JPH11255740A - 15-deoxy-15-monofluoro-prostaglandin derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject novel compound, having a fluorine atom at the 15-site, and useful as a medicament for treating various diseases, e.g. inflammatory, allergic/immunologic, alimentary, central nervous, and circulatory diseases. SOLUTION: This compound is shown by the formula [A is ethylene, vinylene, ethynylene or the like; R<1> is a 1-8C alkyl, a 3-8C alkenyl or the like; P and Q are each CO, CH(OR<2> ) (R<2> is H or an acyl) or the like; X is CH<2> , O or the like; Z is OR<3> , NHCOR<4> (R<3> and R<4> are each an alkyl, an alkenyl or the like) or the like; and the portion where the solid and broken lines overlap is a single bond, cis double bond or the liked, e.g. 16-phenoxy-15-deoxy-15fluoro-17,18,19,20- tetranol PGE2 . The compound shown by the formula is obtained by protecting the hydroxyl group at the 11-site of a 15-deoxy-15-monofluoro PGE2αderivative, then oxidizing the hydroxyl group at the 9-site and finally releasing the hydroxyl group at the 11-site from protection.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a 15-deoxy-prostaglandin derivative having one fluorine atom at the 15-position.

[0002]

2. Description of the Related Art Natural prostaglandins (hereinafter, prostaglandins are referred to as PG) are a group of physiologically active substances synthesized in vivo, and are used as local hormones having various physiological activities in various tissues of living organisms. Regulates cell function. Among them, in particular, PG which is a kind of natural PG
Class E has vasodilatory action, bronchodilatory action, gastric acid secretion inhibitory action, gastric mucosal protective action, uterine contractile action, and other various actions related to pain and inflammation. It is used as a labor-inducing agent. PGDs also have central nervous system effects, sleep-inducing effects,
It is said to be involved in various actions related to allergy, immune response, and inflammation, in addition to the action of inhibiting platelet aggregation. Therefore, in order to develop these as new pharmaceuticals, the development of PG derivatives with higher effects and no side effects is being studied at home and abroad.

[0003] 15-deoxy-1 which is a derivative in which one fluorine atom is introduced into the 15-position of PG having a natural skeleton.
5-MonofluoroPGs have been reported by Bezglov et al. For example, 15-deoxy-15-monofluoro PGA ₂ , 15-deoxy-15-monofluoro PGB ₂ (Bioorg. Khim. 5 (10),
1531-1536, 1979), 15-deoxy-1
5-monofluoro PGF ₂ α, 15-deoxy-15-
Monofluoro PGE ₂ , 15-deoxy-15-monofluoro PGI ₂ (Dokl. Akad. Nauk SS)
^{SR 2 50 (2), 468-469,1980} ) have been reported in the like.

[0004]

As described above, few reports have been made on 15-deoxy-15-monofluoroPGs having one fluorine atom at the 15-position, and their synthesis examples, physical properties, physiological activities and the like are not so many. unknown. Therefore, it has been strongly desired to synthesize these derivatives and clarify their physical properties and physiological activities.

[0005]

The present invention is the following invention which provides a novel 15-deoxy-15-monofluoroPG derivative having one fluorine atom at the 15-position. That is, the present invention relates to 15-deoxy-15-monofluoro-
PGE derivative, 15-deoxy-15-monofluoro-PGD derivative, 15-deoxy-15-monofluoro-PGI derivative, 15-deoxy-15-monofluoro-PGA derivative, 15-deoxy-15-mono Derivatives of fluoro-PGB, and 15-deoxy-15
A 15-deoxy-15-monofluoro-PG derivative selected from derivatives of monofluoro-PGJ, or a salt thereof (provided that one of PG having a natural skeleton is provided)
Natural type 1, which is a derivative with one fluorine atom introduced at the 5-position
Except for 5-deoxy-15-monofluoroPGs and salts thereof. ).

The present invention also relates to derivatives of 15-deoxy-15-monofluoro-PGE and 15-deoxy-1
15- selected from derivatives of 5-monofluoro-PGD
Provide a deoxy-15-monofluoro-PG derivative or a salt thereof (provided that natural 15-deoxy-15-monofluoro is a derivative in which one fluorine atom is introduced at the 15-position of PG having a natural skeleton. PGEs and salts thereof, and natural 15-deoxy-15-monofluoro-PGDs and salts thereof are excluded).

Further, the present invention provides a 15-deoxy-15-monofluoro-PG derivative represented by the following general formula (1), or a salt thereof.

[0008]

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(However, the symbols in the general formula (1) have the following meanings.)

A: ethylene group, vinylene group, ethynylene group, —OCH ₂ —, or —SCH ₂ —.

R ¹ : alkyl group having 1 to 8 carbon atoms, substituted alkyl group having 1 to 8 carbon atoms, alkenyl group having 3 to 8 carbon atoms, substituted alkenyl group having 3 to 8 carbon atoms, carbon number 3-8 alkynyl group, substituted alkynyl group having 3-8 carbon atoms, cycloalkyl group having 3-8 carbon atoms, substituted cycloalkyl group having 3-8 carbon atoms, aralkyl group, substituted alkynyl group An alkyl group, an aryloxyalkyl group, or a substituted aryloxyalkyl group;

P and Q: each independently -CO-, -C
H (OR ² ) — or —CH ₂ —. However the P and Q, is not a -CH (OR ²⁾ simultaneously -CO- or simultaneously (wherein R ² each independently represent a hydrogen atom or an acyl group. Further, one and Z of R ² jointly To form a single bond.)

X: -CH _2- , -O-, or -S-.

Z: -OR ³ , -NHCOR ⁴ , -NHS
O ₂ R ⁵ , —SR ⁶ , or —NR ⁷ R ⁸ . Further, one of Z and R ² may form a single bond together (provided that R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸
Are each independently a hydrogen atom, an alkyl group, a substituted alkyl group, an alkenyl group, a substituted alkenyl group, an alkynyl group, a substituted alkynyl group, a cycloalkyl group, a substituted cycloalkyl group, an aryl group, a substituted aryl group, an aralkyl group, Shows a substituted aralkyl group. ).

The overlap between the solid and broken lines: a single bond, a cis double bond, or a trans double bond.

Wherein A is an ethylene group, P is -CO-,
Q is -CH (OH) -, X is -CH ₂ -, Z is OH, R
¹ is an n-pentyl group, and an overlapped portion between a dotted line and a broken line is a cis double bond, and A is an ethylene group, and P is -CH
(OH) -, Q is -CO-, X is -CH ₂ -, Z is O
Excludes the case where H and R ¹ are n-pentyl groups and the overlap between the dotted line and the broken line is a cis double bond. )

[0017]

DESCRIPTION OF THE PREFERRED EMBODIMENTS In the following description of the present specification,
When the organic group is “lower”, it means 1 to 6 carbon atoms. Preferred lower organic groups are organic groups having 1 to 4 carbon atoms.
The “alkyl group” may be linear or branched, and a lower alkyl group is preferred unless otherwise specified.
Suitable examples include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, pentyl, hexyl and the like.

The "alkenyl group" is preferably a lower alkenyl group unless otherwise specified, more preferably a straight-chain or branched alkenyl group having 2 to 6 carbon atoms and one unsaturated group. Examples include vinyl, allyl, 1-propenyl, isopropenyl,
Examples thereof include a 3-butenyl group, a 3-pentenyl group, and a 4-hexenyl group.

The "alkynyl group" is preferably a lower alkynyl group unless otherwise specified, more preferably a straight-chain or branched alkynyl group having 2 to 6 carbon atoms and one unsaturated group. Examples include 1-propynyl, 2-propynyl, 3-butynyl, 3-pentynyl, 4-hexynyl and the like.

As the "alkoxy group", a wide range of general alkoxy groups is used, but a lower alkoxy group is preferable, and a linear or branched alkoxy group having 1 to 4 carbon atoms is more preferable. Examples include methoxy, ethoxy, propoxy, butoxy and the like.

"Halogen atom" means a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. “Aryl group” refers to a monovalent aromatic hydrocarbon group, and a substituent (for example,
A lower alkyl group, a halogen atom, a halogenated alkyl group, a lower alkoxy group, a lower alkylamino group, etc.), and preferably a phenyl group or a derivative thereof, for example, a phenyl group, a tolyl group, a halophenyl group ( For example, chlorophenyl, fluorophenyl,
Bromophenyl group, etc., dihalophenyl group (eg, dichlorophenyl group, difluorophenyl group, dibromophenyl group, etc.), trihalophenyl group (eg, trichlorophenyl group, trifluorophenyl group, tribromophenyl group, etc.), alkyl halide-substituted phenyl group (Eg, trifluoromethylphenyl group), alkoxyphenyl group (eg, methoxyphenyl group, ethoxyphenyl group, etc.), dialkoxyphenyl group (eg, dimethoxyphenyl group, diethoxyphenyl group, etc.), trialkoxyphenyl group (eg, trimethoxyphenyl group). Phenyl group, triethoxyphenyl group, etc.).

The "aralkyl group" refers to an aryl group-substituted alkyl group, and examples of the aryl group as the substituent include those described above. The alkyl group has 1 to 4 carbon atoms.
Is preferred. Suitable examples include benzyl, benzhydryl, trityl, phenethyl and the like.

The term "cycloalkyl group" refers to an unsubstituted or substituted 3- to 8-membered cycloalkyl group. When substituted, examples of the substituent include a lower alkyl group, a halogen atom, and an alkoxy group. Examples thereof include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, a methylcyclohexyl group, a dimethylcyclopentyl group, a dimethylcyclohexyl group, a chlorocyclohexyl group, and a dichlorocyclohexyl group.

"Halogenated alkyl group" refers to a lower halogenated alkyl group halogenated with one or more halogen atoms. Fluoromethyl, difluoromethyl, trifluoromethyl, trifluoroethyl, pentafluoroethyl, chloromethyl, dichloromethyl, trichloromethyl, bromomethyl and the like.

The term "acyl group" refers to a monovalent or polyvalent group formed by removing a hydroxyl group from all carboxyl groups of a carboxylic acid. The carboxylic acids include saturated or unsaturated aliphatic carboxylic acids, carbocyclic carboxylic acids, and heterocyclic carboxylic acids. Carbocyclic carboxylic acids include saturated or unsaturated cyclic aliphatic carboxylic acids and aromatic carboxylic acids.

As the 15-deoxy-15-monofluoro PG derivative of the present invention, a derivative in which one fluorine atom is introduced at the 15-position of PG is replaced with one fluorine atom at the 15-position of PG having a natural skeleton. 15-deoxy-15-monofluoro-PGE
Of 15-deoxy-15-monofluoro-PG
Derivative of D, 15-deoxy-15-monofluoro-P
GI derivative, 15-deoxy-15-monofluoro-
A derivative of PGA, a derivative of 15-deoxy-15-monofluoro-PGB, or a derivative of 15-deoxy-15-monofluoro-PGJ.

Of these, 15-deoxy- of the present invention
As the 15-monofluoro PG derivative, a derivative of 15-deoxy-15-monofluoro-PGE or
-Deoxy-15-monofluoro-PGD derivative (however, natural 15-deoxy-1 which is a derivative in which one fluorine atom is introduced into position 15 of PG having a natural skeleton)
Excludes 5-monofluoro PGEs and salts thereof, and natural 15-deoxy-15-monofluoro-PGDs and salts thereof. ) Is preferable, and particularly, the general formula (1)
15-deoxy-15-monofluoro-PG represented by
Derivatives, or salts thereof, are preferred.

15-deoxy- represented by the general formula (1)
As the 15-monofluoro PG derivative (hereinafter, also referred to as 15-deoxy-15-monofluoro PG derivative (1)), the following compounds are preferable from the viewpoint of physiological activity and physical properties. A in the general formula (1) is preferably a vinylene group or an ethylene group, and the vinylene group includes cis and trans vinylene groups. Particularly, a vinylene group of trans is preferable. A represents -OCH ₂ -or -SCH
_When it is _2-, it is preferable that the bond is made to the ring with an oxygen atom or a sulfur atom. The X -CH ₂ - it is particularly preferred. The overlap between the solid line and the broken line in the general formula (1) is most preferably a cis double bond.

R ¹ is an alkyl group having 1 to 8 carbon atoms, a substituted alkyl group having 1 to 8 carbon atoms,
An alkenyl group having 8 carbon atoms, a substituted alkenyl group having 3 to 8 carbon atoms, an alkynyl group having 3 to 8 carbon atoms, a substituted alkynyl group having 3 to 8 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, A cycloalkyl group having 3 to 8 carbon atoms, an aralkyl group, a substituted aralkyl group, an aryloxyalkyl group, or a substituted aryloxyalkyl group, which is an ω chain portion of a natural PG. (However, when this group is adopted, the structure other than R ¹ is unnatural) or various unnatural PGs
Group corresponding to the omega chain portion of the class.

When R ¹ is a substituted alkyl group,
Examples of the substituent include organic groups having a ring such as a cycloalkyl group, and examples of the substituent in the substituted alkenyl group and the substituted alkynyl group include organic groups having a ring such as an aryl group and a cycloalkyl group. Can be Examples of such R ¹ include a cycloalkyl-substituted alkyl group, a cycloalkyl-substituted alkenyl group, and an aryl-substituted alkenyl group.

When R ¹ is a substituted alkyl group, one or more of the carbon atoms of the alkyl group may be substituted with an etheric oxygen atom or a thioetheric sulfur atom. A divalent ring group such as a cycloalkylene group or an arylene group may be inserted between carbon atoms.

When R ¹ is a substituted cycloalkyl group having 3 to 8 carbon atoms, a substituted aralkyl group or a substituted aryloxyalkyl group, the substituent may be a halogen atom, an oxygen atom-containing group, A sulfur atom group, a nitrogen atom-containing group and an alkyl group are preferred, and an alkyl group is particularly preferred. Further, the substituent is preferably bonded to a ring group.

