Two approaches to the synthesis of 9-oxo-and 10-hydroxy-2E-decenoic acids, important components of queen substance and royal jelly of honeybees Apis mellifera

Article abstract of DOI:10.1007/s10600-008-0019-7

Two approaches to the synthesis of 9-oxo-and 10-hydroxy-2E-decenoic acids, biologically active components of queen substance and royal jelly of honeybees, respectively, were proposed starting with allyl bromide and 1,7-octadiene and using chemo-and regioselective transformations of the common intermediate building block 7-octen-1-ylacetate.

Full text of DOI:10.1007/s10600-008-0019-7

Chemistry of Natural Compounds, Vol. 44, No. 1, 2008
TWO APPROACHES TO THE SYNTHESIS OF 9-OXO- AND
10-HYDROXY-2E-DECENOIC ACIDS, IMPORTANT
COMPONENTS OF QUEEN SUBSTANCE AND
ROYAL JELLY OF HONEYBEES Apis mellifera
1
1
3
G. Yu. Ishmuratov, M. P. Yakovleva, K. A. Tambovtsev,
UDC 547.315+547.323+
547.391.8
1
1
1
Yu. V. Legostaeva, L. V. Kravchenko, N. M. Ishmuratova,
2
and G. A. Tolstikov
Twoapproachestothe synthesisof 9-oxo-and10-hydroxy-2E-decenoicacids, biologicallyactivecomponents
of queen substance and royal jelly of honeybees, respectively, were proposed starting with allyl bromide and
1
,7-octadiene and using chemo- and regioselective transformations of the common intermediate building
block 7-octen-1-ylacetate.
Key words: allylbromide, 1,7-octadiene, 7-octen-1-ylacetate,7-oxooct-1-ylacetate, 8-hydroxyoct-1-ylacetate, 9-oxo-2E-
decenoic acid, 10-hydroxy-2E-decenoic acid, synthesis.
9
-Oxo- (1) and 10-hydroxy-2E-decenoic (2) acids have been identified as the most important components of queen
substance and royal jelly, respectively, of the honeybee Apis mellifera L.
Oxoacid 1isa polyfunctional pheromone ofhoneybees, plays the exclusive role ofregulating their behavior and activity
[
1], and possesses significant pharmacological properties (antibacterial, anti-inflammatory, accelerator of graft wound and
thermal burn healing, immunomodulator) [2] and antidote activity[3]. Compound 2 has bactericidal, fungicidal, and antitumor
properties [4].
MgBr(CH ) OTHP
2
5
Br
OTHP
CuI - 2,2'-PyPy
(CH2)4
4
3
a. iBu AlH, ZrCl
b. O2
2
4
AcCl, AcOH
c. H2SO4 - H2O
Ac O, Py
2
OAc
OH
6
5
O , PdCl - Cu Cl
2
2
2
2
d. 9-BBN
e. H O , AcONa
2
2
O
HO
OAc
OAc
7
8
[5]
PCC, CH Cl
2
2
O
[14]
O
CO H
HO
CO2H
2
OAc
1
9
2
1
) Institute of Organic Chemistry, Ufa Scientific Center, Russian Academy of Sciences, RF, 450054, Ufa, prosp.
Oktyabrya, 71, fax (3472) 35 60 66, e-mail: insect@anrb.ru; 2) N. N. Vorozhtsov Novosibirsk Institute of Oragnic Chemistry,
Siberian Division, Russian Academy of Sciences, 630090, Novosibirsk, posp. Akad. Lavrent′eva, 9; 3) Birsk State Social-
Pedagogical Academy, RF, Republic of Bashkortostan, 452320, Birsk, ul. Internatsional′naya, 10. Translated from Khimiya
Prirodnykh Soedinenii, No. 1, pp. 58-60, January-February, 2008. Original article submitted October 24, 2007.
©
0
009-3130/08/4401-0074 2008 Springer Science+Business Media, Inc.
7
4

