JPS63190852A - Novel prostacyclins - Google Patents

Abstract

NEW MATERIAL:A compound shown by formula I [R<1> is H, 1-4C alkyl, etc.; R<2> is substituted 5-8 alkyl, (substituted) alicyclic group, etc.; R<3> is H, 2-3C tri 1-7C hydrocarbon-silyl, etc.; asymmetric center of substituted group shown by formula R<2> is R-configuration, S-configuration or a mixture thereof]. EXAMPLE:( 1R,2S,3aS,8aR )-1,2,3,3a,8,8a-Hexahydro-2-hydroxy-1-(1E,3S)-3-hydroxy- 1-octenyl)cyclopent[a]indene-5-acetic acid. USE:Having improving action on blood circulation, antithrombotic action and antitumor action and chemically stable. PREPARATION:A compound shown by formula II (Si- is t-butyldimethylsilyl; THP is tetrahydro 2-pyranyl) is reacted with Wittig reagent to give a compound shown by formula III, which is reacted with propiolic acid to give a compound shown by formula IV and a compound shown by formula Ia is obtained.

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Application Field) The present invention relates to a novel prostacyclin having blood flow improving effect, antithrombotic effect and antiulcer effect.

(Prior art and problems to be solved by the invention) Prostacyclin is known as a natural physiologically active substance, and has a strong platelet aggregation inhibiting effect and a peripheral arterial smooth muscle relaxing effect [Nature, 243
, 443 (/Tough 6)]. Prostacyclin, which has such an effect, is useful for the prevention and treatment of cerebral thrombosis, myocardial infarction, and acute angina pectoris caused by advanced platelet aggregation and increased thrombotic tendency, and is useful for the prevention and treatment of arteriosclerotic diseases. It is expected that it can be applied to treatment, and it is expected that it will be developed as a so-called blood flow improving drug.

Furthermore, prostaglandins, including prostacyclin, are known to have the effect of retaining suppurative mucosa and increasing blood flow in the mucosa, and prostacyclin, which exhibits such effects, can be applied to the prevention and treatment of gastrointestinal ulcers, such as gastric ulcers. It is expected that However, prostacyclin is very unstable, which poses an obstacle to its practical use as a pharmaceutical.

In order to solve this problem, chemically stable prostacyclin analogs have been actively investigated. Examples of chemically stable prostacyclins include carbacyclines in which the oxygen atom at the 6.9-position of prostacyclin is replaced with a carbon atom [JP-A-Sho! Ku/30! [Hiroshi et al.] has been reported.

Furthermore, prostacyclins represented by the following compounds (A) and (B) have been reported as stable prostacyclins that have platelet aggregation inhibitory and antiulcer effects, respectively (J, Am, Chem.
107, 7t&? -ri? 7 Hiro (79g)
.

As a result of extensive research, the present inventors created chemically stable novel prostacyclins and completed the invention.

(Means for Solving the Problems) That is, the gist of the present invention is the following general formula (1) (in the above formula, y is a hydrogen atom: C, -C, a straight chain or branched alkyl group; /equivalent represents one selected from the cations of R1
is an unsubstituted C1 to C8 straight or branched alkyl group; a substituted or unsubstituted alicyclic group; an optionally substituted phenyl group, an optionally substituted phenoxy group, C, 40,
O substituted with an alkoxy group or a cycloalkyl group of O, -C, % 0. alkyl group; C6 to C9
represents a group selected from C5-C1 straight-chain or branched-chain alkynyl groups; Rs is a hydrogen atom; C2-C3 acyl group; triC8-C1 hydrocarbon-silyl group ; Represents seven groups selected from groups that form an acetal bond with the oxygen atom of a hydroxyl group, and the asymmetric center in the substituent represented by R1 is R-configuration, S-configuration, or a mixture thereof. ) is a prostacyclin.