In the formula 1, R ¹ is an alkyl group having 1 to 8 carbon atoms, a substituted alkyl group having 1 to 8 carbon atoms,
8 alkenyl group, a substituted alkenyl group having 3 to 8 carbon atoms, an alkynyl group having 3 to 8 carbon atoms, or a substituted alkynyl group having 3 to 8 carbon atoms (hereinafter collectively referred to as a chain hydrocarbon group) ), It has 5 to 6 carbon atoms.
Is preferably a linear alkyl group, an alkenyl group, or an alkynyl group, or a group in which one or two methyl groups are substituted on these groups.

When R ¹ is a chain hydrocarbon group, specific examples include n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-decyl group, 1-methylpentyl group, 1,1-dimethylpentyl group, 1-methylhexyl group, 2-methylpentyl group, 2-methylhexyl group, 3-pentenyl group, 1-methyl-3-pentenyl group , 1-methyl-3-
Hexenyl group, 1,1-dimethyl-3-pentenyl group,
1,1-dimethyl-3-hexenyl group, 2-methyl-3
-Pentenyl group, 2-methyl-3-hexenyl group, 3-
Pentynyl group, 1-methyl-3-pentynyl group, 1-methyl-3-hexynyl group, 2-methyl-3-pentynyl group, 2-methyl-3-hexynyl group, 1,1-dimethyl-3-pentynyl group, 1,1-dimethyl-3-hexynyl group is preferred, and n-pentyl group, 2-methylhexyl group, 1-methyl-3-pentynyl group, 1-methyl-3-
A hexynyl group and a 1,1-dimethyl-3-hexynyl group are particularly preferred.

When R ¹ is a substituted alkyl group having 1 to 8 carbon atoms, another example is an alkyl group having 1 to 8 carbon atoms substituted with a cycloalkyl group. Preferred is an alkyl group having 1 to 4 carbon atoms. The cycloalkyl group in the group is preferably a cyclopentyl group or a cyclohexyl group, and the alkyl group in the group is preferably an alkyl group having 1 to 2 carbon atoms.

Preferred examples of the case where R ¹ is an alkyl group having 1 to 8 carbon atoms substituted with a cycloalkyl group include a cyclopentylmethyl group, a 2-cyclopentylethyl group, a cyclohexylmethyl group and the like.

When R ¹ is a cycloalkyl group having 3 to 8 carbon atoms or a substituted cycloalkyl group having 3 to 8 carbon atoms, it is substituted by one or more lower alkyl groups of hydrogen atoms of the cycloalkyl group. Or a cycloalkyl group having 3 to 8 carbon atoms, particularly a cyclopentyl group,
A cyclohexyl group, a cyclopentyl group substituted with an alkyl group having 1 to 4 carbon atoms, and a cyclohexyl group substituted with an alkyl group having 1 to 4 carbon atoms are preferable.

[0038] When R ¹ is an aralkyl group or a substituted aralkyl group, the R ^1, aralkyl group, or one or more halogen atoms of the hydrogen atoms of the aralkyl group, a halogenated alkyl group, an alkoxy A group or a group substituted by a hydroxyl group is preferred. As the aralkyl group, a group containing a benzene ring, a furan ring, a thiophene ring, or a naphthalene ring is preferable. The alkyl portion of the aralkyl group (that is, the alkylene group) has 1 to 1 carbon atoms.
4 is preferred. Preferred examples of the aralkyl group or the substituted aralkyl group include a phenyl group-containing alkyl group having 1 to 2 carbon atoms, or a methyl group, an ethyl group,
Or an alkyl group having 1 to 2 carbon atoms having a phenyl group to which a halogen atom is bonded.

When R ¹ is an aralkyl group or a substituted aralkyl group, preferred examples include a phenylmethyl group, a 2-phenylethyl group, a 3-methylphenylmethyl group and a 2- (3-methylphenyl) Ethyl group, 3
-Trifluoromethylphenylmethyl group, 2- (3-trifluoromethylphenyl) ethyl group, 3-chlorophenylmethyl group, 2- (3-chlorophenyl) ethyl group,
2- (3,5-dichlorophenyl) ethyl group, 2-
And a (3,4-dichlorophenyl) ethyl group.

When R ¹ is an aryloxyalkyl group or a substituted aryloxyalkyl group, an aryloxyalkyl group containing a benzene ring, a furan ring, a thiophene ring, a naphthalene ring, or the like; A group substituted with an atom, a halogenated alkyl group, an alkoxy group, a hydroxyl group, or the like is preferable. Further, the aryl moiety of the aryloxyalkyl group preferably has a phenyl group or one to three halogen atoms or halogenated alkyl groups bonded to the phenyl group. The number of carbon atoms in the alkyl group portion of the aryloxyalkyl group is preferably 1 to 3.

When R ¹ is an aryloxyalkyl group or a substituted aryloxyalkyl group, preferred examples include a phenoxymethyl group, a 3-chlorophenoxymethyl group, a 3-fluorophenoxymethyl group,
Trifluoromethylphenoxymethyl group, 3,5-dichlorophenoxymethyl group, 3,4-dichlorophenoxymethyl group, 3,5-difluorophenoxymethyl group,
3,4-difluorophenoxymethyl group, 3,5-bis (trifluoromethyl) phenoxymethyl group, 3,4-
And a bis (trifluoromethyl) phenoxymethyl group.

R ¹ in the formula (1) is preferably an aryloxyalkyl group or a substituted aryloxyalkyl group, particularly preferably a phenoxymethyl group or a substituted phenoxymethyl group. -Chlorophenoxymethyl group, 3,5-
A dichlorophenoxymethyl group or a 3,4-dichloro group is preferred.

[0043] Equation (1) in, -A-CFH-R ¹ moiety, since the the structure of the non-natural form is preferred, when A is a vinylene group and R ¹ is an n- pentyl Other structures are particularly preferable, especially when A is a vinylene group and R ¹ is a lower alkyl group.

R ² is each independently a hydrogen atom or an acyl group. In addition, one of R ² and Z may form a single bond together. When R ² is an acyl group, the compound of formula (1) is particularly useful as a prodrug because it can be converted into a biologically active compound by hydrolysis in vivo. As the acyl group, an acyl group having 2 to 20 carbon atoms is preferable, and an acyl group having a carbonyl group bonded to a terminal of a monovalent aliphatic hydrocarbon group having 2 to 20 carbon atoms is particularly preferable. As the monovalent aliphatic hydrocarbon group, a linear monovalent aliphatic hydrocarbon group having 4 or more carbon atoms is preferable.
When R ² is an acyl group in which a carbonyl group is bonded to the terminal of a linear monovalent aliphatic hydrocarbon group having 4 or more carbon atoms, the compound of the formula (1) is useful as a prodrug having improved lipophilicity. It is.

Z is -OR ³ , -NHCOR ⁴ , -NH
SO ₂ R ⁵ , —SR ⁶ , or —NR ⁷ R ⁸ . Further, one of R ² and Z may form a single bond together. Examples of the case where one of R ² and Z together form a single bond include when Z is OH and P or Q is -C
A compound of the formula (1) wherein H (OH)-is a carboxyl group at the α-chain terminal and a hydroxyl group at the 9- or 11-position
Is a divalent linking group formed when an α-chain terminal carboxyl group and a hydroxyl group of the compound of the formula (1) are subjected to an esterification reaction. Is mentioned. The compound having a ring formed by the ester bond can be converted into a physiologically active compound by hydrolysis in a living body, and thus is useful as a prodrug.

R ^{3 to} R ⁸ each independently represent a hydrogen atom, an alkyl group, a substituted alkyl group, an alkenyl group, a substituted alkenyl group, an alkynyl group, a substituted alkynyl group, a cycloalkyl group, a substituted cycloalkyl group, an aryl group, It represents a substituted aryl group, an aralkyl group, or a substituted aralkyl group.

R ^{3 to} R ⁸ are an alkyl group, a substituted alkyl group, an alkenyl group, a substituted alkenyl group, an alkynyl group,
When it is a substituted alkynyl group, these groups may be linear or branched. Specific examples of the substituent in these groups include the same examples as R ^1, and a halogen atom or a cycloalkyl group is preferable.

When R ^{3 to} R ⁸ are each a halogen atom-substituted alkyl group or a cycloalkyl group-substituted alkyl group, the halogen atom-substituted alkyl group preferably has 6 or less carbon atoms. The group portion preferably has 1 to 2 carbon atoms, and specific examples of the cycloalkyl group portion include the following examples. Examples of the halogen-substituted alkyl group include a trifluoromethyl group and a pentafluoroethyl group.
Examples of the cycloalkyl-substituted alkyl group include a cyclobutylmethyl group, a cyclopentylmethyl group, and a cyclohexylmethyl group.

R ^{3 to} R ⁸ are an alkyl group, a substituted alkyl group, an alkenyl group, a substituted alkenyl group, an alkynyl group,
When it is a substituted alkynyl group, each has 1 to 2 carbon atoms.
It is preferably 0, and particularly preferably 1 to 8. Specific examples of these groups include the following groups. Examples of the alkyl group (R ^{3 to} R ⁸ ) include a methyl group, an ethyl group, n
-Propyl, isopropyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-decyl, 1-methylpentyl, 1,1
-Dimethylpentyl, 1-methylhexyl, 2-methylpentyl, 2-methylhexyl and the like.

The alkenyl group (R ^{3 to} R ⁸ ) includes allyl, 2-butenyl, 3-pentenyl, 1-methyl-3-pentenyl, 1-methyl-3-hexenyl, 1,1- Dimethyl-3-pentenyl group, 1,1-dimethyl-3-hexenyl group and the like. Examples of the alkynyl group or substituted alkynyl group (R ^{3 to} R ⁸ ) include a propargyl group, a 3-pentynyl group, a 1-methyl-3-pentynyl group, a 1-methyl-3-hexynyl group, and a 1,1-dimethyl-3- group. Pentynyl group, 1,1-dimethyl-3-hexynyl group and the like.

When R ^{3 to} R ⁸ are a cycloalkyl group, a substituted cycloalkyl group, an aryl group, a substituted aryl group, an aralkyl group, or a substituted aralkyl group, specific examples are the same as those described for R ^1. Is mentioned. When these groups have a substituent, the substituent is preferably an alkyl group.

The cycloalkyl group or substituted cycloalkyl group (R ^{3 to} R ⁸ ) preferably has 3 to 10 carbon atoms. Specific examples include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a 2,2-dimethylcyclopropyl group, a 3-cyclopenten-1-yl group, a 3-cyclohexen-1-yl group, and a cyclooctyl group. Can be An aryl group or a substituted aryl group (R ^{3 to} R
⁸ ) is preferably a phenyl group or a substituted phenyl group. As the substituent, an alkyl group (preferably having 4 or less carbon atoms), a halogenated methyl group, a halogen atom, an alkoxy group, an acyl group, an acylamino group, a nitro group, and the like are preferable. An aryl group or a substituted aryl group (R ^{3 to} R
Specific examples of ⁸ ) include a phenyl group, a 4-methylphenyl group, a 4- (t-butyl) phenyl group, a 3-trifluoromethylphenyl group, a 4-trifluoromethylphenyl group, a 4-chlorophenyl group, and a 4-chlorophenyl group. Acetylphenyl group,
Examples thereof include a 4-benzoylphenyl group, a 4-acetylaminophenyl group, a 4-benzoylaminophenyl group, a 3-nitrophenyl group, and a 4-nitrophenyl group.

The aralkyl group or substituted aralkyl group (R ^{3 to} R ⁸ ) includes a phenyl group having 4 carbon atoms.
Aralkyl groups comprising the following (preferably 1 or 2 carbon atoms) alkyl groups are preferred. The alkyl group portion may have a branch. Further, an alkyl group (preferably having 4 or less carbon atoms), a halogenated methyl group, a halogen atom, an alkoxy group, an acyl group, an acylamino group, a nitro group, and the like may be bonded to the phenyl group.

Specific examples of the aralkyl group or the substituted aralkyl group (R ^{3 to} R ⁸ ) include a benzyl group, a phenethyl group, a benzhydryl group, a 3-methylphenylmethyl group, a 3-chlorophenylmethyl group and a 3-fluorophenyl Methyl group, 3-bromophenylmethyl group, 3-trifluoromethylphenylmethyl group, 1- (3-methylphenyl) ethyl group, 1- (3-chlorophenyl) ethyl group, 1- (3-trifluoromethylphenyl) Ethyl group, 1- (3-fluorophenyl) ethyl group, 1- (3
-Bromophenyl) ethyl group, 2- (3-methylphenyl) ethyl group, 2- (3-chlorophenyl) ethyl group,
2- (3-trifluoromethylphenyl) ethyl group, 2
-(3-fluorophenyl) ethyl group, 2- (3-bromophenyl) ethyl group, 1-methyl-2- (3-methylphenyl) ethyl group, 1-methyl-2- (3-chlorophenyl) ethyl group, 1-methyl-2- (3-trifluoromethylphenyl) ethyl group, 1-methyl-2- (3-
Fluorophenyl) ethyl group, 1-methyl-2- (3-
(Bromophenyl) ethyl group and the like.

As R ^{3 to} R ⁸ , an alkyl group, a substituted alkyl group, a cycloalkyl group, a substituted cycloalkyl group, an aralkyl group, or a substituted aralkyl group, each of which may have a substituent. preferable. As the substituent in these groups, a halogen atom or an alkyl group having 1 to 4 carbon atoms bonded to a ring is preferable.

Further, R ^{3 to} R ⁸ are preferably an alkyl group, and particularly preferably, R ⁵ is an alkyl group substituted with a halogen atom.

