Selective protection of hydroxyls in natural type E and F prostaglandins

Article abstract of DOI:10.1007/s10600-012-0224-2

Methods for selective protection of hydroxyls in natural type E and F prostaglandins were developed.

Full text of DOI:10.1007/s10600-012-0224-2

Chemistry of Natural Compounds, Vol. 48, No. 2, May, 2012 [Russian original No. 2, March-April, 2012]
SELECTIVE PROTECTION OF HYDROXYLS IN NATURAL
TYPE E AND F PROSTAGLANDINS
1*
2
V. V. Bezuglov and I. V. Serkov
UDC 547.514.48
Methods for selective protection of hydroxyls in natural type E and F prostaglandins were developed.
Keywords: prostaglandins, protecting groups.
Prostaglandins are polyfunctional compounds that characteristically exhibit broad spectra of physiological activity,
e.g., a combination of dilatory (on smooth muscle of bronchi), constrictive (on smooth muscle of the gastro-intestinal tract),
pro- or antiaggregation (on platelets), and hypo- or hypertensive activities [1]. Such a broad spectrum of biological activity
prevents the broad application of natural prostaglandins as drugs because of the many side effects. Modification of natural
prostaglandins in order to alter their spectra of biological activity, decrease the types of activity responsible for the appearance
of undesired side effects, and increase simultaneously the desired types of biological activity would enable these limitations to
be obviated [2]. Modification of natural prostaglandins recently became critical again because of the discovery of new natural
prostanoids, prostamides (ethanolamides) and 2-glycerol esters, cyclo-oxygenase derivatives of the endocannabinoids
anandamide and 2-arachidonylglycerol [3].
One direction of such modification is the change of a functionally significant prostaglandin structural element, in
particular, a hydroxyl. The chemical properties of prostaglandin hydroxyls differ little. Regioselective modification of one of
the hydroxyls, for example, adding a fluoride or acyl group, is usually not possible. However, the differences are adequate for
selective protection of the hydroxyls that must be retained intact in the target compound. Modification of natural type E and
F prostaglandins with two and three free hydroxyls, respectively, cause the greatest challenges for selective protection.
Protecting group strategies that are compatible with the prostaglandin chemical properties should be used to solve the
problem of differentiating the hydroxyls. Thus, acetyls must be removed in basic solution. This is not compatible with type E
prostaglandins whereas type F prostaglandins are stable under such conditions. Herein we describe the application of silyl and
acetyl protecting groups for differentiating the hydroxyls. The resulting synthons with a single free hydroxyl could be converted
into fluorodeoxyprostaglandins with unique biological properties through the action of reagents based on aminosulfurtrifluorides
[4, 5].
Selective protection of hydroxyls can be effected either by selective addition of a blocking group or its selective
removal. Acombination of various protecting groups is possible where prostaglandin is converted in the first step into a partial
silyl ether whereas the free hydroxyls are acetylated. Reagents that are sensitive to the steric environment of the hydroxyls
must be used for such conversions. Thus, the C-9 hydroxyl of the methyl ether C atom of prostaglandin F , which is located
2ꢀ
in the cis-position to C-8 of the prostaglandin side chain, is not silylated even with a 100-fold excess of reagent if
trimethylsilyldiethylamine is used for the silylation. The 11,15-disilyl derivative is formed exclusively [6].
We found that a mixture of monosilyl ethers at the 11- or 15-hydroxyls was formed with a slight excess of silylating
reagent (less than 10-15-fold). These gave a mixture of diacetates 2a and 2b in a 7:1 ratio (Scheme 1) after acetylation by
acetic anhydride in the presence of Py and removal of the TMS protection. The ratio of these acetates was reversed if the
limited deacetylation of known triacetate 3 [7] was carried out using K CO in MeOH. In this instance, diacetate 2b made up
2
3
65% of the total diacetate fraction that was formed in 75% yield taking into account unreacted triacetate 3. These diacetates
could be converted into the corresponding methyl ethers of fluorodeoxyprostaglandins 4 and 5 by the action of MSTF and
1) M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences,
117997, GSP, Moscow, fax: 7 (095) 335 71 03, e-mail: vvbez@oxylipin.ibch.ru; 2) Institute of Physiologically Active
Compounds, RussianAcademy of Sciences, 142432, Moscow Oblast, Chernogolovka, Severnyi Pr., 1. Translated from Khimiya
Prirodnykh Soedinenii, No. 2, March–April, 2012, pp. 260–265. Original article submitted August 22, 2011.
