JPH05117230A - Prostaglandin derivative - Google Patents

Abstract

PURPOSE:To obtain a new prostaglandin derivative, capable of powerfully suppressing agglutination of human blood platelet induced with adenosine diphosphate (ADP) and treating various diseases including peripheral circulatory disorder with hardly any induction of diarrhea. CONSTITUTION:A prostaglandin derivative expressed by formula I [R<1> is H, 1-6C alkyl or allyl; R<2> is 5-10C branched aliphatic hydrocarbon; (n) is 4-8], e.g. (17S)-17,20-dimethyl-13,14-didehydro-PGE1 methyl ester. The compound expressed by formula I is obtained by reacting, e.g. a compound expressed by formula II (R<3> is protecting group of OH) with a compound expressed by formula III (R<4> is R<3>), providing a compound expressed by formula IV, then reacting the resultant compound with a compound expressed by formula V (R<5> is R<1> except H), providing a compound expressed by formula VI, subsequently treating the prepared compound with an acid, affording a compound expressed by formula VII and then removing the protecting group or further hydrolyzing the ester.

Description

[Detailed description of the invention]

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to novel prostaglandin (hereinafter abbreviated as PG) derivatives.

[0002]

2. Description of the Related Art Since PG exerts various important physiological actions even in a very small amount, natural PG and a large number of its derivatives have been synthesized and examined for their biological activities with the intention of applying them to medicine. Among them, PGE ₁ has a platelet aggregation inhibitory effect,
It has a characteristic action such as blood pressure lowering action and is practically used as a medicine to improve peripheral circulatory disorders.
E ₁ derivatives have also been investigated. By the way, one of PGE ₁
13,14- with double bonds at positions 3,14 changed to triple bonds
13,14-didehydro PGE ₁ methyl ester and the like are known as didehydro PGE ₁ analogues.

[0003]

SUMMARY OF THE INVENTION The present invention is a conventional PGE.
It is an object of the present invention to provide a novel PGE ₁ derivative which is superior in efficacy to PGE ₁ derivatives and has reduced side effects.

[0004]

SUMMARY OF THE INVENTION The present invention provides the formula

[0005]

(In the formula, R ¹ is a hydrogen atom, has 1 to
6 alkyl groups or allyl groups, R ² represents a branched aliphatic hydrocarbon group having 5 to 10 carbon atoms, and n is 4
indicates an integer of ~8. ) and salts thereof.

[0007] In the present invention, the C 1-6 alkyl group means a straight or branched chain, such as methyl, ethyl, n-propyl, isopropyl, n- butyl group, isobutyl group, t-butyl group, n
-pentyl group, isopentyl group, and the like. A branched aliphatic hydrocarbon group having 5 to 10 carbon atoms is an aliphatic hydrocarbon group having a branch at the α- or β-position thereof, and specifically a branched chain alkyl group (e.g., 1-methyl pentyl group, 2-methylpentyl group, 1-methylhexyl group, 2
-methylhexyl group, 2,4-dimethylpentyl group, 2
-ethylpentyl group, 2-methylheptyl group, 2-ethylhexyl group, 2-propylpentyl group, 2,6-dimethylheptyl group, etc.), cycloalkyl group (e.g., cyclopentyl group, cyclohexyl group, cycloheptyl group, etc.), cyclo an alkyl group having 1 or 2 carbon atoms substituted with an alkyl group (e.g., a cyclopentylmethyl group,
cyclohexylmethyl group, cycloheptylmethyl group, cyclopentylethyl group, cyclohexylethyl group, cycloheptylethyl group, etc.), branched alkenyl group (for example, one of the single bonds at any position in the above branched alkyl group is a double bond, such as a 2,6-dimethylhept-5-nyl group), a branched alkynyl group (e.g., one of the single bonds at any position in the above branched alkyl group is a triple bond, such as 1-methylpent-3-ynyl group, 1-methylhex-3-ynyl group, 2-methylhex-3-ynyl group).

The compounds of formula (I) can be readily prepared, for example, by the methods given below.