Z in the formula (1) is preferably -OR ³ , and particularly, R ³ is a hydrogen atom, an alkyl group having 1 to 20 carbon atoms, a cycloalkyl group having 3 to 20 carbon atoms, and 1 carbon atom. ~
—OR ³ when it is a 20 aralkyl group is preferred.
Compound Z is -OR ³ (except when R ³ is a hydrogen atom), are useful as prodrugs because it can be converted to compounds with a hydrolyzed bioactive in vivo. In addition, the type of R ³ can be selected to improve the fat solubility. Further, Z in the formula (1) is a hydroxyl group, a methoxy group, an ethoxy group, an isopropoxy group, an isobutoxy group,
It is preferably a cyclohexyloxy group or a benzyloxy group.

However, from the compound of the formula (1) of the present invention,
A is an ethylene group, P is -CO-, Q is -CH (OH)
-, X is -CH ₂ -, Z is OH, R ¹ is n- pentyl group and a compound dotted and dashed overlapping portion is cis double bond, and, A is an ethylene group, P is -CH ( OH)
-, Q is -CO-, X is -CH ₂ -, Z is OH, R ¹ is n- pentyl group and a compound dotted and dashed overlapping portion is cis double bond, is excluded.

When the 15-deoxy-15-monofluoro PG derivative of the present invention has an acidic group such as a carboxyl group (for example, when Z is a hydroxyl group), it may be a salt with a base. Similarly, when it has a basic group such as an amino group, it may be a salt with an acid. As salts with bases, alkali metal salts such as sodium salts and potassium salts,
Examples thereof include alkaline earth metal salts such as calcium salts and magnesium salts, and ammonium salts such as unsubstituted ammonium salts and alkyl-substituted ammonium salts. Examples of the salt with an acid include inorganic acid salts such as hydrochloride, sulfate and phosphate, and organic acid salts such as acetate, oxalate, citrate, succinate and p-toluenesulfonate. No.

Next, the 15-deoxy-15- according to the present invention.
The monofluoro PG derivative will be described. Among the 15-deoxy-15-monofluoro PG derivatives, those having a carbon skeleton similar to the natural type can be synthesized by the same method as general PGs. Further, those having a special PG skeleton such as a carbacycline skeleton, an isocarbacycline skeleton, a benzoprostacyclin skeleton, and an interphenylene skeleton can be synthesized by synthesizing each 15-alcohol derivative and then fluorinating.

For example, 15-deoxy-15-monofluoro PGF ₂ α having a structure similar to a natural PG skeleton
The derivative can be synthesized by the following method. That is, using Corey lactone as a starting material, ketones obtained by introducing an ω chain are first selectively reduced to alcohol, and a fluorination reaction is carried out.
Into a corey lactone with an ω chain. Next, the corey lactone with the ω chain is reduced to lactols, and then an α chain is introduced by a Wittig reaction, and deprotection or acylation of a hydroxyl group is performed as required.
Furthermore, the carboxyl group moiety desired ester, acylamide, sulfonamide, by converting like thioester or amide, 15-deoxy-15-mono-fluoro PGF ₂ alpha derivative (2) is obtained. However, the symbols in the formula (2) have the same meaning as described above.

[0062]

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[0063] Further 15-deoxy-15-mono-fluoro PGF ₂ alpha derivative (2) as a raw material, various 15
Deoxy-15-monofluoro PG derivative (1a-1
f) can be synthesized. However, the symbols in the formulas (1a) to (1f) have the same meaning as described above.

[0064]

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For example, the 15-deoxy-15-monofluoro PGE derivative (1a) is
- oxidizing the 9 position of the hydroxyl group After protecting the 11-position hydroxyl group of the mono-fluoro PGF ₂ alpha derivative (2) can be synthesized by deprotecting the 11-position. Further, after protecting the hydroxyl group at the 11-position of the corey lactone with the ω chain, it is converted into lactol, and an α chain is introduced by a Wittig reaction,
It can also be synthesized by oxidizing the hydroxyl group at the 9-position and deprotecting the 11-position.

15-deoxy-15-monofluoroPG
D derivative (1b), after protected the 9-position of 15-deoxy-15-mono-fluoro PGF ₂ alpha derivative (2) 11
It can be synthesized by oxidizing the position and deprotecting the 9 position. Fifteen
-Deoxy-15-monofluoro PGI derivative (1c)
Is 15-deoxy-15-mono-fluoro PGF ₂ alpha derivative (2), reacting cyclized with iodine or N- iodosuccinimide, it can be synthesized by hydrogenation reaction de iodide. The 15-deoxy-15-monofluoro PGA derivative (1d) and the 15-deoxy-15-monofluoro PGB derivative (1e) can be prepared in the presence of an acid, a base, and other dehydrating agents. PGE
The derivative (1a) can be synthesized by a dehydration reaction. Similarly, the 15-deoxy-15-monofluoro PGJ derivative (1f) is a 15-deoxy-15-monofluoro PGJ derivative.
It can be synthesized by subjecting the D derivative (1b) to a dehydration reaction.

15-Deoxy-15-monofluoroPG
The synthesis of the F ₂ α derivative (2) is described in Japanese Patent Application No. 8-3 of the inventors.
46286 can be used. For example, alcohols (4) obtained by reducing various ketones (3) with an ω chain are subjected to a fluorination reaction to produce corey lactones (5) having an ω chain having one fluorine atom at the 15-position. Then, the lactone (5) is reduced to convert it into a lactol (6), and the lactol (6) is reacted with a phosphorane (7) to introduce an α-chain unit. Deoxy-15-monofluoro P
The GF ₂ α derivative (2) is obtained. Phosphoranes (7)
Is obtained from phosphonium salts (8).

15-deoxy-15-monofluoroPG
The derivatives (1a to 1f) are each 15-deoxy-1
It can be synthesized from 5-monofluoro PGF ₂ α derivative (2). The starting compound does not necessarily have to have the same configuration as the 15-deoxy-15-monofluoroPG derivative (1a-1f). Therefore, the configuration of the substituent bonded to the cyclopentane ring in the following general formulas (2) to (7) is not specified. In addition, the following general formula (7),
In (8), R ⁹ is an alkyl group, a substituted alkyl group,
It represents an aryl group, a substituted aryl group, an aralkyl group, a substituted aralkyl group or a dialkylamino group, and Y represents a halogen atom such as a chlorine atom, a bromine atom and an iodine atom. However, the symbols in the following formula have the same meaning as described above.

[0069]

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Except when R ¹ is a specific substituent, the above ketones are known compounds. Ketones when R ¹ is a specific substituent can be produced in the same manner as known ketones. For example, α, β-unsaturated ketones can be produced by reacting a dialkyl 3-substituted-2-oxopropylphosphonate with a corelylactone having a formyl group. The α, β-unsaturated ketones are stereoselectively reduced using a selective reducing agent, and a selective reducing agent is used in the production of allyl alcohols. Can be applied.

Regarding the selective reducing agent, "New Experimental Chemistry Lecture 15 Oxidation and Reduction (II) (Maruzen),""Fourth Edition Experimental Chemistry Lecture 26 Organic Synthesis VIII" (Maruzen), "Houben-W"
eyl, Method of Organic Chemistry-E21
d. Stereoselective synthesis "(G. Heim
For example, a selective reducing agent described in, for example, Chen et al., Thieme Stuttgart) may be employed, and the selective reducing agent may include a hydrogenation catalyst, a hydrosilylation reagent, a hydride reducing agent, and the like.

Specific examples of the selective reducing agent include hydrogenation catalysts such as rhodium, ruthenium and platinum, hydrosilylation catalysts, metal hydrides containing metals such as aluminum, boron, tin and silicon, and aluminum hydride complex compounds. ,
Examples thereof include metal hydride complex compounds such as borohydride complex compounds, metal-containing alkoxides or metal-containing alkylated compounds such as aluminum, magnesium, zinc, potassium, and boron, and combinations of these with Lewis acids. Examples of the metal ligand include amines, alcohols, phosphines and the like, and optically active substances thereof. Specific examples of the metal ligand include diisobutylaluminum hydride, diborane, disiamylborane, texylborane, 9
-Borabicyclo [3.3.1] nonane, tributyltin hydride, triethylsilane, trichlorosilane, lithium aluminum hydride, lithium trialkoxyaluminum hydride, bis (2-methoxyethoxy) hydride
Sodium aluminum, sodium borohydride, sodium trimethoxy borohydride, zinc borohydride, lithium tri-s-butyl borohydride (L-selectride), potassium tri-s-butyl hydride (K-
Selectride), lithium triamylborohydride (KL-selectride), lithium triethylborohydride (superhydride), alpine hydride, dialkylaluminum alkoxide, alpine borane, diisopinocan phenyl chloroborane, and the like. Isopinocan phenylchloroborane is preferred.

The amount of the reducing agent to be used is generally 1 to 50 equivalents, preferably 1 to 20 equivalents, based on the α, β-unsaturated ketone. The reaction temperature is preferably about -150 to + 100C, particularly preferably -80 to 0C. The above-mentioned selective reduction reaction can be usually carried out in the presence of a solvent. As a reaction solvent, toluene, hexane, benzene, pentane, xylene, petroleum ether, and the like, and as an ether solvent, diethyl ether, tetrahydrofuran, 1,4-dioxane, dimethoxyethane, diglyme, t-butyl methyl ether, and the like are used. Particularly, tetrahydrofuran is preferred.

When synthesizing saturated alcohols (that is, A is an ethylene group) as the alcohol (4), hydrogenate allyl alcohols or hydrogenate α, β-unsaturated ketones and then select them. Can be synthesized by reduction. Various known reactions can be used for the hydrogenation reaction. For example, "New Experimental Chemistry Course 15 Oxidation and Reduction (II)" (Maruzen), "4th Edition Experimental Chemistry Course 26"
Methods described in Organic Synthesis VIII, Asymmetric Synthesis, Reduction, Sugar, Labeling Compounds (Maruzen) and the like can be used.

A catalyst is usually used for the hydrogenation reaction. As the catalyst, platinum, palladium, rhodium, ruthenium, iridium, cobalt, chromium oxide, copper, osmium, molybdenum, Raney nickel, Raney cobalt, platinum oxide, platinum-silica gel, palladium-carbon, palladium-silica gel, palladium-barium sulfate, Examples thereof include copper chromite, nickel boride, chromium-zinc oxide, copper-barium-chromium oxide, and chlorotriphenylphosphine rhodium. Raney nickel, platinum oxide, and palladium-carbon are preferably used.

A solvent may be used for the hydrogenation reaction.
As the solvent, water, alcohol, ethyl acetate, acetic acid, ether, benzene, hexane, dioxane, toluene,
Dichloromethane is preferred, and alcohol, ethyl acetate and the like are particularly preferred.

The hydrogenation reaction may be performed in the presence of a base or an acid. Examples of bases or acids include sulfuric acid, hydrochloric acid, perchloric acid, phosphoric acid, acetic acid, oxalic acid, trifluoroacetic acid, activated carbon, alumina, sodium hydroxide, potassium hydroxide, triethylamine, diisopropylethylamine, pyridine, 2,6 -Lutidine, dimethylaminopyridine, barium sulfate, calcium carbonate, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium nitrite, potassium nitrite and the like.

The hydrogen pressure in the hydrogenation reaction is usually 1 to 100 atm, preferably 1 to 10 atm. Further, the reaction temperature is preferably about -150 to + 100 ° C,
Particularly, -20 to 50C is preferable.

The alcohol is subjected to a fluorination reaction to give 15
Various known fluorination methods can be applied to convert to a ω-chain-containing coreylactone having one fluorine atom at the position. For example, a method of reacting in an inert solvent using various nucleophilic fluorinating agents is employed. When the alcohols have a functional group that may be fluorinated during the fluorination reaction, it is preferable to protect the functional group with a protecting group in advance. For example, when R ² is a hydrogen atom, it is preferable to protect with a protecting group, fluorinate the hydroxyl group at the 15-position, and then perform deprotection.

As the protecting group, a triorganosilyl group,
Examples include an acyl group, an alkyl group, an aralkyl group, and a cyclic ether group. In addition, 1 in the raw material alcohols
The hydroxyl group at position 1 is protected with an acyl group, and the desired 15-
When R ^{2 of the} deoxy-15-difluoro PG derivative (1) is also an acyl group, it may be the same as or different from R ^2. After protection, an acyl group corresponding to R ² may be introduced.

A triorganosilyl group as a protecting group is
A group in which three organic groups such as an alkyl group, an aryl group, an aralkyl group, and an alkoxy group are bonded to a silicon atom. Particularly, a group selected from a lower alkyl group and an aryl group
A triorganosilyl group having one is preferred. Specifically, for example, a t-butyldimethylsilyl group, a t-butyldiphenylsilyl group, a triethylsilyl group, a triphenylsilyl group, a triisopropylsilyl group and the like are preferable.

As the acyl group, an acetyl group, a trifluoroacetyl group, a pivaloyl group, a benzoyl group, a p-phenylbenzoyl group and the like are preferable, and as the cyclic ether group, a tetrahydropyranyl group and a tetrahydrofuranyl group are preferable. Examples of the alkyl group or aralkyl group which may have a substituent include a methoxymethyl group, 1-
Examples include an alkoxyalkyl group such as an ethoxyethyl group and a 2-methoxyethoxymethyl group, and a benzyl group, a methoxybenzyl group, and a trityl group.

The protecting group for a hydroxyl group can be converted into a hydroxyl group by a conventional method. For example, "New Experimental Chemistry Course 14: Synthesis and Reaction of Organic Compounds (I), (II), (V)" (Maruzen), "Protective Groups in Organic Synthesis" (TW Greene, J. Wiley & S.)
ons), the compound can be easily converted to a hydroxyl group.

The starting alcohol having a hydroxyl group at the 15-position is fluorinated to form an ω having one fluorine atom at the 15-position.
A fluorinating agent is used when forming chained corely lactones. The fluorination is preferably performed in an inert solvent. The fluorination reaction may be performed in the presence of a base. The reaction temperature of the fluorination is usually -150 to +100
° C, and is preferably from -80 to + 60 ° C. In general, the amount of the fluorinating agent is preferably about 0.5 to 20 parts by weight, particularly preferably about 1 to 5 parts by weight, based on 1 part by weight of the raw material ketone as a substrate.