©
0009-3130/12/4802-0291 2012 Springer Science+Business Media, Inc.
291

removal of the protective acetates. Then, fluorodeoxyprostaglandins could be obtained from them as the free acids, e.g.,
15-fluoro-15-deoxyprostaglandin F (6) [4]; from prostanoid 4, the methyl ether of 5-iodo-15-fluoro-15-deoxyprostaglandin
2ꢀ
I (7) by iodine cyclization and then 15-fluoro-15-deoxyprostacyclin [8].
1
AcO
HO
6
CO Me
ii
2
CO Me
2
9
5
14
15
20
11
13
OAc
AcO
OH
HO
AcO
1
3
i - iii
iv
AcO
CO Me
CO Me
2
2
+
HO
OH
OAc
AcO
HO
2a
2b
v, vi
v, vi
HO
F
CO Me
2
CO Me
2
OH
HO
4
5
F
I
vii
viii
HO
O
CO Me
2
CO H
2
HO
HO
F
6
F
7
i. TMSNEt , acetone, –40°C, 1 h; ii. Ac O, Py, benzene, 23°C, 18 h; iii. 70% AcOH, 30°C, 2 h; iv. K CO ,
2
2
2
3
MeOH, 23°C, 30 min; v. MSTF, CH Cl , –78°C, 1 h; vi. MeOH, MeONa, 40°C, 2 h; vii. I , aq. NaHCO ,
2
2
2
3
Et O, 4°C, 18 h; viii. 40% KOH, MeOH–dioxane, 35°C, 3h
2
Scheme 1
The tert-butyldimethylsilyl (BDMS) group (Scheme 2) can also be used as a temporary protective group for
differentiating the hydroxyls in type F prostaglandins. Limited desilylation of the tri-BDMS derivative of prostaglandin F
2ꢀ
(8) by HF (50%) gave a mixture of di-BDMS ethers 9 and 10, the ratio of which depended on the reaction time. However,
prostanoid 9 dominated in all instances. Then, both silyl ethers 9 and 10 could be converted into the corresponding 15- and
11-fluoro derivatives. Difficultly accessible prostaglandin D (11) could be synthesized from 10.
2
BDMSO
HO
CO Me
CO Me
2
9
2
i
HO
BDMSO
OH
OBDMS
1
8
ii
BDMSO
RO
HO
O
CO Me
iii, iv
for 10
2
CO H
2
11
15
OR
1
OH
9, 10
11
9: R = t-BuMe Si, R = H
2
1
10: R = H, R = t-BuMe Si
1
2
i. DMF, BDMSCl, imidazole, 25ꢁC, 18 h; ii. 50% HF, 25ꢁC, 5 min; iii. CrO , acetone, 4ꢁC, 2 min; iv. THF, 50% HF, 25ꢁC, 4 h
3
Scheme 2
292

As noted above, the 9-OH of prostaglandin F was less reactive in the aforementioned blocking–deblocking reactions
2ꢀ
because of steric hindrance. This allowed the corresponding C-9 monosilyl or monoacetyl derivatives of prostaglandin F
2ꢀ
and also protected derivatives of prostaglandin F with a free C-9 hydroxyl to be prepared in high yield. These served as
2ꢀ
starting materials for synthesizing modified prostaglandins, e.g., 11,15-difluorodideoxy- and 9-fluorodeoxyprostaglandins
F
.
2ꢀ
Temporary protection of the hydroxyl of the cyclopentane ring by conversion to the phenylboronate ester 12 using
phenylboronic acid in dioxane could be used to synthesize the methyl ether of prostaglandin F 15-acetate (14). Ester 12 was
2ꢀ
not isolated but worked up with acetic anhydride and Py in benzene to obtain the prostaglandin (13). Removal of the
phenylboronate protection by treatment with H O produced the desired acetate 14 (Scheme 3).
2
2
O
HO
ii
CO Me
2
CO Me
2
i
9
Ph
B
11
O
HO
OH
OH
1
12
O
HO
iii
CO Me
CO Me
2
2
Ph
B
O
HO
OAc
OAc
13
14
i. PhB(OH) , dioxane; ii. Ac O, Py, DMAP, benzene, 23°C, 18 h; iii. H O , acetone, 60°C, 3 h
2
2
2 2
Scheme 3
Temporary silyl protection, e.g., BDMS ethers, must be used to differentiate hydroxyls in base-labile type
E prostaglandins containing a free carboxyl group.