[0009]

[0010]

(In the reaction formula, R ³ and R ⁴ are the same or different and represent a hydroxyl-protecting group, and R ⁵ is R ¹ excluding a hydrogen atom.)
and R ² and n are as defined above. Here, the hydroxyl-protecting group is one commonly used in the field of prostaglandins, such as t-butyldimethylsilyl group, triethylsilyl group, phenyldimethylsilyl group,
Examples include a tetrahydropyranyl group, a tetrahydrofuranyl group, a methoxymethyl group, an ethoxyethyl group, and a benzyl group. ) That is, the compound of formula (II) is reacted with the compound of formula (III) to introduce the ω-side chain of PG to give the compound of formula (IV). This is reacted with the compound of formula (V) to give PG
is introduced to give a compound of formula (VI). This is then treated with acid to give compounds of formula (VII). Subsequently, the protective group is removed to obtain a compound of formula (I) in which R ¹ is an alkyl or allyl group having 1 to 6 carbon atoms. Further hydrolysis of this ester yields a compound of formula (I) in which R ¹ is a hydrogen atom.

The compounds of this invention are administered orally or parenterally such as intravenously or intrarectally. As dosage forms for oral administration, for example, solid preparations such as tablets, granules and capsules, and liquid preparations such as solutions, fat emulsions and liposome suspensions can be used. As preparations for intravenous administration, aqueous or non-aqueous solutions, emulsifiers, suspensions, solid preparations dissolved in a solvent for injection immediately before use, and the like can be used. In addition, dosage forms such as suppositories can be used as preparations for rectal administration, and pessaries and the like can be used as preparations for intravaginal administration. The compounds of the invention are α, β, or γ
- It can be formulated by forming an inclusion compound with cyclodextrin, methylated cyclodextrin, or the like.

[0013]

INDUSTRIAL APPLICABILITY The compounds of the present invention strongly inhibited ADP-induced aggregation of human platelets. It also significantly inhibited ADP or collagen aggregation of platelets collected 4 hours after oral administration to guinea pigs, and diarrhea was hardly observed at this time. When administered intravenously to anesthetized dogs, a sustained hypotensive effect was observed. As described above, the compound of the present invention hardly induces diarrhea, which is the most serious problem in PG, at a dose that exhibits a definite pharmacological action, and is therefore useful as a drug for treating various diseases including peripheral circulatory disorders. be.

[0014]

EXAMPLES The present invention will now be described in more detail with reference to examples. Note) During the naming of compounds, for example, "17, 18, 19, 20
"Nor", such as "-tetranol", means that there is no carbon chain at that position (in the case of the example, it means that there is no carbon chain at positions 17-20), e.g. −
``Homo'', like ``dihomo'', means that there are many carbon chains at that position (in the case of the example, it means that there are two carbon chains 2a and 2b between the 2nd and 3rd positions. do.).

Example 1(17S)-17,20-dimethyl-13,14-dide
Hydro-PGE 1methyl ester (1) (3S,5S)-3-(t-butyldimethylsilyl
Xy)-5-methylnon-1-yne (3.85 g) was added to the base.
Dissolve in 28.8 ml of benzene and dissolve in n-butyllithium at 0°C.
(1.95 M, hexane solution, 6.4 ml) was added,
The mixture was stirred at the same temperature for 30 minutes. Diethyl
Aluminum chloride (0.97 M, hexane solution, 1
4.8 ml) was added, the temperature was raised to room temperature, and the mixture was stirred for 30 minutes.
rice field. (4R)-2-(N,N-Diethyl) was added to this solution at room temperature.
amino)methyl-4-(t-butyldimethylsiloxy)
c) cyclopent-2-en-1-one (0.25M,
Benzene solution, 38.4 ml) was added and stirred for 15 minutes.
rice field. The reaction mixture was hexane (100 ml)-saturated ammonium chloride.
sodium solution (100 ml)-hydrochloric acid solution (3M, 30
ml) mixture with stirring, then separate the organic layer
and washed with a saturated aqueous sodium bicarbonate solution (50 ml). obtained
The residue obtained by drying and concentrating the organic layer was filtered through a silica gel column.
Chromatography (developing solvent; hexane: ether
= 10:1) to give (3R,4R)-2-methylene
-3-[(3'S,5'S)-3'-(t-butyl dimer
tylsiloxy)-5'-methylnon-1'-ynyl]-
4-(t-butyldimethylsiloxy)cyclopentane-
3.72 g of 1-one was obtained.