In the reaction of fluorinating the hydroxyl group of the raw material alcohol having a hydroxyl group at the 15-position to form a ω-chain-containing coreylactone having one fluorine atom at the 15-position, the hydroxyl group to be fluorinated and the steric configuration are different. Since a fluorine atom is easily introduced into the inverted configuration, a fluorinated product having the configuration is obtained as a main product. Therefore, in order to efficiently obtain a fluorinated product having the same configuration as the natural type hydroxyl group, it is preferable to use a raw material alcohol having a hydroxyl group in a configuration opposite to that of the natural type. When a functional group which may be fluorinated by the fluorination reaction is present in the alcohols, it is preferable to protect the functional group with a protecting group in advance. For example, when R ² is hydrogen, it is preferable to carry out a fluorination reaction by protecting with a protecting group, and then appropriately carry out deprotection. The fluorinating agent used in the fluorination is not particularly limited, and a known or well-known nucleophilic fluorinating agent can be used. For example, Tomoya Kitazume, Takashi Ishihara, Takeo Taguchi, "Fluorine Chemistry"
Nucleophilic fluorinating agents described in such books as Kodansha Scientific can be used.

Specific examples of the fluorinating agent include fluoroalkylamine reactants such as dialkylaminosulfur trifluoride derivative, tetrafluorophenylphosphorane, diethylamine-chlorotrifluoroethene adduct and diethylamine-hexafluoropropene adduct. Hydrogen fluoride amine complexes such as HF-pyridine and HF-triethylamine, silicon tetrafluoride, sulfur tetrafluoride, potassium fluoride,
Examples thereof include metal fluorides such as cesium fluoride and silver fluoride, and ammonium salts and phosphonium salts such as tetrabutylammonium fluoride, tetraethylammonium fluoride and tetrabutylphosphonium fluoride. Of these, particularly preferred nucleophilic fluorinating agents in terms of yield and selectivity are dialkylaminosulfur trifluoride derivatives, specifically, morpholinosulfatrifluoride, piperidinosulfatrifluoride, diethylaminosulfur Trifluoride, dimethylaminosulfur trifluoride and the like are preferred.

Since the fluorinating agent is a nucleophilic fluorinating agent, the hydroxyl group of alcohols may be directly fluorinated to form a fluoride. Further, in order to increase the reactivity of the hydroxyl group or suppress side reactions, the hydroxyl group may be converted to a derivative such as sulfonate or silyl ether and then fluorinated. As the sulfonate, methanesulfonate, p-
Preferred are toluenesulfonate, benzenesulfonate, trifluoromethanesulfonate and the like.

The inert solvent used for the fluorination reaction is preferably a halogen-based solvent, an ether-based solvent, a hydrocarbon-based solvent, an ester-based solvent, a polar solvent, or a mixed solvent thereof. In general, the amount of the inert solvent is preferably about 2 to 500 parts by weight, particularly preferably 5 to 100 parts by weight, based on 1 part by weight of the ketones. As the halogen-based solvent, methylene chloride, chloroform, 1,2-dichloroethane, carbon tetrachloride, chlorobenzene, dichloropentafluoropropane and the like are preferable. As ether solvents, diethyl ether, tetrahydrofuran [TH
F], 1,4-dioxane, dimethoxyethane, diglyme, t-butyl methyl ether and the like are preferred. As the hydrocarbon solvent, hexane, toluene, benzene, pentane, xylene, petroleum ether and the like are preferable. As the ester solvent, ethyl acetate, butyl acetate and the like are preferable. As polar solvents, dimethyl sulfoxide, hexamethylphosphoramide [HMPA], 1,3-dimethyl-3,4,5,6-tetrahydro-2 (1H) -pyrimidinone [DMPU], 1,3-dimethyl-2 -Imidazolidinone [DMI], N, N, N ', N'-tetramethylethylenediamine [TMEDA] and the like are preferable ([
] Are abbreviations). As the inert solvent, methylene chloride,
Chloroform, 1,2-dichloroethane, toluene and the like are preferred.

The fluorination reaction may be carried out in the presence of a base. As the base, amines such as tertiary amines and aromatic amines, and salts of alkali metals and alkaline earth metals are preferable. Specific examples include triethylamine, diisopropylethylamine, pyridine, 2,6-lutidine, dimethylaminopyridine, sodium carbonate, potassium carbonate, sodium hydrogencarbonate, potassium hydrogencarbonate and the like.

The lactones obtained by the above fluorination reaction are then reduced to produce lactols. This method can be carried out by reacting a reducing agent in an inert solvent. For example, it is described in “New Experimental Chemistry Lecture 15 Oxidation and Reduction (II)” (Maruzen), “Fourth Edition Experimental Chemistry Lecture 26 Organic Synthesis VIII, Asymmetric Synthesis / Reduction / Sugar / Labeled Compound” (Maruzen), and the like. The method can be adopted.

The amount of the reducing agent used in the reduction reaction is usually 0.1 to 1 equivalent of the lactone.
It is preferably from 01 to 50 equivalents, particularly preferably from 1 to 20 equivalents. The reaction temperature is preferably about -150 to + 100 ° C,
Particularly, -80 to 0 ° C is preferable.

Examples of the reducing agent include diisobutylaluminum hydride [DIBAH], dialkylaluminum alkoxide, lithium aluminum hydride, tributyltin hydride, triphenyltin hydride, triethylsilane, trichlorosilane, dimethylphenylsilane, diphenylsilane, and hydrogenated hydrogen. Sodium borohydride, sodium trimethoxyborohydride, lithium tri (s-butyl) borohydride, potassium tri (s-butyl) borohydride, lithium lithium triethylborohydride, lithium trisiamilborohydride, potassium trithiamylborohydride , Zinc borohydride, calcium borohydride, trialkoxyaluminum lithium hydride, sodium bis (2-methoxyethoxy) aluminum hydride, diborane, disiamilbo , Texylborane, 9-borabicyclo [3.3.1] nonane, and the like, diisobutylaluminum hydride [DIBAH], sodium bis (2-methoxyethoxy) aluminum hydride, disiamylborane, tri (s-butyl) hydride Lithium boron is preferred.

The inert solvent used for the reduction reaction is preferably an ether solvent, a hydrocarbon solvent, a polar solvent, or a mixed solvent thereof. Ether-based solvents, hydrocarbon-based solvents, specific examples of the polar solvent, the ether-based solvent described as a specific example in the description of the fluorination reaction,
Hydrocarbon solvents and polar solvents are preferred. Among them, diethyl ether, THF, t-butyl methyl ether and toluene are particularly preferred. In addition, the steric configuration of the hydroxyl group of lactols generated by the reduction reaction is not particularly limited.

As described above, the phosphoranes are obtained by reacting the corresponding phosphonium salts with a base in an inert solvent. The resulting phosphoranes are usually used without isolation for the Wittig reaction with lactols. Methods for producing phosphoranes from the corresponding phosphonium salts are described in, for example, "New Experimental Chemistry Course 14 Synthesis and Reaction of Organic Compounds (I)" (Maruzen), "Fourth Edition Experimental Chemistry Course 19"
Organic Synthesis I, Hydrocarbon / Halogen Compounds ”(Maruzen), and the method described by Schaaf et al.
ed. Chem. 22, 1340 (1979)).

The structure corresponding to Z in the phosphoranes or phosphonium salts may be any of the aforementioned Z, but is usually a hydroxyl group (-OR ^{3 in} which R ⁴ is a hydrogen atom). Therefore, when a lactol is allowed to act on the phosphorane, a fluorinated PG derivative in which Z is a hydroxyl group can be obtained. When manufacturing a fluorine-containing PG derivative in which Z is a group other than a hydroxyl group, it is preferable to use a method of converting a fluorine-containing PG derivative in which Z is a hydroxyl group into a group other than a hydroxyl group. In addition, Z may be a group other than a hydroxyl group before forming a phosphorane.

Further, Z of the phosphonium salt is -NHCO
When R ⁴ or —NHSO ₂ R ⁵ is converted to a phosphorane, the —NHCOR in the phosphorane is used.
Hydrogen atom bonded to the nitrogen atom of the ⁴ or -NHSO ₂ R ⁵ may be converted to metal ions. Further, when this is reacted with a lactol by the Wittig reaction, the corresponding portion of the resulting reaction product becomes a metal ion.
This metal ion is derived from the metal ion (particularly an alkali metal ion or an alkaline earth metal ion) of a base used when converting a phosphonium salt into a phosphorane. The metal ion can be finally converted to a hydrogen atom by a treatment such as hydrolysis.

Examples of the phosphonium salts include the following compounds, from which the corresponding phosphoranes are formed. (4-carboxybutyl)
Triphenylphosphonium bromide, (4-carboxy-3-oxabutyl) triphenylphosphonium bromide, [4- (N-methanesulfonyl) carbamoylbutyl] triphenylphosphonium bromide, [4- (N-
Benzoyl) carbamoylbutyl] triphenylphosphonium bromide, (4-carboxybutyl) tri (o-
(Tolyl) phosphonium bromide, (4-carboxybutyl) tri (m-tolyl) phosphonium bromide,
(Carboxybutyl) tri (p-tolyl) phosphonium bromide.

In general, the amount of the phosphorane used is preferably about 0.1 to 20 equivalents, more preferably 1 to 10 equivalents, per equivalent of the lactol. The reaction of causing a phosphorane to act on a lactol is a reaction generally called a Wittig reaction. For the reaction of the lactols and the phosphoranes in the present invention, conditions usually used for this Wittig reaction can be adopted. In particular, it is preferable to carry out the reaction under basic conditions, and further to carry out the reaction in an inert solvent. The reaction temperature is usually from -150 to +20
The temperature is preferably about 0 ° C, particularly preferably -80 to + 100 ° C. The amount of the base is usually one of lactols.
The equivalent is preferably about 1 to 20 equivalents, particularly 2 to 1 equivalent.
0 equivalents are preferred. The base can be selected in consideration of the acidity of hydrogen bonded to the carbon atom at the α-position of the phosphorus atom of the phosphonium salt, which is a raw material of the phosphorane, or the stability of the resulting phosphorane.

Specific examples of the base include the following. Sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium methoxide, sodium ethoxide, triethylamine, diisopropylethylamine, pyridine, N-methylmorpholine, 1,5
-Diazabicyclo [4.3.0] non-5-ene, 1,
8-diazabicyclo [5.4.0] undec-7-ene, potassium-t-butoxide, lithium amide, sodium amide, potassium amide, lithium diisopropylamide, lithium diethylamide, lithium dicyclohexylamide, lithium isopropylcyclohexylamide, lithium-2 , 2,6,6-tetramethylpiperidine, lithium bis (trimethylsilyl) amide, sodium diethylamide, sodium bis (trimethylsilyl) amide, potassium-3-aminopropylamide, potassium bis (trimethylsilyl) amide, lithium hydride, sodium hydride , Potassium hydride, sodium methylsulfinyl methylide, n-butyllithium, s-butyllithium, t-butyllithium, methyllithium, phenyllithium Beam, lithium naphthalenide,
Lithium biphenylide, sodium trityl.

Among these bases, potassium carbonate, potassium tert-butoxide, lithium amide, sodium amide, potassium amide, lithium diisopropylamide,
Lithium diethylamide, lithium dicyclohexylamide, lithium isopropylcyclohexylamide, lithium-2,2,6,6-tetramethylpiperidine, lithium bis (trimethylsilyl) amide, sodium diethylamide, sodium bis (trimethylsilyl) amide, potassium-3-aminopropylamide , Potassium bis (trimethylsilyl) amide and sodium methylsulfinylmethylide are preferred, and potassium t-butoxide, sodium bis (trimethylsilyl) amide, potassium bis (trimethylsilyl) amide and sodium methylsulfinylmethylide are particularly preferred.

As the inert solvent, ether solvents, hydrocarbon solvents, polar solvents, aqueous solvents, alcohol solvents,
Alternatively, a solvent containing two or more of these is preferable. The amount of the inert solvent used is usually one of lactols.
The amount is preferably about 5 to 1000 parts by weight, particularly preferably 10 to 100 parts by weight based on parts by weight. Specific examples of the ether solvent, the hydrocarbon solvent, and the polar solvent are preferably the ether solvents, hydrocarbon solvents, and polar solvents exemplified in the fluorination reaction. As the aqueous solvent, water or a mixed solvent of water and an alcohol solvent is preferable. As the alcohol solvent, methanol, ethanol, t-butanol, t-amyl alcohol and the like are preferable. Particularly preferred solvents include diethyl ether, THF, 1,2-dimethoxyethane, t-butyl methyl ether and toluene.

The obtained 15-deoxy-15-fluoro PG derivative can convert its Z to another Z if necessary. For example, when Z is a hydroxyl group, it can be appropriately converted into an ester, a salt of a carboxylic acid, an acylamide, a sulfonamide, a thioester, or the like by a conventional method.

The esterification of Z can be carried out by a conventional method, for example, “New Experimental Chemistry Course 14 Synthesis and Reaction of Organic Compounds”
(II) "(Maruzen) and the like. For example, methods such as esterification by condensation with alcohols and phenols, esterification with an O-alkylating agent, esterification with alkenes and alkynes, and esterification with dialkyl sulfates and halogenated hydrocarbons are used. Can be

Z is an acylamide, a sulfonamide,
For example, Tither
eley et al. (J. Chem. Soc., 85, 1673 (1904)), Lynch
(Can. J. Chem., 50, 2143 (1972)) and Davidson et al. (J Am. Chem. Soc., 80, 376 (1958)). Further, after converting the carboxylic acid to an acid halide or active ester, a method of directly condensing with an amide, a sulfonamide, or an amine, or reacting with an amine to convert to an amide, followed by acylation or A method of sulfonylation and the like are used.