The present invention will be described in detail below. In the above formula (1), R1 is a hydrogen atom; C1 such as methyl, ethyl, n-propyl, isopropyl, D-butyl, etc.
~C4 linear or branched alkyl group; alkali metal cation such as Na", ni+, "/2Ceb"+1/Mg8
+, 1/3A1s+ or trivalent metal cation,
Represents seven cations selected from /equivalent cations such as ammonium ions. R1 is n-pentyl, n-hexyl, /
-) f-rupentyl, λ-methylpentyl, /-dimethylpentyl, /-methylhexyl, cometerhexyl, 1. /-Unsubstituted C, ~C, linear or branched alkyl groups such as dimethylhexyl; substituted or unsubstituted fatty acids such as cyclopentyl, cyclohexyl, --n-propylcyclohexyl, j-n-propylcyclohexyl, etc. cyclic group;
Phenyl, 3-chlorophenyl, 3-trifluorophenyl, phenoxy, darkchlorophenoxy, methoxy,
Methyl, ethyl, n substituted with substituents such as ethoxy, n-furboxy, cyclopentyl, cyclohexyl, etc.
- C0 to C5 alkyl groups such as propyl, isopropyl, n-butyl, θec-phtyl, t-butyl, n-pentyl; 3-hexenyl, derhexenyl, j-hexenyl, /-methyl-5-hexenyl, C, ~ C9 straight chain or Branched alkenyl group (among them, 2,6-dimethyl-S-hebutenyl group is particularly preferred); 3-pentenyl, /~methyl-3
-Pentenyl, -1methyl-3-pentynyl, /-Mef
Represents a group selected from C, to C2 straight chain or branched alkynyl groups such as -3-hexynyl and cometer-3-hexynyl. R'' is a hydrogen atom; acetyl, propiogin tri01-C, alkylsilyl group, diphenyl C1-Q such as t-butyldiphenylsilyl, ,6
-tri-t-butylphenoxy)silyl group, etc.) +7
(, ~C7 hydrocarbon-silyl group; methoxymethyl, /
-ethoxy ether, comethoxyprovil, -monoethoxycoprovil, (comethoxyethoxy)methyl,
Benzyloxymethyl, cochtrahydropyranyl, -
A group that forms an acetal bond with the oxygen atom of a hydroxyl group such as -tetrahydrofuranyl, a-(p-methoxytetrahydropyranyl), Aj-dimethyl-3-oxercooxobicyclo(J, /, θ]hex+-yl, etc. Preferable specific examples of the glostacyclines provided by the present invention are listed below.

(1) (IR,,2S,,7aS,jaR)-/,
Col 3I J a 1g.

fa-hexahydrocohydro 7~/-((/mi9
．． ? and) -3-hydroxy-/-octenyl)cyclopent (a) indene-j-ff[(2)(/Once, once,
3adan, ffadan) -/, ko, 3.3a, g.

II: a-hexahydro-m-hydroxy-/-((/
1.7B, da5)-3-hydroxy-gumethyl-7-
octenyl)cyclobent[a]indene-5-acetic acid (3) (IR, KO8.Jatan, ZaR)-/, KO, J
, ,7ea, g.

ffa-hexahydrocohydroxy-/-((/
'! ,, Jdan)-3-hydroxy-3-cyclohexyl-/-propenyl)cyclobent (a) indene-3-
Acetic acid (4) (IR,Q,,7aS,zaR)-/,2,
3.3a+g+ta-hexahydrocohydroxy-
/-((/b, 3訃DAdan)-3-hydrocedarmethyl-l-octen-6-yl)cyclopent(a) indene-3-acetic acid (5) Methyl of the above (1) to (4) ester (6)
Ethyl ester (7) of the above (1) to (4) above (
1) to (4) t-butyl ester (8) above (5)
) -t-butyldimethylsilyl ether (9) Co(tetrahydrocopyranyl) ether αO of (5) above Sodium salt of (1) to (4) above (1)
Potassium salts of ~(4) (2) Ammonium salts of 1Je (1) ~ (4) Next, the method for producing the compounds of the present invention will be described (0 above general formula CI)
The compound of the present invention represented by, for example, the aS Organic Synthesis Symbodicum (organized by the Organic Synthetic Chemistry Society) VS Abstracts Collection, 1
/-,! It can be produced by the route shown below using the already known compound [Kawa] described below along with its synthesis method on page 1# as a starting material.

