodiacetate 10 (5.16 g, 0.014 mol) in MeOH (90 mL) was treated with K CO
2
3
solution (1%) in MeOH (206 mL). The mixture was held at ambient temperature under an argon atmosphere for 1 h (TLC
monitoring), treated with H O (300 mL), and extracted with ether (3 ꢇ 50 mL). The ether extract was washed with H SO
2
2
4
solution (10%, 100 mL) and H O (2 ꢇ 50 mL), dried over anhydrous Na SO , and filtered. The solvent was vacuum distilled
2
2
4
to afford crystalline 11-homodrim-8(9)-en-12,13-diol-7-one (11, 2.97 g, 76%), mp 109–110°C (Et O). IR spectrum (KBr, ꢆ,
2
–1
cm ): 1047, 3282, 3306 (OH), 1650 (conjugated C=C), 1660 (conjugated C=O).
PMR spectrum (400 MHz, CDCl , ꢂ, ppm, J/Hz): 0.99 (3H, s, CH -15), 0.93 (3H, s, CH -14), 1.14 (3H, s, CH -16),
3
3
3
3
1.15–2.00 (3H, m), 2.30–2.80 (4H, m), 3.70–3.90 (2H, m, H-12), 4.30 (1H, d, J = 12) and 4.40 (1H, d, J = 12) (AB-system,
H-13).
13
C NMR spectrum (100.61 MHz, CDCl , ꢂ, ppm): 18.40 (C-16), 18.50 (C-2), 21.37 (C-15), 31.89 (C-1), 32.43
3
(C-14), 33.29 (C-4), 35.33 (C-6), 35.78 (C-11), 40.89 (C-10), 41.07 (C-3), 49.82 (C-5), 56.89 (C-13), 61.32 (C-12), 134.65
(C-8), 168.33 (C-9), 201.06 (C-7). Mass spectrum (EI, 70 eV, m/z, I , %): 266.17743.
rel
Epoxidation of 11. A solution of 11 (2.97 g, 0.01 mol) in MeOH (46.5 mL) was treated with NaOH solution (6 N) in
MeOH (26.7 mL), stirred at ambient temperature for 15 min, cooled to 0°C, treated with H O solution (26.7 mL, 35%), stirred
2
2
at room temperature for 5 h (TLC monitoring), treated with H O (350 mL), and extracted with ether (3 ꢇ 100 mL). The extract
2
was washed with saturated NaCl solution (100 mL), dried over anhydrous Na SO , and filtered. The solvent was vacuum
2
4
distilled to afford crystalline 8,9ꢀ-epoxy-11-homodriman-12,13-diol-7-one (12, 2.38 g, 76%), mp 104–105°C (Et O).
2
–1
IR spectrum (KBr, ꢆ, cm ): 1042 (epoxy group), 1053, 3342 (OH), 1702 (C=O).
PMR spectrum (400 MHz, CDCl , ꢂ, ppm, J/Hz): 0.85 (3H, s, CH -14), 0.86 (3H, s, CH -15), 0.96 (3H, s, CH -16),
3
3
3
3
1.00–1.90 (9H, m), 2.00–2.30 (3H, m), 2.48 (1H, dd, J = 7.2, 19.2, H -6), 3.73-3.90 (2H, m, H-12), 3.70 (1H, d, J = 12.4) and
ꢁ
4.18 (1H, d, J = 12.4) (AB-system, H-13).
13
C NMR spectrum (100.61 MHz, CDCl , ꢂ, ppm): 16.79 (C-16), 18.42 (C-2), 20.68 (C-14), 28.46 (C-11), 32.46
3
(C-15), 33.33 (C-4), 34.57 (C-1), 36.06 (C-6), 38.83 (C-10), 41.08 (C-3), 41.59 (C-5), 59.69 (C-12), 60.29 (C-13), 66.47
(C-8), 74.00 (C-9), 210.87 (C-7).
Wharton–Bolen Rearrangement of 12. A mixture consisting of epoxide 12 (1 g, 3.73 mmol) and hydrazine hydrate
(15 mL) was stirred at room temperature for 2.5 h under an Ar atmosphere (TLC monitoring), treated with H O (30 mL), and
2
extracted with ether (3 ꢇ 20 mL). The extract was washed with saturated NaCl solution (50 mL), dried over anhydrous
577

Na SO , and filtered. The solvent was vacuum distilled to afford crystalline triol 3 (0.82 g, 87%), mp 106–107°C (Et O).
2
4
2
–1
IR spectrum (KBr, ꢆ, cm ): 1037, 1153, 3310 (OH), 818, 1693 (C=C).
PMR spectrum (400 MHz, CDCl , ꢂ, ppm): 0.82 (6H, s, CH -14, 15), 1.20 (3H, s, CH -16), 3.45–3.50 (6H, dd, H-11,
3
3
3
12, 13), 5.88–5.89 (1H, d, H-7).
13
C NMR spectrum (100.61 MHz, CDCl , ꢂ, ppm): 15.66 (C-16), 18.43 (C-2), 22.18 (C-14), 29.71 (C-11), 30.72
3
(C-6), 32.90 (C-4), 33.38 (C-15), 33.48 (C-1), 41.70 (C-3), 41.78 (C-10), 41.94 (C-5), 60.76 (C-12), 65.93 (C-13), 77.89
(C-9), 130.92 (C-7), 139.10 (C-8).
ACKNOWLEDGMENT
The authors from P. Poni Institute of the Romanian Academy of Sciences are thankful for support of Project No.
264115 (STREAM) that is a component of European Project FP7-REGPOT-2010-1. One of us (K.E.) thanks the World
Federation of Scientists (WFS, Switzerland) for support in carrying out the individual project “Elaboration of Efficient Method
for the Synthesis of 11-Homowarburganal from Norambreinolide.”
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