(2) To 5-carbomethoxypentylzinc(II) iodide (0.86M tetrahydrofuran solution, 6.70ml, 5.76mmol) at -70°C was added copper(I) cyanide.lithium dichloride (1.26g). , 7.
20 mmol) in tetrahydrofuran solution (7.20 m
l) was added and stirred at the same temperature for 15 minutes. -7 to this solution
The compound obtained in (1) above (1.42 g, 2.88
mmol) and trimethylsilyl chloride (0.65
8 ml, 5.18 mmol) in diethyl ether (10 ml) was added, and the temperature was raised to room temperature over about 2 hours while stirring. A saturated ammonium chloride aqueous solution (43 ml) was added to the reaction solution, and the mixture was extracted with n-hexane. The organic layer was washed with saturated brine, dried and concentrated, and the resulting residue was washed with ether-isopropyl alcohol (1:4, 14.4).
ml), p-toluenesulfonic acid pyridine salt (36.2 mg, 0.144 mmol) was added, and the mixture was stirred at room temperature for 12 hours. Ether (50 ml) was added to the reaction solution.
and saturated aqueous sodium bicarbonate solution (10 ml) for extraction, the organic layer was dried and concentrated, and the resulting residue was subjected to silica gel column chromatography (developing solvent: n-hexane:ether=4:1) (17S)-. 17,20
-Dimethyl _- 13,14-didehydro-PGE1 methyl ester 1.19 g of 11,15-bis(t-butyldimethylsilyl ether) are obtained.

(3) The compound (536m
g, 0.861 mmol) to acetonitrile (29 m
l) and dissolved in 50% aqueous hydrofluoric acid solution (6.
9 ml) was added. After stirring for 90 minutes at 0° C., the reaction mixture was poured into ethyl acetate (40 ml) and saturated aqueous sodium bicarbonate (245 ml). Extract with ethyl acetate, wash with saturated aqueous sodium bicarbonate solution and saturated brine,
The residue obtained by drying and concentration was subjected to silica gel column chromatography (developing solvent; ethyl acetate: methanol = 4
0:1) to give 320 mg of the title compound.

¹ H-NMR (CDCl ₃ , 300 MHz)
δppm: 0.82-0.96 (m, 6H), 1.07
~1.85 (m, 19H), 2.16 ~ 2.33 (m,
2H), 2.29 (t, J=7.4 Hz, 2H), 2.
62 (ddd, J=1.8Hz, 8.4Hz, 11.3
Hz, 1H), 2.73 (ddd, J=1.1Hz,
7.2Hz, 18.4Hz, 1H), 3.65(s, 3
H), 4.25-4.35 (m, 1H), 4.46 (d
t, J = 1.5Hz, 7.1Hz, 1H) IR (neat): 3400, 2920, 2230, 1
730, 1440, 1160 cm ^-1

The following compounds were obtained in the same manner as in Example 1.

[0020](16RS)-16,20-dimethyl-1
3,14,18,18,19,19-hexadehydro-
PGE1methyl ester ¹ H-NMR (CDCl₃, 300 MHz) δppm:
0.98-1.14 (m, 6H), 1.20-2.42
(m, 17H), 2.26 (t, J=7.8Hz, 2
H), 2.62 (t, J = 10.0 Hz, 1H), 2.
73 (dd, J=7.1Hz, 18.4Hz, 1H),
3.65 (s, 3H), 4.25-4.36 (m, 1
H), 4.37-4.47 (m, 1H) IR (neat): 3400, 2920, 2850, 2
320, 1750, 1700, 1435, 1320, 1
160, 1075, 1010 cm^-1 (17R)-17,20-dimethyl-13,14-dide
Hydro-PGE 1methyl ester ¹ H-NMR (CDCl₃, 300 MHz) δppm:
0.80-0.98 (m, 6H), 1.08-1.86
(m, 19H), 2.16-2.35 (m, 2H),
2.31 (t, J=7.4Hz, 2H), 2.55~
2.81 (m, 1H), 2.74 (dd, J = 7.0H
z, 18.2Hz, 1H), 3.67(s, 3H),
4.26-4.53 (m, 2H) IR (neat): 3390, 2930, 2860, 2
240, 1740, 1460, 1260, 1170, 1
070,730 cm^-1