The lyl group, THP, represents a tetrahydrocobyranyl group. ) OTHP
0T) LP(II) (111
1(IV) (V)○THPO
THP (Vl) (Vll)OTH
P0THP(Vll)
(■)OTI(P
0THP [X] [Enter] [Store] (la) Step 1 is a step of reacting Compound (II) with Wittig's reagent to obtain Compound (fit). As a Witteitz reagent, methoxymethyltriphenylphosphonium chloride is combined with sodium hydride or potassium tert-
Preference is given to Witteitsch's reagent obtained by the action of a base such as butoxide. The reaction is usually carried out in an ether such as ethyl ether or tetrahydrofuran; dimethyl sulfoxide; or a mixed solvent thereof at a temperature of θ°C to a7
Perform at 17°C. Step 1 is the compound [l11),! : Ethyl gproolate, by Thiels-Alder reaction,
This is a step to obtain compound (IV). The reaction is carried out in an aromatic hydrocarbon such as toluene or benzene or without solvent.
It is carried out at izo°C to -30°C. Step 3 is compound CI
! /), such as lithium aluminum hydride,
Compound (V
). The reaction takes place in an ether solvent such as ethyl ether or tetrahydrofuran at -qO°C~! θ℃
It will be held in Step d is a step of oxidizing compound (V) to obtain aldehyde [■]. In the oxidation reaction, an oxidation method using a triethylamine-sulfur trioxide/pyridine complex-dimethyl sulfoxide system is particularly preferred. The reaction temperature is usually lO<0>C to lIO<0>C, and the amount of the brewing agent used is preferably 2 to 100 times the molar excess. Step 3 is a step of reacting Compound (Vl) with Witteitsch's reagent to obtain Compound [■]. The Wittig reagent is preferably a Wittig reagent obtained by reacting with a base such as sodium methyltriphenylphosphonium bromide dihydride or potassium tθrt-butoxide. The reaction is carried out in ethers such as ethyl ether and tetrahydrofuran, or dimethyl sulfoxide, usually at θ°C to IIo°C. Step 6 is a step in which the compound [■] is subjected to hydroboration and then oxidized under alkaline conditions to obtain the compound [Saul]. A sterically bulky reagent is preferable as a hydroporation agent. -BBN and dicyamylborane are particularly preferred. The reaction is carried out in an ether such as tetrahydro7-), usually at -30°C to θ°C, and then oxidation under alkaline conditions is particularly preferred. J-Aqueous caustic soda solution and 30% hydrogen peroxide solution are used, and the test is carried out at θ°C to 30°C. Step 7 is to oxidize the compound (■) and then esterify it to form the compound (IX)
Pyridinium dichromate (PDO) is preferable as the Oat-forming agent used in the step of obtaining , and the process is carried out in dimethylformamide. The reaction temperature is usually -20°C to Hirotheta°C. For esterification, an ether solution of diazomethane is
It is carried out by acting at temperatures between .degree. C. and room temperature. The step is a step of desilylating compound (IX) with a fluorine compound such as tetrabutylammonium fluoride or cesium fluoride. The reaction is usually carried out at θ°C to 30°C in an ether such as tetrahydrofuran or ethyl ether.
It will be held in Step D is a step of oxidizing the hydroxymethyl group of compound (X) to obtain compound [yJ]. As the oxidizing agent, an amine-pyridine sulfur trioxide complex-dimethyl sulfoxide system is particularly preferably used.

The reaction temperature is usually io°C to qo°C, and the reaction time is about 1 minute to 1 hour. 0th step IO is compound (XI) K,
(R'O), P(0)CH,C! (0)-R" (wherein, R2 is the same as R3 in structural formula (1), and R4 represents a C, 40, alkyl group) is reacted with a Witteitsch reagent obtained by treating with a base. Therefore, as the zero base in the step of obtaining the compound [Kari], sodium hydride, potassium hydride or potassium tart-butoxide is preferable, and 1 of the Witteitz reagent is /-, 1/1
is preferred. The reaction is carried out in an ether such as tetrahydrofuran or dimethoxyethane at -0°C to 30°C.