Thus, prostaglandin E (15) was fully silylated by BDMS-Cl in the presence of imidazole to produce the
2
tert-butyldimethylsilyl ether of 11,15-di(tert-butyldimethylsilyl)prostaglandin E (16). The latter was worked up with HCl
2
solution (1 M) in THF for 5 min. This removed the silyl protection from the carboxylic group and also one of the hydroxyls
and formed a mixture of monosilyl derivatives of prostaglandin E , i.e., 11-tert-butyldimethylsilylprostaglandin E (17a) and
2
2
15-tert-butyldimethylsilylprostaglandin E (17b) with the 15-OH regio-isomer dominating. These were separated by column
2
chromatography over silica gel (Scheme 4). Then, prostanoids 17a and 17b could be converted into the corresponding
fluorodeoxyprostaglandins [9].
O
O
OBDMS
OH
ii
i
O
O
BDMSO
HO
OH
15
BDMSO
16
O
O
OH
OH
+
11
11
15
O
15
O
BDMSO
HO
OH
BDMSO
17a
17b
i. DMF, BDMSCl, imidazole, 25°C, 18 h; ii. THF, 1 M HCl, 5 min
Scheme 4
The presented examples are just some of the possibilities for differentiating the hydroxyls and represent convenient
methods for preparing synthons from natural prostaglandins. Type F prostaglandins are the most versatile for preparing both
natural and modified prostaglandins of other types. Protected prostanoids with one free hydroxyl and orthogonal protecting
groups on the others can be synthesized by using a combination of protecting groups that are selectively introduced or removed.
This can allow conversion to modified type E, D, and I prostaglandins. Type E modified prostaglandins in several instances
293

were more conveniently synthesized from commercially available natural prostaglandins E and E using acid-labile silyl
1
2
ethers. Thus, the synthetic schemes presented above allow protecting groups to be introduced at any hydroxyls of type E and
F prostaglandins.
EXPERIMENTAL
Natural prostaglandins were obtained from the pilot plant of the Institute of Chemistry (Tallin, Estonia).
Morpholinosulfurtrifluoride (MSTF) was synthesized from SF and trimethylsilylmorpholine as described earlier [5].
4
UV spectra were recorded on a Specord UV–Vis instrument (Germany). Fast-atom bombardment (FAB) mass spectra were
recorded on an MS-50TS instrument (Kratos, Great Britain). PMR spectra were taken from CDCl solutions with chemical
3
shifts (ꢂ, ppm) relative to Me Si on a Bruker CPX200 spectrometer (Bruker, Germany) at operating frequency 200 MHz.
4
Rotation angles were determined on a Jasco DIP-360 polarimeter (Japan Spectroscopica Co., Japan). HPLC was performed
on a DuPont 8800 gradient liquid chromatograph (DuPont, USA) equipped with SPD 2A spectrophotometric (Shimadzu,
Japan) and refractive-index (DuPont, USA) detectors connected in series. TLC was carried out on Silufol UV-254 plates
(Kavalier, Czech. Rep.) with detection by phosphomolybdic acid (5%) in alcohol. Column chromatography was performed
using silica gel L (40–100 ꢃm) (Chemapol, Czech. Rep.). The course of the separation was monitored by TLC. Solutions were
evaporated in a rotary evaporator in vacuo (water aspirator) at <30°C (water bath).
General Method for Preparing tert-Butyldimethylsilyl Prostaglandin Derivatives. A solution of silylated
prostaglandin (100 mg) in DMF (1 mL) was stirred, treated with tert-butyldimethylchlorosilane and imidazole calculated for
1.5 equivalents per single silylated group. The mixture was stirred for 18 h at room temperature and diluted with H O (5 mL)
2
and Et O (5 mL). The Et O layer was separated. The aqueous layer was extracted with Et O (3 ꢄ 10 mL). The combined Et O
2
2
2
2
extracts were washed with H O and saturated NaCl solution and dried over anhydrous Na SO . The desiccant was filtered off.
2
2
4
The filtrate was evaporated.