[0021]17,18,19,20-tetranol-1
6-cyclohexyl-13,14-didehydro-PGE
1methyl ester ¹ H-NMR (CDCl₃, 300 MHz) δppm:
0.80-1.98 (m, 23H), 2.10-2.4
5(m, 2H), 2.31(t, J=7.3Hz, 1
H), 2.62 (t, J=9.8Hz, 1H), 2.7
3 (dd, J=7.1Hz, 18.3Hz, 1H),
3.71 (s, 3H), 4.20-4.35 (m, 1
H), 4.45 (t, J=6.8Hz, 1H) IR (neat): 3450, 2940, 2320, 1
735, 1720, 1450, 1250, 1160, 8
35cm^ー1 (17RS)-20-nor-17-methyl-19-
(2'-methylprop-1'-enyl)-13,14-
didehydro-PGE 1methyl ester ¹ H-NMR (CDCl₃, 300 MHz) δppm:
0.95 (d, J=6.4Hz, 3H), 1.13~
1.86 (m, 15H), 1.60 (s, 3H), 1.
68 (s, 3H), 1.92-2.07 (m, 2H),
2.17-2.35 (m, 2H), 2.30 (t, J =
7.5 Hz, 2H), 2.60-2.68 (m, 1
H), 2.75 (dd, J=7.1Hz, 18.4H
z, 1H), 3.66 (s, 3H), 4.28-4.3
7 (m, 1H), 4.42-4.53 (m, 1H),
5.09 (t, J = 6.2Hz, 1H) IR (neat): 3380, 2920, 2220, 1
750, 1430, 1160, 1070, 830, 72
0 cm^-1

[0022](17S)-17,20-dimethyl-1
3,14-didehydro-PGE1n-butyl ester ¹ H-NMR (CDCl₃, 300 MHz) δppm:
0.78-0.99 (m, 9H), 1.05-1.85
(m, 23H), 2.14-2.35 (m, 2H),
2.27 (t, J=7.9Hz, 2H), 2.56~
2.69 (m, 1H), 2.73 (dd, J = 7.2H
z, 18.4 Hz, 1H), 4.05 (t, J = 6.6
Hz, 2H), 4.24-4.34 (m, 1H), 4.
45 (t, J=6.6Hz, 1H) IR (neat): 3400, 2930, 2320, 1
735, 1720, 1460, 1160 cm^ー1 (17RS)-20-ethyl-17-methyl-13,1
4-didehydro-PGE 1methyl ester ¹ H-NMR (CDCl₃, 300 MHz) δppm:
0.89 (t, J=7.0Hz, 3H), 0.87~
0.96 (m, 3H), 1.20-1.98 (m, 21
H), 2.20-2.31 (m, 1H), 2.23 (d
d, J=9.4Hz, 18.5Hz, 1H), 2.31
(t, J = 7.5 Hz, 2H), 2.65 (ddd, J
= 1.8Hz, 8.0Hz, 11.1Hz, 1H),
2.75 (ddd, J = 1.4Hz, 7.2Hz, 1
8.5Hz, 1H), 3.67(s, 3H), 4.28
~4.37(m, 1H), 4.47(dt, J = 1.8
Hz, 8.0 Hz, 1H) IR (neat): 3412, 2929, 2858, 2
236, 1742, 1461, 1439, 1168, 1
077,726 cm^ー1 (17S)-2-nor-17,20-dimethyl-13,
14-didehydro-PGE 1methyl ester ¹ H-NMR (CDCl₃, 300 MHz) δppm:
0.90 (t, J = 6.8Hz, 3H), 0.92
(d, J = 6.4 Hz, 3H), 1.13-1.86
(m, 17H), 2.19-2.30 (m, 1H),
2.22(d, J=5.6Hz, 1H), 2.23(d
d, J=9.1Hz, 18.5Hz, 1H), 2.32
(t, J = 7.4 Hz, 2H), 2.54 (d, J =
3.5Hz, 1H), 2.64 (ddd, J = 1.8H
z, 8.3 Hz, 11.3 Hz, 1H), 2.75 (d
dd, J = 1.3Hz, 7.3Hz, 18.5Hz, 1
H), 3.67 (s, 3H), 4.27-4.38
(m, 1H), 4.43-4.54 (m, 1H) IR (neat): 3412, 2930, 2859, 2
237, 1746, 1461, 1439, 1240, 1
166,1077,729 cm^ー1