Step // is a step in which compound (la) is obtained by reducing compound (1). As reducing reagents, for example trialkylborohydrides such as sodium borohydride, zinc borohydride, diphenyltin hydride or lithium tri5ea-butylborohydride;
J, diisobutylaluminum hydride modified with 4-di-tert-butyl methylphenol; or/, lithium aluminum hydride modified with /-beconaphthol and a lower alkyl such as ethanol, etc. can be mentioned.

As a reaction solvent, lower alcohols such as methanol and ethanol; ethyl ether, etc. Ethers such as hydrofuran and dioxane; aromatic hydrocarbons such as benzene or toluene. The amount of reducing reagent to be used is preferably /~IO equivalent with respect to compound (l). The reaction is carried out at -100°C to 30°C. This is the step of removing the compound (lb) to obtain compound (lb). The reaction is preferably carried out using acetic acid, a pyridinium salt of p-toluenesulfonic acid, a cation exchange resin, or the like as a catalyst, and a solvent such as water, tetrahydrofuran, ethyl ether, dioxane, acetone, acetonitrile, or the like. The reaction is usually -7
The heating is carried out at g°C to g0°C for about 10 minutes to 3 days. Process/3
is the compound (lc) by hydrolyzing the compound (It)
). The reaction is carried out in a single or mixed solvent of water, methanol, or ethanol containing sodium hydroxide at -10°C to IOO°C, or alternatively, using an enzyme such as lipase, in water or a solution containing water. It is carried out at -10°C to 60°C. The produced compound (1) is subjected to a salt-forming reaction to give the corresponding carboxylic acid salt, if necessary. , sodium hydroxide, ammonia, triethylamine, morpholine, etc. in a conventional manner.

(Effect of the invention) The glostacyclines of the present invention are chemically stable,
It is also expected to have excellent pharmacological effects.

(Example) The present invention will be explained in more detail with reference to Examples below.
The present invention is not limited to the following examples unless it exceeds the gist thereof.

Reference example 1 0THP 0TH
P Otsu 60% sodium hydride under a miargon atmosphere/! r t
I (39,!r mmol) in DMSO/0-
Suspended in? After cooling to room temperature, stir for 1 min at 0 °C.
Methoxymethyltriphenylphosphonium chloride/
3.3; Drop a DMSO solution of I (39, dammol) -〇- and stir for an additional 30 minutes. Next, 30 g of a THF solution of the formyl compound/JI (7,9 mmol) was added, and after reaction at room temperature for 1 min, saturated NH,C
Add aqueous solution and extract with ethyl ether. The extract was washed with saturated saline and anhydrous Mg5O.

After drying, the solvent was distilled off under reduced pressure.The resulting residue was subjected to silica gel column chromatography to obtain the enol ether ff Ii (7%) as a colorless oil.

Engineering R (liquid film method) Niji maz; 3030. /b! ! r
, /A/7. /4'zaθ, /yu7ko.

//, 3! r, 10 Dada, 997. Guri 3,79 pieces tM
-'NMR (CDCI,) δ (ppm); A, 47 (d
, /AH2,0,jH), 1ffjfd.

//Hz, O, jH), j', A de (d, #Hz.

o, sH), r, bθ (broad s, Q, jH).

j, 11. ? (broad e, 0.SH), Iθθ
(d, //Hz, Q, jH), u, 63 (m, /H).

ri, /θ-7.10(m, /zaH),,? , A/(s.

372H), J, t! ; (8, 3/2H)
, θ6 (s, qH), 0.0 (s, AH) Reference example Cotoluene lO-, to the enol ether form gg (K II
mmol) and 0 ethyl furopiolate (/u
, 3 mmol 1) into a stainless steel reaction tube and seal it.
React at 200°C for 10 hours. After cooling, toluene is distilled off under reduced pressure, and the residue is subjected to silica gel column chromatography to obtain the ester l/, jψ# (?#%) as a colorless oil.

Engineering R (liquid film method) Niji max; Co940. /7ko/,/
40 de, /! 10, /ko10°/240. //Here, IO? -0. /θ30. Zada-2゜7g-piece-1 NMR (CDCI,)'! '(ppm): ? , 7A(
m, JH), 7.1. t(m,/H).