Several syntheses of 1 and 2 have been reported. They differ in the methods of introducing oxo-, hydroxy-, and
α,β-unsaturated carboxylic acid groups [5].
We propose two approaches to preparing acids 1 and 2 that are based on previously described transformations [6, 7]
of keto-7- and aldehydo-9-acetates using the Doebner reaction for constructing the conjugated carboxylic acid. Intermediates
7
7
and 9, in turn, were synthesized from available allyl bromide and 1,7-octadiene (3) [8] using their common key synthon
-octen-1-ylacetate (6). For this, the former of these was first converted by a catalyzed (CuI:2,2′-bipyridyl) cross-conjugation
reaction into the tetrahydropyran ether of 7-octen-1-ol (4) and then into the required acetate (6). The other approach was based
on selective monohydroalumination of 3 by diisobutylaluminum hydride at room temperature in the presence of ZrCl catalyst
4
(
in contrast with the previouslyreported [8] thermal version using triisobutylaluminum at 100°C) and oxidation ofthe resulting
organaluminum compound to 7-octen-1-ol (5), which was then converted to acetate 6 as usual.
Further transformations of 6 in the direction of 1 consisted of its one-step Walker—Tsuji transformation into
ketoacetate 7. The building block of 9 was constructed for hydroxyacid 2 through a two-step synthesis using the intermediate
monoester of 1,8-octanediol 8 based on chemo- and regioselective hydroboration—oxidation reactions.
EXPERIMENTAL
IR spectra were recorded on a UR-20 instrument as thin layers. PMR spectra in CDCl were recorded on a Tesla
3
BS-567 spectrometer (operating frequency 100 MHz) with TMS internal standard. GC was performed on Chrom-5 [column
length 1.2 m, stationary phase silicone SE-30 (5%) on Chromaton N-AW-DMCS (0.16-0.20 mm), operating temperature 50-
3
00°C] and Chrom-41 [column length 2.4 m, stationary phase PEG-6000, operating temperature 50-200°C] instruments with
He carrier gas. Column chromatographyused SiO (70-230, Lancaster, England). TLCmonitoringused SiO (Sorbfil, Russia).
2
2
Elemental analyses of all compounds agreed with those calculated.
1
-(2-Tetrahydropyranyloxy)-7-octene (4). A suspension of CuI (2.85 g, 15.0 mmol) in absolute THF (58 mL) was
treated with 2,2′-bipyridine (2.34 g, 15.0 mmol), stirred for 0.5 h (20°C, Ar), cooled to 2°C, treated with allylbromide
10.41 g, 86.0 mmol) in absolute THF (17 mL), stirred for 10 min, treated with Grignard reagent prepared from Mg (1.11 g,
6.0 mg-at) and 1-(2-tetrahydropyranyloxy)-5-bromopentane (2) as before [9] in THF (40.5 mL), stirred for 1 h at 10°C, and
treated with Et O (500 mL). The organic layer was separated, washed with saturated NaCl solution, dried over Na SO , and
(
4
2
2
4
−
1
evaporated. The residue was chromatographed (SiO , hexane:Et O, 15:1) to afford 4 (5.82 g, 69%). IR spectrum (ν, cm ):
2
2
3
080, 1650, 920 (CH=CH ), 1150, 1090, 1045 (C–O–C).
2
7
-Octen-1-ol (5). A solution of 1,7-octadiene (3, 5.00 g, 45.5 mmol) prepared as before [8] in absolute hexane (45 mL)
was stirred (20°C, Ar), treated with ZrCl (0.29 g, 1.25 mmol) and diisobutylaluminum hydride (73% solution, 11.5 mL,
4
4
3
5.9 mmol) in toluene, stirred for 7 h at 20°C, purged successively with dry air (0-20°C, 1 h) and oxygen (20°C, 1 h, 30-40°C,
h), cooled to 0°C, treated dropwise with H SO (38 mL, 10%), stirred for 1 h at room temperature, and extracted with
2
4
Et O (3 × 100 mL). The combined extracts were washed successivelywith saturated solutions of NaHCO and NaCl, dried over
2
3
−
1
Na SO , evaporated, and distilled to afford 5 (4.30 g, 74%), bp 64-66°C (7 mm). IR spectrum (ν, cm ): 3550 (OH), 3090,
2
4
1
640, 920 (CH=CH ). PMR spectrum (δ, ppm): 1.20-1.70 (8H, m, H-2—H-5), 2.15-2.30 (2H, m, H-6), 3.66 (2H, t, J = 7 Hz,
2
H-1), 5.0-5.4 (2H, m, H-8), 5.6-5.9 (1H, m, H-7), similar to the literature data [10].
-Octen-1-ylacetate (6), a: ether 4 (5.75 g, 27.1 mmol) was treated with a mixture of AcOH and AcCl (10:1, 27 mL),
stored for 48 h at 30-40°C, diluted with Et O (250 mL), washed successively with saturated solutions of NaHCO and NaCl,
7
2
3
−
1
dried over MgSO , and evaporated to afford 6 (3.41 g, 74%). IR spectrum (ν, cm ): 3090, 1645, 920 (CH=CH ), 1745, 1250
4
2
(
OAc). PMR spectrum (δ, ppm): 1.30-1.75 (8H, m, H-2—H-5), 2.05 (3H, s, CH CO), 2.15-2.30 (2H, m, H-6), 4.06 (2H, t,
3
J = 6.5 Hz, H-1), 5.00-5.40 (2H, m, H-8), 5.60-5.90 (1H, m, H-7).
b: a mixture of 5 (4.00 g, 31.3 mmol), dryPy(63.7 mL), and Ac O (27.3 mL) was stored for 24 h at room temperature
2
and evaporated. The residue was dissolved in Et O (250 mL), washed with HCl (10%) and saturated solutions of NaHCO and
2
3
NaCl, dried over MgSO , and evaporated. The residue was chromatographed (SiO , hexane:Et O, 9:1) to afford 6 (4.30 g,
4
2
2
8
1%), spectral properties identical to those for the compound in a.
7
-Oxooct-1-ylacetate (7). A mixture of PdCl (0.38 g, 2.1 mmol), Cu Cl (2.19 g, 11.0 mmol), DMF (11.4 mL), and
2 2 2
H O (1.4 mL) was stirred for 1 h under O , treated with 6 (3.40 g, 20.0 mmol), stirred for 6 h to absorb O (270 mL), diluted
2
2
2
75