As a method for converting Z into thioesters, see “New Experimental Chemistry Course 14 Synthesis and Reaction of Organic Compounds (II
I) "(Maruzen)," Protective Groups Inn
Organic Synthesis "(TW Greene
Author, J. et al. Wiley & Sons) can be employed. For example, a method in which a carboxylic acid is converted into an acid halide or an active ester and then reacted with a thiol is used.

A hydroxyl group is present at the 9-position or 11-position of the 15-deoxy-15-fluoro PG derivative, and a known oxidation reaction can be applied as a method for oxidizing the hydroxyl group. For example, “New Experimental Chemistry Course 15 Oxidation and Reduction (I-1), (I
-2) "(Maruzen)," Fourth Edition Experimental Chemistry Lecture 23 Organic Synthesis V "(Maruzen), etc., and chromic acid oxidation and oxidation with dimethyl sulfoxide are preferred.
Specifically, Jones oxidation, Collins oxidation, oxidation with pyridinium chlorochromate, Swern oxidation, and the like are preferable.

15-Deoxy-15-fluoro PGF ₂
Cyclizing the α derivative to form 15-deoxy-15-fluoro P
As a method of synthesizing a GI2 derivative, iodine, N-iodosuccinimide, N-bromosuccinimide, or the like is used in a cyclization reaction, a cyclized product is dehydrohalogenated in the presence of a base, or a mercury compound is used. And then a method of reducing the intermediate mercury compound. Preferably,
Iodine, N-iodosuccinimide, N-bromosuccinimide, or the like is used for the cyclization reaction, and the cyclized product is triethylamine, diisopropylethylamine, pyridine, N-methylmorpholine, 1,5-diazabicyclo [4.3.0].
Nona-5-ene, 1,8-diazabicyclo [5.4.
0] A method of dehydrohalogenating in the presence of an amine base such as undec-7-ene is used.

The 15-deoxy-15-fluoroPGE derivative is dehydrated to give 15-deoxy-15-fluoroPGE.
A derivative or 15-deoxy-15-fluoro PGB
Various known dehydrating agents can be used as a method for synthesizing the derivative and a method for dehydrating the 15-deoxy-15-fluoro PGD derivative to obtain the 15-deoxy-15-fluoro PGJ derivative. For example, the method described in “New Experimental Chemistry Course 14, Synthesis and Reaction of Organic Compounds (I)” (Maruzen) is used. Specifically, acids, bases, halogenating agents, sulfonating agents, esterifying agents, dehydrating agents and the like are widely used. Amines such as hydrochloric acid, sulfuric acid, acetic acid, sodium hydroxide, potassium hydroxide, pyridine, triethylamine, diisopropylethylamine, phosphoryl chloride, thionyl chloride, methanesulfonyl chloride, acetic anhydride, acetyl chloride, phosphorus pentoxide and the like and combinations thereof. Used.

Specific examples of the compound represented by the general formula (1) include, but are not limited to, the following compounds.

16- (3,5-dichlorophenoxy)-
15-deoxy-15-fluoro-17,18,19,
20-tetranor PGE ₂ methyl ester, 16-
(3,5-dichlorophenoxy) -15-deoxy-1
5-fluoro-17,18,19,20-tetranor P
GE ₂ ethyl ester, 16- (3,5-dichlorophenoxy) -15-deoxy-15-fluoro-17,1
8,19,20-tetranor PGE ₂ isopropyl ester, 16- (3,4-dichlorophenoxy) -15
Deoxy-15-fluoro-17,18,19,20-
Tetranor PGE ₂ methyl ester, 16- (3,4-
Dichlorophenoxy) -15-deoxy-15-fluoro-17,18,19,20-tetranor PGE ₂ ethyl ester, 16- (3,4-dichlorophenoxy)-
15-deoxy-15-fluoro-17,18,19,
20-tetranor PGE ₂ isopropyl ester, 16
-(3-chlorophenoxy) -15-deoxy-15-
Fluoro-17,18,19,20-tetranor PGE
_2- methyl ester, 16- (3-chlorophenoxy)-
15-deoxy-15-fluoro-17,18,19,
20-tetranor PGE ₂ ethyl ester, 16- (3
-Chlorophenoxy) -15-deoxy-15-fluoro-17,18,19,20-tetranor PGE ₂ isopropyl ester.

16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-17,18,
19,20-tetranor PGE ₂ methyl ester, 16
-(3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-17,18,19,20-tetranor PGE ₂ ethyl ester, 16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro -17,18,19,20-tetranor PGE ₂ isopropyl ester, 16-phenoxy-15-deoxy-15-fluoro-17,18,19,20-tetranor PGE ₂ methyl ester, 16-phenoxy-15
-Deoxy-15-fluoro-17,18,19,20
-Tetranor PGE ₂ ethyl ester, 16-phenoxy-15-deoxy-15-fluoro-17,18,1
9,20-tetranor PGE ₂ isopropyl ester.

17-phenyl-15-deoxy-15-
Fluoro-18,19,20-trinor PGE ₂ methyl ester, 17-phenyl-15-deoxy-15-fluoro-18,19,20-trinor PGE ₂ ethyl ester, 17-phenyl-15-deoxy-15-fluoro- 18,19,20-trinor PGE ₂ isopropyl ester.

15-deoxy-15-fluoro-13,
14-dihydro PGE ₂ methyl ester, 15-deoxy-15-fluoro-13,14-dihydro PGE ₂ ethyl ester, 15-deoxy-15-fluoro-1
3,14-dihydro PGE ₂ isopropyl ester.

16- (3,5-dichlorophenoxy)-
15-deoxy-15-fluoro-13,14-dihydro-17,18,19,20-tetranor PGE ₂ methyl ester, 16- (3,5-dichlorophenoxy)-
15-deoxy-15-fluoro-13,14-dihydro-17,18,19,20-tetranor PGE ₂ ethyl ester, 16- (3,5-dichlorophenoxy)-
15-deoxy-15-fluoro-13,14-dihydro-17,18,19,20-tetranor PGE ₂ isopropyl ester, 16- (3,4-dichlorophenoxy) -15-deoxy-15-fluoro-13,14 −
Dihydro-17,18,19,20-tetranor PGE
_2- methyl ester, 16- (3,4-dichlorophenoxy) -15-deoxy-15-fluoro-13,14-
Dihydro-17,18,19,20-tetranor PGE
_2- ethyl ester, 16- (3,4-dichlorophenoxy) -15-deoxy-15-fluoro-13,14-
Dihydro-17,18,19,20-tetranor PGE
₂ isopropyl ester.

16- (3-chlorophenoxy) -15-
Deoxy-15-fluoro-13,14-dihydro-1
7,18,19,20-tetranor PGE ₂ methyl ester, 16- (3-chlorophenoxy) -15-deoxy-15-fluoro-13,14-dihydro-17,1
8,19,20-tetranor PGE ₂ ethyl ester,
16- (3-chlorophenoxy) -15-deoxy-1
5-fluoro-13,14-dihydro-17,18,1
9,20-tetranor PGE ₂ isopropyl ester,
16- (3-trifluoromethylphenoxy) -15-
Deoxy-15-fluoro-13,14-dihydro-1
7,18,19,20-tetranor PGE ₂ methyl ester, 16- (3-trifluoromethylphenoxy)-
15-deoxy-15-fluoro-13,14-dihydro-17,18,19,20-tetranor PGE ₂ ethyl ester, 16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-13,14 −
Dihydro-17,18,19,20-tetranor PGE
₂ isopropyl ester.

16-phenoxy-15-deoxy-15
-Fluoro-13,14-dihydro-17,18,1
9,20-tetranor PGE ₂ methyl ester, 16-
Phenoxy-15-deoxy-15-fluoro-13,
14-dihydro-17,18,19,20-tetranor PGE ₂ ethyl ester, 16-phenoxy-15-deoxy-15-fluoro-13,14-dihydro-1
7,18,19,20-tetranor PGE ₂ isopropyl ester, 17-phenyl-15-deoxy-15-
Fluoro-13,14-dihydro-18,19,20-
Trinor PGE ₂ methyl ester, 17-phenyl-1
5-deoxy-15-fluoro-13,14-dihydro-18,19,20-trinor PGE ₂ ethyl ester, 17-phenyl-15-deoxy-15-fluoro-13,14-dihydro-18,19,20- Trinor PGE ₂ isopropyl ester, 15-deoxy-15
-Fluoro-3-oxa-17,18,19,20-tetranor PGE ₂ methyl ester, 15-deoxy-1
5-fluoro-3-oxa-17,18,19,20-
Tetranor PGE ₂ ethyl ester, 15-deoxy-
15-Fluoro-3-oxa-17,18,19,20
-Tetranor PGE ₂ isopropyl ester.

16- (3,5-dichlorophenoxy)-
15-deoxy-15-fluoro-3-oxa-17,
18,19,20-tetranor PGE ₂ methyl ester, 16- (3,5-dichlorophenoxy) -15-deoxy-15-fluoro-3-oxa-17,18,1
9,20-tetranor PGE ₂ ethyl ester, 16-
(3,5-dichlorophenoxy) -15-deoxy-1
5-fluoro-3-oxa-17,18,19,20-
Tetranor PGE ₂ isopropyl ester, 16-
(3,4-dichlorophenoxy) -15-deoxy-1
5-fluoro-3-oxa-17,18,19,20-
Tetranor PGE ₂ methyl ester, 16- (3,4-
Dichlorophenoxy) -15-deoxy-15-fluoro-3-oxa-17,18,19,20-tetranor PGE ₂ ethyl ester, 16- (3,4-dichlorophenoxy) -15-deoxy-15-fluoro-3 -Oxa-17,18,19,20-tetranor PGE ₂ isopropyl ester.

16- (3-chlorophenoxy) -15-
Deoxy-15-fluoro-3-oxa-17,18,
19,20-tetranor PGE ₂ methyl ester, 16
-(3-chlorophenoxy) -15-deoxy-15-
Fluoro-3-oxa-17,18,19,20-tetranor PGE ₂ ethyl ester, 16- (3-chlorophenoxy) -15-deoxy-15-fluoro-3-oxa-17,18,19,20-tetranor PGE ₂ isopropyl ester.

16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-3-oxa-
17,18,19,20-tetranor PGE ₂ methyl ester, 16- (3-trifluoromethylphenoxy)
-15-deoxy-15-fluoro-3-oxa-1
7,18,19,20-tetranor PGE ₂ ethyl ester, 16- (3-trifluoromethylphenoxy)-
15-deoxy-15-fluoro-3-oxa-17,
18,19,20-tetranor PGE ₂ isopropyl ester, 16-phenoxy-15-deoxy-15-fluoro-3-oxa-17,18,19,20-tetranor PGE ₂ methyl ester, 16-phenoxy-15
-Deoxy-15-fluoro-3-oxa-17,1
8,19,20-tetranor PGE ₂ ethyl ester,
16-phenoxy-15-deoxy-15-fluoro-
3-oxa-17,18,19,20-tetranor PG
E ₂ isopropyl ester, 17-phenyl-15-deoxy-15-fluoro-3-oxa-18,19,2
0-trinor PGE ₂ methyl ester, 17-phenyl-15-deoxy-15-fluoro-3-oxa-1
8,19,20-trinor PGE ₂ ethyl ester, 1
7-phenyl-15-deoxy-15-fluoro-3-
Oxa-18,19,20-trinor PGE ₂ isopropyl ester.

15-deoxy-15-fluoro-11-
Pivaloyl PGE ₂ methyl ester, 15-deoxy-
15-fluoro-11-pivaloyl PGE ₂ ethyl ester, 15-deoxy-15-fluoro-11-pivaloyl PGE ₂ isopropyl ester, 16- (3,5-
Dichlorophenoxy) -15-deoxy-15-fluoro-11-pivaloyl-17,18,19,20-tetranor PGE ₂ methyl ester, 16- (3,5-dichlorophenoxy) -15-deoxy-15-fluoro-
11-pivaloyl-17,18,19,20-tetranor PGE ₂ ethyl ester, 16- (3,5-dichlorophenoxy) -15-deoxy-15-fluoro-11
-Pivaloyl-17,18,19,20-tetranor P
GE ₂ isopropyl ester.

16- (3,4-dichlorophenoxy)-
15-deoxy-15-fluoro-11-pivaloyl-
17,18,19,20-tetranor PGE ₂ methyl ester, 16- (3,4-dichlorophenoxy) -15
-Deoxy-15-fluoro-11-pivaloyl-1
7,18,19,20-tetranor PGE ₂ ethyl ester, 16- (3,4-dichlorophenoxy) -15
Deoxy-15-fluoro-11-pivaloyl-17,
18,19,20-tetranor PGE ₂ isopropyl ester.

16- (3-chlorophenoxy) -15-
Deoxy-15-fluoro-11-pivaloyl-17,
18,19,20-tetranor PGE ₂ methyl ester, 16- (3-chlorophenoxy) -15-deoxy-15-fluoro-11-pivaloyl-17,18,1
9,20-tetranor PGE ₂ ethyl ester, 16-
(3-chlorophenoxy) -15-deoxy-15-fluoro-11-pivaloyl-17,18,19,20-
Tetranor PGE ₂ isopropyl ester.

16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-11-pivaloyl-17,18,19,20-tetranor PGE ₂ methyl ester, 16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-11-pivaloyl-17,18,19,20-tetranor PGE ₂
Ethyl ester, 16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-11-pivaloyl-17,18,19,20-tetranor PGE
_2- isopropyl ester, 16-phenoxy-15-deoxy-15-fluoro-11-pivaloyl-17,1
8,19,20-tetranor PGE ₂ methyl ester,
16-phenoxy-15-deoxy-15-fluoro-
11-pivaloyl-17,18,19,20-tetranor PGE ₂ ethyl ester, 16-phenoxy-15-
Deoxy-15-fluoro-11-pivaloyl-17,
18,19,20-tetranor PGE ₂ isopropyl ester.