44.57 (m, /H), Q,, 7/(q, A, KoH
z.

2H), lA, 10-/, 10(m, /IIH).

/, J2(t, 6.Hz,, 7H), θ, ffA(s
.

? H), 0.03 (a, AH) Reference Example 3 Under argon atmosphere, LiAIH, 2! Orq(&, 4
/mmol) in ether suspension! The ester form J/, j! is added to rgIt under ice-cooling. r I (J, J mm
Add dropwise 10 d of an ether solution of ol) and stir for 1 hour. After the reaction is complete, add water! Add Rl, 04&, stir for 30 minutes, and pour over Celite. The residue is further extracted with ether, the extract is concentrated under reduced pressure, and the residue is subjected to silica gel column chromatography to obtain alcohol 4/,/dy (Ii).

IR (liquid film method) maz; JJ /θ, -ta! 0
, /! ! :θ, /1I70. /29.

//Here, 107! , 103! , 102! , gdaO17
t0ffl-' NMR (apel,) δ (ppm); 7, J?
-7,0,7(m,,7H), u,+ko(m+/H)
, Hiroshi, 3θ-Hako O(m, #H).

j, 70 (s, koH), 0.90 (e, 9H).

0.0II (B, 6H) Reference example alcohol -g Otq (o, l, j mmol
), triethylamineco, cotnl and DMSO, 7
In the solution of g1st, trioxide ion, pyridine complex/,
Cologne (wa, ? mmol) ODMSO solution solution chamber -
and stirred for an additional 70 minutes. Pour the reaction solution into ice water and extract with ether. The extract is washed with water and saturated brine, and dried over anhydrous MgSO4.The solvent is distilled off under reduced pressure to obtain an aldehyde core.The obtained aldehyde is used in the next step without purification.Reference Example! 0T) rP yo 0THP A Under argon atmosphere, methyltriphenylphosphonium bromide 7
Anhydrous THF suspension of 10η (9 mmol)
potassium t-butoxide (tBuOK) at room temperature.
A solution of CocoOwq (/de&mmol) in anhydrous THF is added and stirred for an additional 75 minutes. After cooling with water, an anhydrous THF solution containing 0.0 kg of aldehyde compound was added, and the mixture was stirred at room temperature for 30 minutes. Add saturated NH, C1 aqueous solution and extract with ether. The ether extract was washed with saturated saline and anhydrous Mg80. After drying, the solvent was distilled off under reduced pressure. The obtained residue was subjected to silica gel column chromatography to obtain olefin 52!2W9C9/%C'l)
) is obtained as a colorless oily substance. fO,/A2
g, /! 170. /240゜1oto, tda0+ 71OfMS-1HMR(C!DC!1.)δ
(ppm): 1lr-7,00Crn, 3H)
, 1Aff (dd.

/6. ri, 10.3H2,jH),! ;, A, 3 (6°/A, 7H2, jH), ! , /3(eL, 10..3
H2゜jH), 11. 'IO-/, ko0(rn,/zaH).

0, gA (s, 9H), 0.0 da (8, le H) Reference example 6 Under argon atmosphere, olefin 6 da 9 da cape (/, /!
r mmol) in THF solution 5- at 0°C. −
BBN Co, ga 11 (/ /, Ammol) T
HF solution 20- is added dropwise and stirred at room temperature for 7 hours. Then under water cooling, AN sodium hydroxide 3.96- and 30%
Add hydrogen peroxide solution and qj-, and after stirring at room temperature for several hours,
The ether layer extracted with ether is saturated with Na, S, O,
After washing with an aqueous solution, saturated NaHCO, an aqueous solution, and saturated salt/water, and drying over anhydrous Mg804, the solvent was distilled off under reduced pressure. The residue was subjected to silica gel column chromatography to obtain alcohol Z 4', 7.1'ηCt! %') as a colorless oil.

Engineering R (liquid film method) Niji maz: J4'jθ, ko9ri0.
160g, /! 10°/ko1,0. 10zaOo
za"0*"'OIMI-1NMn<cDcl,)
δ (ppm): ? , Ko3-19.2 (m, jH)
, 11.40<m.

jH), lt,, 20-/, IOCm, 23H).