[0023](17S)-2a-homo-17,20-di
Methyl-13,14-didehydro-PGE1methyle
Stell ¹ H-NMR (CDCl₃, 300 MHz) δppm:
0.84-0.96 (m, 3H), 0.91 (d, J =
6.4 Hz, 3H), 1.10-1.84 (m, 21
H), 2.10-2.35 (m, 1H), 2.23 (d
d, J=9.2Hz, 18.5Hz, 1H), 2.30
(t, J = 7.5 Hz, 2H), 2.65 (ddd, J
= 1.8Hz, 8.3Hz, 11.3Hz, 1H),
2.75 (ddd, J = 1.3 Hz, 7.2 Hz, 1
8.5Hz, 1H), 3.67(s, 3H), 4.27
~4.39(m, 1H), 4.47(dt, J = 1.8
Hz, 7.2Hz, 1H) IR (neat): 3412, 2929, 2857, 2
236, 1746, 1461, 1438, 1167, 1
077cm^ー1 (17R)-17,20-dimethyl-13,14-dide
Hydro-PGE 1allyl ester 1 H-NMR (CDCl₃, 300 MHz) δppm:
0.84-0.98 (m, 3H), 0.93 (d, J =
6.6 Hz, 3H), 1.08-1.84 (m, 19
H), 2.16 (d, J=5.2Hz, 1H), 2.1
9-2.29 (m, 1H), 2.23 (dd, J=9.
2Hz, 18.5Hz, 1H), 2.33 (t, J =
7.5Hz, 2H), 2.64 (ddd, J = 1.7H
z, 8.3Hz, 11.3Hz, 1H), 2.71
(d, J = 3.6 Hz, 1H), 2.75 (ddd, J
= 1.3Hz, 7.2Hz, 18.5Hz, 1H),
4.27-4.38 (m, 1H), 4.42-4.52
(m, 1H), 4.57 (ddd, J=1.4Hz,
1.4Hz, 5.7Hz, 2H), 5.23(ddt,
J=1.4Hz, 1.4Hz, 10.4Hz, 1H),
5.31 (ddt, J = 1.4Hz, 1.4Hz, 1
7.2 Hz, 1 H), 5.92 (ddt, J = 5.7 H
z, 10.4Hz, 17.2Hz, 1H), IR (neat): 3412, 2931, 2859, 2
235, 1741, 1650, 1461, 1382, 1
236, 1163, 1073, 990, 933, 771
cm^-1

Example 2(17S)-17,20-dimethyl-13,14-dide
Hydro-PGE 1 290 mg of the compound obtained in Example 1 (0.735 mmo
l) in 14.5 ml of 50% (v/v) acetone-water
Dissolve and add 130.5 ml of phosphate buffer (10 mM, p
H7.0) and an additional 500 μl (242 units).
(g) porcine liver esterase was added and stirred at room temperature. anti
Follow the reaction by thin-layer chromatography to confirm the disappearance of the raw material.
After confirmation (approximately 15 hours), the reaction mixture was extracted with ethyl acetate.
Drain, wash with saturated brine, dry and concentrate.
The product was subjected to silica gel column chromatography (developing solvent).
solvent; ethyl acetate:methanol=40:1);
115 mg of the title compound were obtained.¹H-NMR (CDCl₃，
300 MHz) δ ppm: 0.80 to 1.00 (m, 6
H), 1.05-1.90 (m, 19H), 2.15-
2.32(m, 2H), 2.30(t, J=7.4H
z, 2H), 2.62 (dd, J = 8.4 Hz, 11 .
3 Hz, 1 H), 2.73 (dd, J = 7.2 Hz, 1
8.4 Hz, 1H), 4.25-4.35 (m, 1
H), 4.45 (dt, J = 1.5 Hz, 7.1 Hz,
1H) IR (neat): 3392, 2931, 2859, 2
238, 1740, 1713, 1463, 1411, 1
380, 1235, 1162, 1077, 758 cm^-1