Fluorination of Prostaglandins. MSTF calculated for 1.5 equivalents per single fluorinated group was dissolved in
CH Cl (3 mL) under anAr atmosphere, stirred, cooled to –70°C, treated dropwise with a solution of fluorinated prostaglandin
2
2
in CH Cl , stirred until the reaction was finished (TLC monitoring), treated with saturated aqueous NH Cl solution (3 mL),
2
2
4
left to self-heat to room temperature, and diluted with H O (5 mL). The organic layer was separated. The aqueous layer was
2
extracted with CHCl (3 ꢄ 10 mL). The organic extracts were combined, washed with H O and saturated NaCl solution, and
3
2
dried over anhydrous Na SO . The desiccant was filtered off. The filtrate was evaporated. The solid was purified by column
2
4
chromatography over silica gel.
Methyl Ester of 9,11-Diacetylprostaglandin F (2a) and Methyl Ester of 9,15-Diacetylhydroxyprostaglandin
2ꢀ
F
(2b) from the Methyl Ester of Prostaglandin F . A solution of the methyl ester of prostaglandin F (1, 80 mg) in
2ꢀ
2ꢀ
2ꢀ
anhydrous acetone (1.6 mL) was stirred vigorously at –40°C, treated with trimethylsilyldiethylamine (300 ꢃL), stirred for
40 min at the same temperature, and evaporated to dryness. The residue was evaporated twice with benzene. The light-yellow
oily residue was dissolved in benzene (1 mL), treated with Py (300 ꢃL) and acetic anhydride (600 ꢃL), stirred at room
temperature for 18 h, diluted with cold MeOH, and evaporated to dryness. The solid was dissolved in acetone (1 mL), diluted
with aqueous acetic acid (1 mL, 67%), stirred for 2 h at 40°C, and evaporated. The solid was dissolved in benzene and
chromatographed over silica gel using a benzene:acetone gradient to afford the methyl ester of 9,11,15-triacetylprostaglandin
F
(3, 9 mg), yield 8%; the methyl ester of 9,15-diacetylprostaglandin F (2b, 6 mg), yield 6%, colorless oil, R 0.32
2ꢀ
2ꢀ f
(CHCl :EtOAc, 5:1). PMR spectrum: 5.48 (2H, m, H-13, H-14), 5.25 (2H, m, H-5, H-6), 5.02 (1H, m, H-9), 4.75 (1H, m,
3
H-15), 4.05 (1H, m, H-11), 3.58 (3H, s, CO CH ), 1.92 [3H, s, C(9)OCOCH ], 1.88 [3H, s, C(15)OCOCH ], 0.82 (3H, t,
2
3
3
3
H-20); and the methyl ester of 9,11-diacetylprostaglandin F (2a), 38 mg (39%), colorless oil, R 0.12 (CHCl :EtOAc, 5:1),
2ꢀ
f
3
22
[ꢀ] +11.4° (c 1.04, CHCl ). PMR spectrum: 5.52 (2H, m, H-13, H-14), 5.25 (2H, m, H-5, H-6), 5.08 (2H, m, H-9, H-11),
D
3
3.85 (1H, m, H-15), 3.58 (3H, s, CO CH ), 1.92 [6H, s, C(9)OCOCH , C(11)OCOCH ], 0.80 (3H, t, H-20).
2
3
3
3
From the Methyl Ester of 9,11,15-Triacetylprostaglandin F
.
A
solution of the methyl ester of
2ꢀ
9,11,15-triacetylprostaglandin F (200 mg) [7] in MeOH (5 mL) was treated with K CO (100 mg), stirred for 30 min at room
2ꢀ
2
3
temperature, diluted with H O (10 mL), acidified with HCl solution (1 M), and extracted with EtOAc (3 ꢄ 10 mL). The
2
combined organic extracts were worked up as described above. The solid was dissolved in benzene and purified by
chromatography over silica gel using a benzene:acetone gradient to afford the methyl ester of 9,11,15-triacetylprostaglandin
294

F
(3, 50 mg, 25%); the methyl ester of 9,11-diacetylprostaglandin F (2a, 48 mg, 26%); and the methyl ester of
2ꢀ
2ꢀ
9,15-diacetylprostaglandin F (2b, 89 mg, 49%).