17-phenyl-15-deoxy-15-
Fluoro-11-pivaloyl-18,19,20-trinor PGE ₂ methyl ester, 17-phenyl-15-
Deoxy-15-fluoro-11-pivaloyl-18,
19,20-trinor PGE ₂ ethyl ester, 17-
Phenyl-15-deoxy-15-fluoro-11-pivaloyl-18,19,20-trinor PGE ₂ isopropyl ester, 15-deoxy-15-fluoroPG
E ₂ 1,11-lactone, 16- (3,5-dichlorophenoxy) -15-deoxy-15-fluoro-17,
18,19,20-tetranor PGE ₂ 1,11-lactone, 16- (3,4-dichlorophenoxy) -15
Deoxy-15-fluoro-17,18,19,20-
Tetranor PGE ₂ 1,11-lactone, 16- (3-
Chlorophenoxy) -15-deoxy-15-fluoro-17,18,19,20-tetranor PGE ₂ 1,1
1-lactone, 16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-17,1
8,19,20-tetranor PGE ₂ 1,11-lactone.

16-phenoxy-15-deoxy-15
-Fluoro-17,18,19,20-tetranor PG
E ₂ 1,11-lactone, 17-phenyl-15-deoxy-15-fluoro-18,19,20-trinor P
GE ₂ 1,11-lactone, 15-deoxy-15-fluoro-17,18,19,20-tetranor PGE
_2, 16- (3,5-dichlorophenoxy) -15-deoxy-15-fluoro-tetranor-PGE _2, 16- (3,4-dichlorophenoxy) -15-deoxy-15- Fluoro-17,18,
19,20-tetranor PGE ₂ , 16- (3-chlorophenoxy) -15-deoxy-15-fluoro-1
7,18,19,20-tetranor PGE ₂ , 16-
(3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-17,18,19,20-tetranor PGE ₂ , 16-phenoxy-15-deoxy-1
5-fluoro-17,18,19,20-tetranor P
GE _2, 17-phenyl-15-deoxy-15-fluoro-18,19,20-trinor PGE _2, 15-deoxy-15-fluoro-13,14-dihydro-PGE
₂ .

16- (3,5-dichlorophenoxy)-
15-deoxy-15-fluoro-13,14-dihydro-17,18,19,20-tetranor PGE ₂ , 1
6- (3,4-dichlorophenoxy) -15-deoxy-15-fluoro-13,14-dihydro-17,1
8,19,20-tetranor PGE ₂ , 16- (3-chlorophenoxy) -15-deoxy-15-fluoro-
13,14-dihydro-17,18,19,20-tetranor PGE ₂ , 16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-13,1
4-dihydro-17,18,19,20-tetranor P
GE _2, 16- phenoxy-15-deoxy-15-fluoro-13,14-dihydro -17,18,19,2
0-tetranor PGE ₂ , 17-phenyl-15-deoxy-15-fluoro-13,14-dihydro-18,
19,20-trinor PGE ₂ , 15-deoxy-15
-Fluoro-3-oxa-17,18,19,20-tetranor PGE ₂ , 16- (3,5-dichlorophenoxy) -15-deoxy-15-fluoro-3-oxa-
17, 18, 19, 20-tetranor PGE ₂ , 16-
(3,4-dichlorophenoxy) -15-deoxy-1
5-fluoro-3-oxa-17,18,19,20-
Tetranor PGE ₂ , 16- (3-chlorophenoxy)
-15-deoxy-15-fluoro-3-oxa-1
7,18,19,20-tetranor PGE ₂ , 16-
(3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-13,14-dihydro-3-oxa-tetranor-PGE _2.

16-phenoxy-15-deoxy-15
-Fluoro-13,14-dihydro-3-oxa-1
7,18,19,20-tetranor PGE ₂ , 17-phenyl-15-deoxy-15-fluoro-13,14
-Dihydro-3-oxa-18,19,20-trinor PGE ₂ , N-methanesulfonyl-15-deoxy-1
5-fluoro-17,18,19,20-tetranor P
GE ₂ carboxamide, N-methanesulfonyl-16
(3,5-dichlorophenoxy) -15-deoxy-1
5-fluoro-17,18,19,20-tetranor P
GE ₂ carboxamide, N-methanesulfonyl-16
(3,4-dichlorophenoxy) -15-deoxy-1
5-fluoro-17,18,19,20-tetranor P
GE ₂ carboxamide, N-methanesulfonyl-16
(3-Chlorophenoxy) -15-deoxy-15-fluoro-17,18,19,20-tetranor PGE ₂
Carboxamide, N-methanesulfonyl-16- (3-
Trifluoromethylphenoxy) -15-deoxy-1
5-fluoro-17,18,19,20-tetranor P
GE ₂ carboxamide, N-methanesulfonyl-16
Phenoxy-15-deoxy-15-fluoro-17,
18,19,20-tetranor PGE ₂ carboxamide, N-methanesulfonyl-17-phenyl-15-deoxy-15-fluoro-18,19,20-trinor PGE ₂ carboxamide, 11,15-dideoxy-1
5-fluoro-PGE ₁ methyl ester.

11,15-dideoxy-15-fluoro-PGE ₁ ethyl ester, 11,15-dideoxy-
15-fluoro-PGE ₁ isopropyl ester, 16
-(3,5-dichlorophenoxy) -11,15-dideoxy-15-fluoro-17,18,19,20-tetranor PGE ₁ methyl ester, 16- (3,5-dichlorophenoxy) -11,15-dideoxy -15-
Fluoro-17,18,19,20-tetranor PGE
₁ ethyl ester, 16- (3,5-dichlorophenoxy) -11,15-dideoxy-15-fluoro-1
7,18,19,20-tetranor PGE ₁ isopropyl ester, 16- (3,4-dichlorophenoxy)-
11,15-dideoxy-15-fluoro-17,1
8,19,20-tetranor PGE ₁ methyl ester,
16- (3,4-dichlorophenoxy) -11,15-
Dideoxy-15-fluoro-17,18,19,20
-Tetranor PGE ₁ ethyl ester, 16- (3,4
-Dichlorophenoxy) -11,15-dideoxy-1
5-fluoro-17,18,19,20-tetranor P
GE ₁ isopropyl ester.

16- (3-chlorophenoxy) -11,
15-dideoxy-15-fluoro-17,18,1
9,20-tetranor PGE ₁ methyl ester, 16-
(3-chlorophenoxy) -11,15-dideoxy-
15-Fluoro-17,18,19,20-tetranor PGE ₁ ethyl ester, 16- (3-chlorophenoxy) -11,15-dideoxy-15-fluoro-1
7,18,19,20-tetranor PGE ₁ isopropyl ester, 16- (3-trifluoromethylphenoxy) -11,15-dideoxy-15-fluoro-1
7,18,19,20-tetranor PGE ₁ methyl ester, 16- (3-trifluoromethylphenoxy)-
11,15-dideoxy-15-fluoro-17,1
8,19,20-tetranor PGE ₁ ethyl ester,
16- (3-trifluoromethylphenoxy) -11,
15-dideoxy-15-fluoro-17,18,1
9,20-tetranor PGE ₁ isopropyl ester.

16-phenoxy-11,15-dideoxy-15-fluoro-17,18,19,20-tetranor PGE ₁ methyl ester, 16-phenoxy-1
1,15-dideoxy-15-fluoro-17,18,
19,20-tetranor PGE ₁ ethyl ester, 16
- phenoxy -11,15- dideoxy-15-fluoro-tetranor-PGE ₁ isopropyl ester, 17-phenyl -11,15- dideoxy-15-fluoro-18,19,20-trinor PGE ₁ Methyl ester, 17-phenyl-11,15
-Dideoxy-15-fluoro-18,19,20-trinor PGE ₁ ethyl ester, 17-phenyl-1
1,15-dideoxy-15-fluoro-18,19,
20-trinor PGE ₁ isopropyl ester, 11,
15-dideoxy-15-fluoro-13,14-dihydroPGE ₁ methyl ester, 11,15-dideoxy-15-fluoro-13,14-dihydroPGE ₁ ethyl ester, 11,15-dideoxy-15-fluoro-13, 14-dihydro PGE ₁ isopropyl ester.

16- (3,5-dichlorophenoxy)-
11,15-dideoxy-15-fluoro-13,14
-Dihydro-17,18,19,20-tetranor PG
E ₁ methyl ester, 16- (3,5-dichlorophenoxy) -11,15-dideoxy-15-fluoro-1
3,14-dihydro-17,18,19,20-tetranor PGE ₁ ethyl ester, 16- (3,5-dichlorophenoxy) -11,15-dideoxy-15-fluoro-13,14-dihydro-17,18 , 19,20
-Tetranor PGE ₁ isopropyl ester, 16-
(3,4-dichlorophenoxy) -11,15-dideoxy-15-fluoro-13,14-dihydro-17,
18,19,20-tetranor PGE ₁ methyl ester, 16- (3,4-dichlorophenoxy) -11,1
5-dideoxy-15-fluoro-13,14-dihydro-17,18,19,20-tetranor PGE ₁ ethyl ester, 16- (3,4-dichlorophenoxy)-
11,15-dideoxy-15-fluoro-13,14
-Dihydro-17,18,19,20-tetranor PG
E ₁ Isofluoroester, 16- (3-chlorophenoxy) -1
1,15-dideoxy-15-fluoro-13,14-
Dihydro-17,18,19,20-tetranor PGE
₁ methyl ester, 16- (3-chlorophenoxy)-
11,15-dideoxy-15-fluoro-13,14
-Dihydro-17,18,19,20-tetranor PG
E ₁ ethyl ester, 16- (3-chlorophenoxy)
-11,15-dideoxy-15-fluoro-13,1
4-dihydro-17,18,19,20-tetranor P
GE ₁ isopropyl ester.

16- (3-trifluoromethylphenoxy) -11,15-dideoxy-15-fluoro-1
3,14-dihydro-17,18,19,20-tetranor PGE ₁ methyl ester, 16- (3-trifluoromethylphenoxy) -11,15-dideoxy-15
-Fluoro-13,14-dihydro-17,18,1
9,20-tetranor PGE ₁ ethyl ester, 16-
(3-trifluoromethylphenoxy) -11,15-
Dideoxy-15-fluoro-13,14-dihydro-
17,18,19,20-tetranor PGE ₁ isopropyl ester, 16-phenoxy-11,15-dideoxy-15-fluoro-13,14-dihydro-17,
18,19,20-tetranor PGE ₁ methyl ester, 16-phenoxy-11,15-dideoxy-15
-Fluoro-13,14-dihydro-17,18,1
9,20-tetranor PGE ₁ ethyl ester, 16-
Phenoxy-11,15-dideoxy-15-fluoro-13,14-dihydro-17,18,19,20-tetranor PGE ₁ isopropyl ester, 17-phenyl-11,15-dideoxy-15-fluoro-13,
14-dihydro-18,19,20-trinor PGE ₁
Methyl ester, 17-phenyl-11,15-dideoxy-15-fluoro-13,14-dihydro-18,
19,20-trinor PGE ₁ ethyl ester, 17-
Phenyl-11,15-dideoxy-15-fluoro-
13,14-dihydro-18,19,20-trinor P
GE ₁ isopropyl ester.

11,15-dideoxy-15-fluoro-3-oxa-17,18,19,20-tetranor P
GE ₁ methyl ester, 11,15-dideoxy-15
-Fluoro-3-oxa-17,18,19,20-tetranor PGE ₁ ethyl ester, 11,15-dideoxy-15-fluoro-3-oxa-17,18,1
9,20-tetranor PGE ₁ isopropyl ester,
16- (3,5-dichlorophenoxy) -11,15-
Dideoxy-15-fluoro-3-oxa-17,1
8,19,20-tetranor PGE ₁ methyl ester,
16- (3,5-dichlorophenoxy) -11,15-
Dideoxy-15-fluoro-3-oxa-17,1
8,19,20-tetranor PGE ₁ ethyl ester,
16- (3,5-dichlorophenoxy) -11,15-
Dideoxy-15-fluoro-3-oxa-17,1
8,19,20-tetranor PGE ₁ isopropyl ester, 16- (3,4-dichlorophenoxy) -11,
15-dideoxy-15-fluoro-3-oxa-1
7,18,19,20-tetranor PGE ₁ methyl ester, 16- (3,4-dichlorophenoxy) -11,
15-dideoxy-15-fluoro-3-oxa-1
7,18,19,20-tetranor PGE ₁ ethyl ester, 16- (3,4-dichlorophenoxy) -11,
15-dideoxy-15-fluoro-3-oxa-1
7,18,19,20-tetranor PGE ₁ isopropyl ester.

16- (3-chlorophenoxy) -11,
15-dideoxy-15-fluoro-3-oxa-1
7,18,19,20-tetranor PGE ₁ methyl ester, 16- (3-chlorophenoxy) -11,15-
Dideoxy-15-fluoro-3-oxa-17,1
8,19,20-tetranor PGE ₁ ethyl ester,
16- (3-chlorophenoxy) -11,15-dideoxy-15-fluoro-3-oxa-17,18,1
9,20-tetranor PGE ₁ isopropyl ester,
16- (3-trifluoromethylphenoxy) -11,
15-dideoxy-15-fluoro-3-oxa-1
7,18,19,20-tetranor PGE ₁ methyl ester, 16- (3-trifluoromethylphenoxy)-
11,15-dideoxy-15-fluoro-3-oxa-17,18,19,20-tetranor PGE ₁ ethyl ester, 16- (3-trifluoromethylphenoxy) -11,15-dideoxy-15-fluoro-3 −
Oxa-17,18,19,20-tetranor PGE ₁
Isopropyl ester, 16-phenoxy-11,15
-Dideoxy-15-fluoro-3-oxa-17,1
8,19,20-tetranor PGE ₁ methyl ester,
16-phenoxy-11,15-dideoxy-15-fluoro-3-oxa-17,18,19,20-tetranor PGE ₁ ethyl ester, 16-phenoxy-1
1,15-dideoxy-15-fluoro-3-oxa-
17,18,19,20-tetranor PGE ₁ isopropyl ester.