The following compounds were obtained in the same manner as in Example 2.

[0026](16RS)-16,20-dimethyl-1
3,14,18,18,19,19-hexadehydro-
PGE1 ¹ H-NMR (CDCl₃, 300 MHz) δppm:
0.95-1.17 (m, 6H), 1.18-2.46
(m, 17H), 2.35 (t, J=6.9Hz, 2
H), 2.65 (q, J=9.8Hz, 1H), 2.7
5 (dd, J = 7.3Hz, 18.6Hz, 1H),
4.26-4.40 (m, 1H), 4.43and
4.47 (2d, J = 6.6 Hz and J = 4.1
Hz, 1H) IR (neat): 3400, 2920, 2320, 2
230, 1700, 1680, 1375, 1240, 1
160,1035cm^-1 (17R)-17,20-dimethyl-13,14-dide
Hydro-PGE 1 ¹ H-NMR (CDCl₃, 300 MHz) δppm:
0.85-0.97 (m, 3H), 0.93 (d, J =
6.6 Hz, 3H), 1.10-1.84 (m, 19
H), 2.17-2.30 (m, 1H), 2.24 (d
d, J=9.2Hz, 18.5Hz, 1H), 2.35
(t, J = 7.3 Hz, 1H), 2.65 (ddd, J
= 1.7Hz, 8.3Hz, 11.4Hz, 1H),
2.76 (ddd, J = 1.2 Hz, 7.3 Hz, 1
8.5 Hz, 1 H), 4.27 to 4.37 (m, 1
H), 4.43-4.52 (m, 1H) IR (neat): δppm: 3330, 2930, 2
860, 2240, 1740, 1460, 1380, 1
240, 1160, 1100, 1080, 850cm^-1 17,18,19,20-tetranol-16-cycloheptane
xyl-13,14-didehydro-PGE 1 ¹ H-NMR (CDCl₃, 300 MHz) δppm:
0.81-1.95 (m, 23H), 2.14-2.4
0 (m, 2H), 2.31 (t, J=7.3Hz, 2
H), 2.62 (t, J=9.7Hz, 1H), 2.7
3 (dd, J=7.1Hz, 18.4Hz, 1H),
4.22-4.33 (m, 1H), 4.45 (t, J =
6.8Hz, 1H) IR (neat): 3380, 2920, 2320, 1
735, 1710, 1450, 1150, 1100cm
^ー1