with CHCl (250 mL), washed successively with HCl (5%) and saturated NaCl solution, dried over Na SO , and evaporated
3
2
4
to afford 7 (2.42 g, 65%). The IR and PMR spectra were identical to those reported earlier [11, 12].
8
-Hydroxyoct-1-ylacetate (8). A suspension of 9-BBN (3.55 g, 29.1 mmol) in absolute THF (36 mL) at 10°C was
treated with a solution of 7 (3.50 g, 20.6 mmol) in absolute THF (12 mL), stored for 2 h, cooled to 0°C, treated with a solution
of NaOAc (5.92 g, 72.2 mmol) in H O (14 mL) and dropwise with H O (30%, 21.3 mL), stirred for 2 h at room temperature,
2
2 2
diluted with Et O (300 mL), washed successivelywith saturated NaCl solution, Na S O solution (0.1 N), again with saturated
2
2 2 3
NaCl solution, dried over Na SO , and evaporated. The residue was chromatographed (SiO , hexane:ether, 10:1) to afford 8
2
4
2
(2.75 g, 71%). The IR and PMR spectra were identical to those reported earlier [13].
8
-Acetoxyoctanal (9). A suspension of PCC (5.32 g, 24.7 mmol) in dry CH Cl (28 mL, Ar, 20°C) was treated in one
2
2
portion with a solution of 8 (2.70 g, 14.4 mmol) in dry CH Cl (3 mL), diluted after 1.5 h with Et O (35 mL), and filtered
2
2
2
through a layer of SiO (15 cm). The solid was washed with Et O. The combined filtrate was evaporated to afford 9 (2.38 g,
2
2
8
9%). The IR and PMR spectra were identical to those reported earlier [7].
0-Hydroxy-2E-decenoic acid (2) was prepared from 9 in two steps in overall yield 49% as before [14], mp 64-65°C
15]. The IR and PMR spectra were identical to those reported earlier [14].
-Oxo-2E-decenoic acid (1) was prepared from 7-oxooct-1-ylacetate (7) in three steps in overall yield 34% as before
15], mp 52-54°C [16]. The IR and PMR spectra were identical to those reported earlier [17].
1
[
[
9
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6