17-phenyl-11,15-dideoxy-15-fluoro-3-oxa-18,19,20-trinor PGE ₁ methyl ester, 17-phenyl-1
1,15-dideoxy-15-fluoro-3-oxa-
18,19,20-trinor PGE ₁ ethyl ester,
17-phenyl-11,15-dideoxy-15-fluoro-3-oxa-18,19,20-trinor PGE
_1- isopropyl ester, 11,15-dideoxy-1
5-fluoro-17,18,19,20-tetranor P
GE _1, 16- (3,5- dichlorophenoxy) -1
1,15-dideoxy-15-fluoro-17,18,
19,20-tetranor PGE ₁ , 16- (3,4-dichlorophenoxy) -11,15-dideoxy-15-
Fluoro-17,18,19,20-tetranor PGE
₁ , 16- (3-chlorophenoxy) -11,15-dideoxy-15-fluoro-17,18,19,20-
Tetranor PGE ₁ , 16- (3-trifluoromethylphenoxy) -11,15-dideoxy-15-fluoro-17,18,19,20-tetranor PGE ₁ , 1
6-phenoxy-11,15-dideoxy-15-fluoro-17,18,19,20-tetranor PGE ₁ .

17-phenyl-11,15-dideoxy-15-fluoro-18,19,20-trinor PGE
_1, 11,15- dideoxy-15-fluoro-13
14-dihydroPGE ₁ , 16- (3,5-dichlorophenoxy) -11,15-dideoxy-15-fluoro-13,14-dihydro-17,18,19,20-tetranor PGE ₁ , 16- (3 4-dichlorophenoxy) -11,15-dideoxy-15-fluoro-1
3,14-dihydro-17,18,19,20-tetranor PGE ₁ , 16- (3-chlorophenoxy) -1
1,15-dideoxy-15-fluoro-13,14-
Dihydro-17,18,19,20-tetranor PGE
₁ , 16- (3-trifluoromethylphenoxy) -1
1,15-dideoxy-15-fluoro-13,14-
Dihydro-17,18,19,20-tetranor PGE
_1, 16-phenoxy -11,15- dideoxy -15
-Fluoro-13,14-dihydro-17,18,1
9,20-tetranor PGE ₁ , 17-phenyl-1
1,15-dideoxy-15-fluoro-13,14-
Dihydro-18,19,20-trinor PGE ₁ , 1
1,15-dideoxy-15-fluoro-3-oxa-
17, 18, 19, 20-tetranor PGE ₁ .

16- (3,5-dichlorophenoxy)-
11,15-dideoxy-15-fluoro-3-oxa-17,18,19,20-tetranor PGE ₁ , 16
-(3,4-dichlorophenoxy) -11,15-dideoxy-15-fluoro-3-oxa-17,18,1
9,20-tetranor PGE ₁ , 16- (3-chlorophenoxy) -11,15-dideoxy-15-fluoro-3-oxa-17,18,19,20-tetranor P
GE _1, 16- (3- trifluoromethylphenoxy)
-11,15-dideoxy-15-fluoro-13,1
4-dihydro-3-oxa-17,18,19,20-
Tetranor PGE ₁ , 16-phenoxy-11,15-
Dideoxy-15-fluoro-13,14-dihydro-
3-oxa-17,18,19,20-tetranor PG
E _1, 17- phenyl -11,15- dideoxy -15
-Fluoro-13,14-dihydro-3-oxa-1
8,19,20-trinor PGE ₁ .

N-methanesulfonyl-11,15-dideoxy-15-fluoro-17,18,19,20-tetranor PGE ₁ carboxamide, N-methanesulfonyl-16- (3,5-dichlorophenoxy) -11,1
5-dideoxy-15-fluoro-17,18,19,
20-tetranor PGE ₁ carboxamide, N-methanesulfonyl-16- (3,4-dichlorophenoxy)-
11,15-dideoxy-15-fluoro-17,1
8,19,20-tetranor PGE ₁ carboxamide,
N-methanesulfonyl-16- (3-chlorophenoxy) -11,15-dideoxy-15-fluoro-1
7,18,19,20-tetranor PGE ₁ carboxamide, N-methanesulfonyl-16- (3-trifluoromethylphenoxy) -11,15-dideoxy-15
-Fluoro-17,18,19,20-tetranor PG
E ₁ carboxamide, N-methanesulfonyl-16-phenoxy-11,15-dideoxy-15-fluoro-
17,18,19,20-tetranor PGE ₁ carboxamide, N-methanesulfonyl-17-phenyl-1
1,15-dideoxy-15-fluoro-18,19,
20-trinor PGE ₁ carboxamide.

15-Deoxy-15-fluoro-PGE
₁ methyl ester, 15-deoxy-15-fluoro-
PGE ₁ ethyl ester, 15-deoxy-15-fluoro-PGE ₁ isopropyl ester, 16- (3,5
-Dichlorophenoxy) -15-deoxy-15-fluoro-17,18,19,20-tetranor PGE ₁ methyl ester, 16- (3,5-dichlorophenoxy)
-15-deoxy-15-fluoro-17,18,1
9,20-tetranor PGE ₁ ethyl ester, 16-
(3,5-dichlorophenoxy) -15-deoxy-1
5-fluoro-17,18,19,20-tetranor P
GE ₁ isopropyl ester, 16- (3,4-dichlorophenoxy) -15-deoxy-15-fluoro-1
7,18,19,20-tetranor PGE ₁ methyl ester, 16- (3,4-dichlorophenoxy) -15
Deoxy-15-fluoro-17,18,19,20-
Tetranor PGE ₁ ethyl ester, 16- (3,4-
Dichlorophenoxy) -15-deoxy-15-fluoro-17,18,19,20-tetranor PGE ₁ isopropyl ester.

16- (3-chlorophenoxy) -15-
Deoxy-15-fluoro-17,18,19,20-
Tetranor PGE ₁ methyl ester, 16- (3-chlorophenoxy) -15-deoxy-15-fluoro-1
7,18,19,20-tetranor PGE ₁ ethyl ester, 16- (3-chlorophenoxy) -15-deoxy-15-fluoro-17,18,19,20-tetranor PGE ₁ isopropyl ester, 16- (3- (Trifluoromethylphenoxy) -15-deoxy-15-
Fluoro-17,18,19,20-tetranor PGE
₁ methyl ester, 16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-17,
18,19,20-tetranor PGE ₁ ethyl ester, 16- (3-trifluoromethylphenoxy) -1
5-deoxy-15-fluoro-17,18,19,2
0-tetranor PGE ₁ isopropyl ester, 16-
Phenoxy-15-deoxy-15-fluoro-17,
18,19,20-tetranor PGE ₁ methyl ester, 16-phenoxy-15-deoxy-15-fluoro-17,18,19,20-tetranor PGE ₁ ethyl ester, 16-phenoxy-15-deoxy-15
-Fluoro-17,18,19,20-tetranor PG
E ₁ Isopropyl ester.

17-phenyl-15-deoxy-15-
Fluoro-18,19,20-trinor PGE ₁ methyl ester, 17-phenyl-15-deoxy-15-fluoro-18,19,20-trinor PGE ₁ ethyl ester, 17-phenyl-15-deoxy-15-fluoro- 18,19,20-trinor PGE ₁ isopropyl ester, 15-deoxy-15-fluoro-13,
14-dihydroPGE ₁ methyl ester, 15-deoxy-15-fluoro-13,14-dihydroPGE ₁ ethyl ester, 15-deoxy-15-fluoro-1
3,14-dihydroPGE ₁ isopropyl ester, 1
6- (3,5-dichlorophenoxy) -15-deoxy-15-fluoro-13,14-dihydro-17,1
8,19,20-tetranor PGE ₁ methyl ester,
16- (3,5-dichlorophenoxy) -15-deoxy-15-fluoro-13,14-dihydro-17,1
8,19,20-tetranor PGE ₁ ethyl ester,
16- (3,5-dichlorophenoxy) -15-deoxy-15-fluoro-13,14-dihydro-17,1
8,19,20-tetranor PGE ₁ isopropyl ester.

16- (3,4-dichlorophenoxy)-
15-deoxy-15-fluoro-13,14-dihydro-17,18,19,20-tetranor PGE ₁ methyl ester, 16- (3,4-dichlorophenoxy)-
15-deoxy-15-fluoro-13,14-dihydro-17,18,19,20-tetranor PGE ₁ ethyl ester, 16- (3,4-dichlorophenoxy)-
15-deoxy-15-fluoro-13,14-dihydro-17,18,19,20-tetranor PGE ₁ isopropyl ester, 16- (3-chlorophenoxy)-
15-deoxy-15-fluoro-13,14-dihydro-17,18,19,20-tetranor PGE ₁ methyl ester, 16- (3-chlorophenoxy) -15
Deoxy-15-fluoro-13,14-dihydro-1
7,18,19,20-tetranor PGE ₁ ethyl ester, 16- (3-chlorophenoxy) -15-deoxy-15-fluoro-13,14-dihydro-17,1
8,19,20-tetranor PGE ₁ isopropyl ester, 16- (3-trifluoromethylphenoxy)-
15-deoxy-15-fluoro-13,14-dihydro-17,18,19,20-tetranor PGE ₁ methyl ester, 16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-13,14 −
Dihydro-17,18,19,20-tetranor PGE
₁ ethyl ester, 16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-13,
14-dihydro-17,18,19,20-tetranor PGE ₁ isopropyl ester.

16-phenoxy-15-deoxy-15
-Fluoro-13,14-dihydro-17,18,1
9,20-tetranor PGE ₁ methyl ester, 16-
Phenoxy-15-deoxy-15-fluoro-13,
14-dihydro-17,18,19,20-tetranor PGE ₁ ethyl ester, 16-phenoxy-15-deoxy-15-fluoro-13,14-dihydro-1
7,18,19,20-tetranor PGE ₁ isopropyl ester, 17-phenyl-15-deoxy-15-
Fluoro-13,14-dihydro-18,19,20-
Trinor PGE ₁ methyl ester, 17-phenyl-1
5-deoxy-15-fluoro-13,14-dihydro-18,19,20-trinor PGE ₁ ethyl ester, 17-phenyl-15-deoxy-15-fluoro-13,14-dihydro-18,19,20- Trinor PGE ₁ isopropyl ester, 15-deoxy-15
-Fluoro-3-oxa-17,18,19,20-tetranor PGE ₁ methyl ester, 15-deoxy-1
5-fluoro-3-oxa-17,18,19,20-
Tetranor PGE ₁ ethyl ester, 15-deoxy-
15-Fluoro-3-oxa-17,18,19,20
-Tetranor PGE ₁ isopropyl ester.

16- (3,5-dichlorophenoxy)-
15-deoxy-15-fluoro-3-oxa-17,
18,19,20-tetranor PGE ₁ methyl ester, 16- (3,5-dichlorophenoxy) -15-deoxy-15-fluoro-3-oxa-17,18,1
9,20-tetranor PGE ₁ ethyl ester, 16-
(3,5-dichlorophenoxy) -15-deoxy-1
5-fluoro-3-oxa-17,18,19,20-
Tetranor PGE ₁ isopropyl ester, 16-
(3,4-dichlorophenoxy) -15-deoxy-1
5-fluoro-3-oxa-17,18,19,20-
Tetranor PGE ₁ methyl ester, 16- (3,4-
Dichlorophenoxy) -15-deoxy-15-fluoro-3-oxa-17,18,19,20-tetranor PGE ₁ ethyl ester, 16- (3,4-dichlorophenoxy) -15-deoxy-15-fluoro-3 -Oxa-17,18,19,20-tetranor PGE ₁ isopropyl ester.

16- (3-chlorophenoxy) -15-
Deoxy-15-fluoro-3-oxa-17,18,
19,20-tetranor PGE ₁ methyl ester, 16
-(3-chlorophenoxy) -15-deoxy-15-
Fluoro-3-oxa-17,18,19,20-tetranor PGE ₁ ethyl ester, 16- (3-chlorophenoxy) -15-deoxy-15-fluoro-3-oxa-17,18,19,20-tetranor PGE ₁ isopropyl ester, 16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-3-
Oxa-17,18,19,20-tetranor PGE ₁
Methyl ester, 16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-3-oxa-17,18,19,20-tetranor PGE ₁ ethyl ester, 16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-3-oxa-
17,18,19,20-tetranor PGE ₁ isopropyl ester, 16-phenoxy-15-deoxy-1
5-fluoro-3-oxa-17,18,19,20-
Tetranor PGE ₁ methyl ester, 16-phenoxy-15-deoxy-15-fluoro-3-oxa-1
7,18,19,20-tetranor PGE ₁ ethyl ester, 16-phenoxy-15-deoxy-15-fluoro-3-oxa-17,18,19,20-tetranor PGE ₁ isopropyl ester.