[0027](17RS)-20-nor-17-methyl
-19-(2'-methylprop-1'-enyl)-1
3,14-didehydro-PGE1 ¹ H-NMR (CDCl₃, 300 MHz) δppm:
0.94 (d, J = 6.3Hz, 3H), 1.10~
1.81 (m, 15H), 1.60 (s, 3H), 1.
68 (s, 3H), 1.90-2.04 (m, 2H),
2.18-2.29 (m, 1H), 2.23 (dd, J
= 9.3Hz, 18.4Hz, 1H), 2.34(t,
J = 7.2 Hz, 2H), 2.60-2.69 (m, 1
H), 2.75 (dd, J=7.1Hz, 18.4H
z, 1H), 4.27-4.36 (m, 1H), 4.4
8 (t, J = 6.2 Hz, 1H), 5.09 (t, J =
6.3Hz, 1H) IR (neat): 3350, 2920, 2330, 1
710, 1440, 1380, 1260, 1160, 1
070, 830, 720 cm^-1 (17RS)-20-ethyl-17-methyl-13,1
4-didehydro-PGE 1 ¹ H-NMR (CDCl₃, 300 MHz) δppm:
0.89 (t, J = 7.3 Hz, 3H), 0.91 and
0.93 (d, J=6.6Hz, 3H), 1.10~
1.84 (m, 21H), 2.20-2.32 (m, 1
H), 2.24 (dd, J=9.2Hz, 18.5H
z, 1H), 2.35 (t, J=7.2Hz, 2H),
2.57-2.70 (m, 1H), 2.75 (ddd,
J=1.3Hz, 7.3Hz, 18.5Hz, 1H),
4.27-4.38 (m, 1H), 4.48 (dt, J
= 1.7Hz, 8.0Hz, 1H) IR (neat): 3392, 2929, 2858, 2
240, 1740, 1714, 1463, 1380, 1
240, 1163, 1078, 727 cm^ー1

[0028](17S)-2-nor-17,20-dime
Tyl-13,14-didehydro-PGE1 ¹ H-NMR (CDCl₃, 300 MHz) δppm:
0.85-0.98 (m, 3H), 0.92 (d, J =
6.3Hz, 3H), 1.12-1.89 (m, 17
H), 2.18-2.29 (m, 1H), 2.24 (d
d, J=9.0Hz, 18.4Hz, 1H), 2.36
(t, J = 7.1 Hz, 2H), 2.64 (ddd, J
= 1.6Hz, 8.2Hz, 11.2Hz, 1H),
2.75 (ddd, J = 1.3 Hz, 7.3 Hz, 1
8.4 Hz, 1H), 4.25-4.38 (m, 1
H), 4.49 (dt, J = 1.7 Hz, 7.2 Hz,
1H) IR (neat): 3368, 2930, 2859, 2
237, 1740, 1713, 1462, 1382, 1
235, 1162, 1076, 758, 667 cm^ー1 (17S)-2a-homo-17,20-dimethyl-1
3,14-didehydro-PGE 1 ¹ H-NMR (CDCl₃, 300 MHz) δppm:
0.85-0.96 (m, 3H), 0.91 (d, J =
6.4Hz, 3H), 1.10-1.85 (m, 21
H), 2.18-2.31 (m, 1H), 2.24 (d
d, J=9.1Hz, 18.4Hz, 1H), 2.35
(t, J = 7.3 Hz, 2H), 2.66 (ddd, J
= 1.8Hz, 8.3Hz, 11.3Hz, 1H),
2.76 (ddd, J = 1.3 Hz, 7.2 Hz, 1
8.4 Hz, 1H), 4.27-4.38 (m, 1
H), 4.48 (dt, J = 1.8 Hz, 7.2 Hz,
1H) IR (neat): 3368, 2930, 2858, 2
237, 1741, 1713, 1465, 1411, 1
380, 1235, 1162, 1076, 758, 66
8cm^-1

──────────────────────────────────────────────────── ──── continuation of the front page (72) Inventor Kazuya Kameo Made in Taisho, 3-24-1 Takada, Toshima-ku, Tokyo Yaku Co., Ltd. (72) Inventor Toru Tanami Made in Taisho, 3-24-1 Takada, Toshima-ku, Tokyo Yaku Co., Ltd. (72) Inventor Ken Muto Made in Taisho, 3-24-1 Takada, Toshima-ku, Tokyo Yaku Co., Ltd. (72) Inventor Naoya Ono Made in Taisho, 3-24-1 Takada, Toshima-ku, Tokyo Yaku Co., Ltd. (72) Inventor Jun Goto Made in Taisho, 3-24-1 Takada, Toshima-ku, Tokyo Yaku Co., Ltd.

Claims (1)

[Claims] [Claim 1] Formula (In the formula, R ¹ represents a hydrogen atom, an alkyl group having 1 to 6 carbon atoms or an allyl group, and R ² represents a
branched aliphatic hydrocarbon group, and n is an integer of 4-8. ) and prostaglandin derivatives represented by and salts thereof.