Oozag (s, ni), O, O,? (8,AH) Reference Example 7 Alcohol 7379rIIICO,t! r mmo
l) in DMF solution 4(d) at room temperature with PDC (Pyr
iainiumDichromate) 7.9'I
Add I (1/b mmol) and stir for 1 hour. Next, the mixture is extracted with ether, washed with water, dried over anhydrous Mg5O, and then the solvent is distilled off under reduced pressure. The residue obtained is treated with an ethereal solution of diazomethane. Esterification was confirmed by thin layer chromatography (TLC), extracted with ether, excess diazomethane was decomposed with formic acid, washed with saturated NaHCO, aqueous solution, and saturated brine, dried over anhydrous MgSO4, and the solvent was distilled off under reduced pressure. leave The obtained residue was subjected to silica gel chromatography to obtain the ester j 3uOwq (t
a%) as a colorless oil.

1 (liquid film method) Niji maz: -19! rO,/ri,y
t, icojf, //lIO.

Off1-'NMR (cD
cl, ') δ (ppm); 7. Koku - 6.9 meters,
, 7) Ri, 11. lt(m.

jH), J, A3 (Japanese, 7H), j, jtI (s
.

koH), Q, JO-HakoO(m, /ff)i).

O, A7 (s, jH), 0.03 (e, LH) Reference example Under argon atmosphere, ester form t/21! Cape (+!7.
．． 27 mmol) of TI(F solution l- at room temperature, add 540 mm of dBu4N F'rHF solution (/M), add 0 saturated aqueous NH40X solution and stir for 2 hours,
Extract with ether. The ether layer was dried over anhydrous Mg5O, and the solvent was distilled off under reduced pressure. The residue was subjected to silica gel chromatography, and the alcohol content was analyzed using vH! (r/s)
is obtained as a colorless oil.

Engineering R (liquid film method) Niji max; 5IIbo, Ko940
．． /ri32. /4cJg.

1,0. // Octopus * / (7J !r Q
n-”NMR (CD(n,)δ(ppm) near, co0-
7.00Cm, 3H'), 11.4ko (m.

/H), Tei 8.2θ-810 (m, /deH).

,? , 4j (8, JH), , 7. jff(s, JH)
Reference example DE 0 THF grass 0 THP Q Under argon atmosphere, alcohol body grass Coco θ ~ (θ, j 3 mmol
) and triethylamine are dissolved in anhydrous DMEIO eight. Anhydrous DM of SO, pyridine complex/071
Add to the SO solution and stir at room temperature for 70 minutes. Pour the reaction solution into ice water and extract with ether. The extract is anhydrous
After drying with g5O, the solvent was distilled off under reduced pressure to obtain aldehyde 1.
0//! I got r■. The product thus obtained was used in the next step without purification.

Reference Example IO Under argon atmosphere, 60% sodium hydride J 0.0
1Ni (0,r Ommol) in anhydrous THF solution, dimethyl (2-oxoheptyl)phosphonate)
/ / Qlq (0,!r/mmol) anhydrous'
Add 1'HF solution lI- and stir for 30 minutes at room temperature.
Next, aldehyde body 10//! Add the anhydrous TRIF solution of R-1 and stir at room temperature for 7 hours. The reaction solution is diluted with saturated NH
Pour into 4Cl aqueous solution and extract with ether. Wash the 0 extract with saturated saline, and add anhydrous Mg80. After drying with
0 IR (9 membrane method); Shim61: 2 lights 0. 173g, /
47 (7, /AJff.

lirigO, /1IIIko, /21aO, //dakod1
NMFj (0DC1,) δ (ppm): 't, 33-
! ;, tza(rn,!rH), +, sq<m.

/H), Il, tO-/, /12(m, λJH).

3.6 (81jH), 3. ! ;3<8. YuR).