2ꢀ
Methyl Ester of 15-Fluoro-15-deoxyprostaglandin F (4). The methyl ester of 9,11-diacetylprostaglandin F
2ꢀ
2ꢀ
(2a, 80 mg) was fluorinated by MSTF. The resulting fluoride was purified by column chromatography over silica gel using a
benzene:EtOAc gradient to afford the methyl ester of 15-fluoro-15-deoxy-9,11-diacetylprostaglandin F (56 mg, 70%), colorless
2ꢀ
viscous oil, R 0.32 (hexane:Et O, 1:1). Mass spectrum (m/z, I, %): 454 (0.1) [M], 423 (0.3) [M – OMe], 411 (0.5) [M – Ac],
f
2
394 (2) [M – AcOH], 374 (3) [M – AcOH – HF], 334 (31) [M – 2ꢄAcOH], 314 (100) [M – 2ꢄAcOH – HF]. The resulting
fluoroprostaglandin was dissolved in MeOH (10 mL), treated with NaOMe (27 mg) in MeOH, and stirred for 1 h at 40°C. The
excess of NaOMe was decomposed by glacial AcOH. The mixture was evaporated. The solid was suspended in H O (5 mL)
2
and extracted with EtOAc (3 ꢄ 15 mL). The combined organic extracts were worked up as described above. Fluoride 4 was
purified by column chromatography using a benzene:EtOAc gradient to afford the methyl ester of 15-fluoro-15-
deoxyprostaglandin F (4, 41 mg, 63% calculated for 2a), thick colorless oil, R 0.62 (CHCl :MeOH, 10:1). PMR spectrum:
2ꢀ
f
3
5.65 (2H, m, H-13, H-14), 5.42 (2H, m, H-5, H-6), 5.03 (1H, dm, J = 51 Hz, H-15), 4.37 (1H, m, H-9), 4.12 (1H, m, H-11),
HF
3.67 (3H, s, CO CH ), 0.90 (3H, t, H-20). Mass spectrum (m/z, I, %): (bis-trimethylsilyl derivative): 514 (6) [M], 499 (6)
2
3
[M – Me], 443 (29), [M – C H ], 423 (20) [M – C H –HF], 373 (41), [M – 141], 371 (70) [M – 143], 353 (15)
5
11
5 11
[M – C H – MeSiOH], 333 (47) [M – C H – Me SiOH – HF], 129 (100).
5
11
5
11
3
Methyl Ester of 11-Fluoro-11-deoxyprostaglandin F (5). The methyl ester of 9,15-diacetylprostaglandin F
2ꢀ
2ꢀ
(2b, 30 mg) was fluorinated by MSTF. The resulting fluoride was separated as described above to afford the methyl ester of
11-fluoro-11-deoxy-9,15-diacetylprostaglandin F (20 mg, 67%), colorless viscous oil, R 0.23 (hexane:Et O, 1:1). Mass
2ꢀ
f
2
spectrum (m/z, I, %): 423 (0.2) [M – OMe], 396 (2) [M – 58], 394 (1) [M – AcOH], 374 (9) [M – AcOH – HF], 334 (9)
[M – 2ꢄAcOH], 314 (81) [M – 2ꢄAcOH – HF], 117 (100). The resulting fluoroprostanoid was dissolved in MeOH (3 mL),
treated with NaOMe (10 mg) in MeOH, and stirred for 2 h at 40°C. The excess of NaOMe was decomposed by glacial AcOH.
The mixture was evaporated. The solid was suspended in H O (3 mL) and extracted with EtOAc (3 ꢄ 10 mL). The combined
2
organic extracts were worked up as described above. The product was isolated by column chromatography over silica gel
using a benzene:EtOAc gradient to afford the methyl ester of 11-fluoro-11-deoxyprostaglandin F (5, 13.8 mg, 85%),
2ꢀ
23
thick oil, R 0.34 (CHCl :EtOAc, 5:1), [ꢀ] +31.5° (c 0.92, CHCl ), lit. [10] [ꢀ] +32.3°.
f
3
D
3
D
15-Fluoro-15-deoxyprostaglandin F (6). A solution of the methyl ester of 15-fluoro-15-deoxyprostaglandin F
2ꢀ
2ꢀ
(4, 30 mg) in dioxane:MeOH (7 mL, 1:5) was treated with aqueous KOH (5 mL, 40%), stirred for 2 h at room temperature,
acidified with HCl (1 M), and extracted with EtOAc (3 ꢄ 10 mL). The combined organic extracts were worked up as described
above to afford 15-fluoro-15-deoxyprostaglandin F (6, 30.7 mg, 69%), thick oil solidifying at <3°C, R 0.44
2ꢀ
f
22
(toluene:dioxane:AcOH, 40:10:1), [ꢀ] +26.3° (c 0.75, EtOH), mp 130–131°C (tris-hydroxymethylaminomethane salt).
IR spectrum (KBr, film, cm ): 3500, 2960, 2930, 2870, 1740, 1725, 1460, 1440, 1370, 1250, 1170, 1040, 970, 950.
D
–1
PMR spectrum: 5.65 (2H, m, H-13, H-14), 5.42 (2H, m, H-5, H-6), 5.03 (1H, dm, J = 51 Hz, H-15), 4.37 (1H, m, H-9), 4.12
HF
(1H, m, H-11), 0.90 (3H, t, H-20).
Methyl Ester of Prostaglandin F 15-Acetate (14). A solution of the methyl ester of prostaglandin F that was
2ꢀ
2ꢀ
prepared from prostaglandin F (168 mg) in dioxane (10 mL) was treated with phenylboronic acid (170 mg), held for 18 h at
2ꢀ
room temperature and 2 h at 50°C, evaporated, and thoroughly dried in vacuo with an oil pump. The resulting purified
prostanoid 12 was dissolved in benzene (20 mL); treated with acetic anhydride (1 mL), Py (0.5 mL), and
N,N-dimethylaminopyridine (0.5 mg); held for 18 h at room temperature; carefully diluted with MeOH (3 mL); and evaporated
to dryness. The solid was suspended in H O and extracted with EtOAc (3 ꢄ 20 mL). The combined organic extracts were
2
worked up as described above. The resulting acetyl derivative (13) was dissolved in acetone (15 mL) and worked up with
aqueous H O (10 mL, 30%). The mixture was incubated for 3 h at 60°C. The acetone was evaporated. The solid was diluted
2
2
with H O and extracted with EtOAc (3 ꢄ 20 mL). The combined organic extracts were worked up as described above. The
2
mixture of products was separated by column chromatography over silica gel using a CHCl :EtOAc gradient to afford the
3
methyl ester of F (1, 50 mg) and the methyl ester of prostaglandin F 15-acetate (14, 109 mg, 83% considering the
2ꢀ
2ꢀ
22
isolated methyl ester of prostaglandin F , light-yellow oil, R 0.55 (CHCl :MeOH, 10:1), [ꢀ] –4.7° (c 0.875, EtOH), lit.
2ꢀ
f
3
D
[11] [ꢀ] –5.3°.
D
11-tert-Butyldimethylsilylprostaglandin E (17a) and 15-tert-Butyldimethylsilylprostaglandin E (17b).
2
2
Prostaglandin E (15, 100 mg) was fully silylated by BDMS-Cl as described above. The resulting trisilyl derivative (16) was
2
dissolved in THF (2 mL), treated with HCl solution (500 ꢃL, 1 M), stirred at room temperature for 5 min, diluted with HCl
(500 ꢃL, 1 M), stirred at room temperature for 5 min, treated with CHCl (5 mL), and poured into saturated aqueous NaHCO
3
3
295

solution. The organic layer was separated. The aqueous layer was acidified by HCl (1 M) until the pH was 3 and extracted
with EtOAc (3 ꢄ 10 mL). The combined organic extracts were worked up as described above. The mixture of 11- and
15-monosilyl derivatives of prostaglandin E was separated by column chromatography over silica gel using a benzene:EtOAc
2
gradient to afford 15-tert-butyldimethylsilylprostaglandin E (17b, 33.2 mg, 49%), colorless viscous oil, R 0.45 (benzene:EtOAc,
2
f
2:1), mass spectrum (m/z, I, %) (mass spectrum taken as the methyl ester): 480 (0.1) [M], 449 (2.3) [M – OMe], 431 (3.4)
[M – OMe – H O], 423 (100) [M – C H ], 409 (13) [M – C H ] and 11-tert-butyldimethylsilylprostaglandin E (17a,
2
4
9
5
11
2
21.4 mg, 32%), colorless viscous oil, R 0.61 (benzene:EtOAc, 2:1), mass spectrum (m/z, I, %): 480 (0.2) [M], 449 (1.5)
f
[M – OMe], 431 (5.3) [M – OMe – H O], 423 (100) [M – C H ], 409 (20) [M – C H ].
2
4
9
5 11
ACKNOWLEDGMENT
The work was partially supported by State Contract FTsP No. 14.740.11.0810 and an RFBR Grant (Project
No. 09-04-00317a).
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