0.90 (t, u, gH2,3) () Example 1 H, C00Cn α, β-unsaturated kedoa/j90. g■(0,commol
) is dissolved in Menolco, excess sodium borohydride is added with -CoSC, and the mixture is stirred for 7 hours. After adding acetone to stop the reaction, add a saturated Nu, C1 aqueous solution. After distilling off the methanol, extract the remaining aqueous layer with ether. After distilling off the solvent under reduced pressure, crude alcohol G is obtained. This crude alcohol was dissolved in a 43% acetic acid aqueous solution, and heated and stirred at SOC for 2 hours. After cooling the reaction solution, NaHOOs
In aqueous solution, extract with ethyl acetate, anhydrous Mgso4
and evaporate the solvent under reduced pressure. The obtained residue was subjected to silica gel column chromatography to obtain a highly polar component. α-diol body/! 3! ! (Hiro 7%) obtained as a colorless powder O m, p, 9! rJ-97,0℃ IR (KBr): ν; 3 Da/g, Co17,
/72! , /'f37, /245.

ax //! 3,10za0,10koO,de? 6ffi-'N
MR (CDC13) δ (ppm): 7. /! (d, ri, Al1./H), 7.09CB+/) ri, ? ,07
(eL, ?, 6H2, /H).

1Aj-I! f7 (m, 2) 1), Hiro, // (m.

/H), J, 94Bm, /H), j, 6? (s.

, 7H), 3.40 (8, KoH), 3. OII(m
.

/H), 2.72 (m, 2H) + ko, Sri (m
.

/H), 8i (m, /H), /, 7g-/, 1g (m
, /JH), 0.90Ct, A, gHz, JH) Example co/jα-diol body/, ? J 1 W9C0,01
, mmol) was dissolved in 04 KOH aqueous solution-methanol (/:/) 2rd and stirred at room temperature for an hour.

The mixture was then neutralized with 5N hydrochloric acid, filtered to pHJ-41, and extracted with ethyl acetate. After drying with anhydrous MgSO4, the solvent was distilled off under reduced pressure, and the resulting residue was recrystallized from acetone-n-hexane to give carboxylic acid/! Obtain lzaq (7g%).

m, p, /u/-/eλC (acetone-n-
hexane) Engineering R (KBr): ν. , x;
3330,29. It, /7IIO, /47ri, /3!
3°/30/, /2170,106ri,97ko,9θ
, tffl-'NMR(apels)J(ppm):
7.1tt(a,?,7H2,/H), q,to(e
.

/H), 7.0t (d, 7.Hz, /H).

! r,! rt-! r, lIAcm, IH), 11.0
1cm.

/H), ,? , de(7(m,/H), ,3.!
rgc8゜koH), ,7.5j(m,/H), 3.
0λ(m +/H), 70(m, , 2H), 2
．． 5 (m + / III), 1.90 (m, /H),
/, 4 pieces one box g (m, /JH), 0. Deco (t,
A.? H! ,,7H)Mass (m/I);
311OCM -H,O), 3 here (M -JH
, O).

Ko96. λ6de, =41da, 2coro, /7hiro.

/da/, 9de, It3 Sender: Mitsubishi Chemical Industries, Ltd. Representative patent attorney Hase side - 1 other person

Claims (1)

[Claims] The following general formula [I] ▲There are mathematical formulas, chemical formulas, tables, etc.▼...(I) (In the above formula, R^1 is a hydrogen atom; C_1 to C_4 linear or branched alkyl group ; Represents one selected from 1 equivalent of cation; R^2 is an unsubstituted C_5 to C_8 straight or branched alkyl group; a substituted or unsubstituted alicyclic group; an optionally substituted phenyl group; group, optionally substituted phenoxy group, C_1 to C_2 alkoxy group or C_
C_1 substituted with 5-C_6 cycloalkyl group
~C_5 alkyl group; C_6 to C_9 linear or branched alkenyl group; C_5 to C_7 linear or branched alkynyl group; R^3 is a hydrogen atom;
C_2 to C_3 acyl group; triC_1 to C_7 hydrocarbon-silyl group; represents one group selected from the group that forms an acetal bond with the oxygen atom of the hydroxyl group, and the asymmetric center in the substituent represented by R^2 is R - configuration, S-configuration or a mixture thereof. ) Prostacyclins represented by.