17-phenyl-15-deoxy-15-
Fluoro-3-oxa-18,19,20-trinor P
GE ₁ methyl ester, 17-phenyl-15-deoxy-15-fluoro-3-oxa-18,19,20-
Trinor PGE ₁ ethyl ester, 17-phenyl-1
5-deoxy-15-fluoro-3-oxa-18,1
9,20-trinor PGE ₁ isopropyl ester, 1
5-deoxy-15-fluoro-11-pivaloyl PG
E ₁ methyl ester, 15-deoxy-15-fluoro-11-pivaloyl PGE ₁ ethyl ester, 15-deoxy-15-fluoro-11-pivaloyl PGE ₁ isopropyl ester, 16- (3,5-dichlorophenoxy) -15 Deoxy-15-fluoro-11-pivaloyl-17,18,19,20-tetranor PGE ₁
Methyl ester, 16- (3,5-dichlorophenoxy) -15-deoxy-15-fluoro-11-pivaloyl-17,18,19,20-tetranor PGE ₁ ethyl ester, 16- (3,5-dichlorophenoxy)
-15-deoxy-15-fluoro-11-pivaloyl-17,18,19,20-tetranor PGE ₁ isopropyl ester.

16- (3,4-dichlorophenoxy)-
15-deoxy-15-fluoro-11-pivaloyl-
17,18,19,20-tetranor PGE ₁ methyl ester, 16- (3,4-dichlorophenoxy) -15
-Deoxy-15-fluoro-11-pivaloyl-1
7,18,19,20-tetranor PGE ₁ ethyl ester, 16- (3,4-dichlorophenoxy) -15-
Deoxy-15-fluoro-11-pivaloyl-17,
18,19,20-tetranor PGE ₁ isopropyl ester, 16- (3-chlorophenoxy) -15-deoxy-15-fluoro-11-pivaloyl-17,1
8,19,20-tetranor PGE ₁ methyl ester,
16- (3-chlorophenoxy) -15-deoxy-1
5-fluoro-11-pivaloyl-17,18,19,
20-tetranor PGE ₁ ethyl ester, 16- (3
-Chlorophenoxy) -15-deoxy-15-fluoro-11-pivaloyl-17,18,19,20-tetranor PGE ₁ isopropyl ester.

16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-11-pivaloyl-17,18,19,20-tetranor PGE ₁ methyl ester, 16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-11-pivaloyl-17,18,19,20-tetranor PGE ₁
Ethyl ester, 16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-11-pivaloyl-17,18,19,20-tetranor PGE
₁ isopropyl ester, 16-phenoxy-15-deoxy-15-fluoro-11-pivaloyl-17,1
8,19,20-tetranor PGE ₁ methyl ester,
16-phenoxy-15-deoxy-15-fluoro-
11-pivaloyl-17,18,19,20-tetranor PGE ₁ ethyl ester, 16-phenoxy-15-
Deoxy-15-fluoro-11-pivaloyl-17,
18,19,20-tetranor PGE ₁ isopropyl ester.

17-phenyl-15-deoxy-15-
Fluoro-11-pivaloyl-18,19,20-trinor PGE ₁ methyl ester, 17-phenyl-15-
Deoxy-15-fluoro-11-pivaloyl-18,
19,20-trinor PGE ₁ ethyl ester, 17-
Phenyl-15-deoxy-15-fluoro-11-pivaloyl-18,19,20-trinor PGE ₁ isopropyl ester, 15-deoxy-15,15-difluoro PGE ₁ 1,11-lactone.

16- (3,5-dichlorophenoxy)-
15-deoxy-15-fluoro-17,18,19,
20-tetranor PGE ₁ 1,11-lactone, 16-
(3,4-dichlorophenoxy) -15-deoxy-1
5-fluoro-17,18,19,20-tetranor P
GE ₁ 1,11-lactone, 16- (3-chlorophenoxy) -15-deoxy-15-fluoro-17,1
8,19,20-tetranor PGE _11, 11-lactone, 16- (3-trifluoromethylphenoxy) -1
5-deoxy-15-fluoro-17,18,19,2
0-tetranor PGE ₁ 1,11-lactone, 16-phenoxy-15-deoxy-15-fluoro-17,1
8,19,20-tetranor PGE _11, 11-lactone, 17-phenyl-15-deoxy-15-fluoro-18,19,20-trinor PGE _1, 11-lactone, 15-deoxy-15-fluoro- 17, 18,
19,20-tetranor PGE ₁ .

16- (3,5-dichlorophenoxy)-
15-deoxy-15-fluoro-17,18,19,
20-tetranor PGE ₁ , 16- (3,4-dichlorophenoxy) -15-deoxy-15-fluoro-1
7,18,19,20- tetranor PGE _1, 16-
(3-Chlorophenoxy) -15-deoxy-15-fluoro-17,18,19,20-tetranor PGE
₁ , 16- (3-trifluoromethylphenoxy) -1
5-deoxy-15-fluoro-17,18,19,2
0-tetranor PGE ₁ , 16-phenoxy-15-deoxy-15-fluoro-17,18,19,20-tetranor PGE ₁ , 17-phenyl-15-deoxy-
15-Fluoro-18,19,20-trinor PGE
_1, 15-deoxy-15-fluoro-13,14-dihydro-PGE _1, 16- (3,5-dichlorophenoxy) -15-deoxy-15-fluoro-13,14
Dihydro-17,18,19,20-tetranor PGE
_1, 16- (3,4-dichlorophenoxy) -15-deoxy-15-fluoro-13,14-dihydro-1
7,18,19,20- tetranor PGE _1.

16- (3-chlorophenoxy) -15-
Deoxy-15-fluoro-13,14-dihydro-1
7,18,19,20- tetranor PGE _1, 16-
(3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-13,14-dihydro-17,
18,19,20-tetranor PGE ₁ , 16-phenoxy-15-deoxy-15-fluoro-13,14-
Dihydro-17,18,19,20-tetranor PGE
_1, 17-phenyl-15-deoxy-15-fluoro-13,14-dihydro-18,19,20-trinor PGE _1, 15-deoxy-15-fluoro-3-oxa-17,18,19,20 Tetranor PGE ₁ , 1
6- (3,5-dichlorophenoxy) -15-deoxy-15-fluoro-3-oxa-17,18,19,2
0-tetranor PGE ₁ , 16- (3,4-dichlorophenoxy) -15-deoxy-15-fluoro-3-oxa-17,18,19,20-tetranor PGE ₁ ,
16- (3-chlorophenoxy) -15-deoxy-1
5-fluoro-3-oxa-17,18,19,20-
Tetranor PGE ₁ , 16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-1
3,14-dihydro-3-oxa-17,18,19,
20-tetranor PGE ₁ .

16-phenoxy-15-deoxy-15
-Fluoro-13,14-dihydro-3-oxa-1
7,18,19,20-tetranor PGE ₁ , 17-phenyl-15-deoxy-15-fluoro-13,14
-Dihydro-3-oxa-18,19,20-trinor PGE ₁ , N-methanesulfonyl-15-deoxy-1
5-fluoro-17,18,19,20-tetranor P
GE ₁ carboxamide, N-methanesulfonyl-16
(3,5-dichlorophenoxy) -15-deoxy-1
5-fluoro-17,18,19,20-tetranor P
GE ₁ carboxamide, N-methanesulfonyl-16
(3,4-dichlorophenoxy) -15-deoxy-1
5-fluoro-17,18,19,20-tetranor P
GE ₁ carboxamide, N-methanesulfonyl-16
(3-Chlorophenoxy) -15-deoxy-15-fluoro-17,18,19,20-tetranor PGE ₁
Carboxamide, N-methanesulfonyl-16- (3-
Trifluoromethylphenoxy) -15-deoxy-1
5-fluoro-17,18,19,20-tetranor P
GE ₁ carboxamide, N-methanesulfonyl-16
Phenoxy-15-deoxy-15-fluoro-17,
18,19,20- tetranor PGE _{1-carboxamide,} N- methanesulfonyl-17-phenyl-15-deoxy-15-fluoro-18,19,20-trinor PGE _{1-carboxamide.}

11,15-dideoxy-15-fluoro-PGE ₁ methyl ester, 11,15-dideoxy-
15-Fluoro-PGE ₁ ethyl ester, 11,15
-Dideoxy-15-fluoro-PGE ₁ isopropyl ester, 16- (3,5-dichlorophenoxy) -1
1,15-dideoxy-15-fluoro-17,18,
19,20-tetranor PGE ₁ methyl ester, 16
-(3,5-dichlorophenoxy) -11,15-dideoxy-15-fluoro-17,18,19,20-tetranor PGE ₁ ethyl ester, 16- (3,5-dichlorophenoxy) -11,15-dideoxy -15-
Fluoro-17,18,19,20-tetranor PGE
₁ isopropyl ester.

16- (3,4-dichlorophenoxy)-
11,15-dideoxy-15-fluoro-17,1
8,19,20-tetranor PGE ₁ methyl ester,
16- (3,4-dichlorophenoxy) -11,15-
Dideoxy-15-fluoro-17,18,19,20
-Tetranor PGE ₁ ethyl ester, 16- (3,4
-Dichlorophenoxy) -11,15-dideoxy-1
5-fluoro-17,18,19,20-tetranor P
GE ₁ isopropyl ester, 16- (3-chlorophenoxy) -11,15-dideoxy-15-fluoro-
17,18,19,20-tetranor PGE ₁ methyl ester, 16- (3-chlorophenoxy) -11,15
-Dideoxy-15-fluoro-17,18,19,2
0-tetranor PGE ₁ ethyl ester, 16- (3-
(Chlorophenoxy) -11,15-dideoxy-15-
Fluoro-17,18,19,20-tetranor PGE
₁ isopropyl ester.

16- (3-trifluoromethylphenoxy) -11,15-dideoxy-15-fluoro-1
7,18,19,20-tetranor PGE ₁ methyl ester, 16- (3-trifluoromethylphenoxy)-
11,15-dideoxy-15-fluoro-17,1
8,19,20-tetranor PGE ₁ ethyl ester,
16- (3-trifluoromethylphenoxy) -11,
15-dideoxy-15-fluoro-17,18,1
9,20-tetranor PGE ₁ isopropyl ester,
16-phenoxy-11,15-dideoxy-15-fluoro-17,18,19,20-tetranor PGE ₁
Methyl ester, 16-phenoxy-11,15-dideoxy-15-fluoro-17,18,19,20-tetranor PGE ₁ ethyl ester, 16-phenoxy-
11,15-dideoxy-15-fluoro-17,1
8,19,20-tetranor PGE ₁ isopropyl ester.

17-phenyl-11,15-dideoxy-15-fluoro-18,19,20-trinor PGE
₁ methyl ester, 17-phenyl-11,15-dideoxy-15-fluoro-18,19,20-trinor PGE ₁ ethyl ester, 17-phenyl-11,15
-Dideoxy-15-fluoro-18,19,20-trinor PGE ₁ isopropyl ester, 11,15-dideoxy-15-fluoro-13,14-dihydroPG
E ₁ methyl ester, 11,15-dideoxy-15-
Fluoro-13,14-dihydroPGE ₁ ethyl ester, 11,15-dideoxy-15-fluoro-13,
14-dihydro PGE ₁ isopropyl ester.

16- (3,5-dichlorophenoxy)-
11,15-dideoxy-15-fluoro-13,14
-Dihydro-17,18,19,20-tetranor PG
E ₁ methyl ester, 16- (3,5-dichlorophenoxy) -11,15-dideoxy-15-fluoro-1
3,14-dihydro-17,18,19,20-tetranor PGE ₁ ethyl ester, 16- (3,5-dichlorophenoxy) -11,15-dideoxy-15-fluoro-13,14-dihydro-17,18 , 19,20
-Tetranor PGE ₁ isopropyl ester, 16-
(3,4-dichlorophenoxy) -11,15-dideoxy-15-fluoro-13,14-dihydro-17,
18,19,20-tetranor PGE ₁ methyl ester, 16- (3,4-dichlorophenoxy) -11,1
5-dideoxy-15-fluoro-13,14-dihydro-17,18,19,20-tetranor PGE ₁ ethyl ester, 16- (3,4-dichlorophenoxy)-
11,15-dideoxy-15-fluoro-13,14
-Dihydro-17,18,19,20-tetranor PG
E ₁ isopropyl ester, 16- (3-chlorophenoxy) -11,15-dideoxy-15-fluoro-1
3,14-dihydro-17,18,19,20-tetranor PGE ₁ methyl ester, 16- (3-chlorophenoxy) -11,15-dideoxy-15-fluoro-
13,14-dihydro-17,18,19,20-tetranor PGE ₁ ethyl ester, 16- (3-chlorophenoxy) -11,15-dideoxy-15-fluoro-13,14-dihydro-17,18,19 , 20-tetranor PGE ₁ isopropyl ester.

16- (3-trifluoromethylphenoxy) -11,15-dideoxy-15-fluoro-1
3,14-dihydro-17,18,19,20-tetranor PGE ₁ methyl ester, 16- (3-trifluoromethylphenoxy) -11,15-dideoxy-15
-Fluoro-13,14-dihydro-17,18,1
9,20-tetranor PGE ₁ ethyl ester, 16-
(3-trifluoromethylphenoxy) -11,15-
Dideoxy-15-fluoro-13,14-dihydro-
17,18,19,20-tetranor PGE ₁ isopropyl ester, 16-phenoxy-11,15-dideoxy-15-fluoro-13,14-dihydro-17,
18,19,20-tetranor PGE ₁ methyl ester, 16-phenoxy-11,15-dideoxy-15
-Fluoro-13,14-dihydro-17,18,1
9,20-tetranor PGE ₁ ethyl ester, 16-
Phenoxy-11,15-dideoxy-15-fluoro-13,14-dihydro-17,18,19,20-tetranor PGE ₁ isopropyl ester, 17-phenyl-11,15-dideoxy-15-fluoro-13,
14-dihydro-18,19,20-trinor PGE ₁
Methyl ester, 17-phenyl-11,15-dideoxy-15-fluoro-13,14-dihydro-18,
19,20-trinor PGE ₁ ethyl ester, 17-
Phenyl-11,15-dideoxy-15-fluoro-
13,14-dihydro-18,19,20-trinor P
GE ₁ isopropyl ester.

11,15-dideoxy-15-fluoro-3-oxa-17,18,19,20-tetranor P
GE ₁ methyl ester, 11,15-dideoxy-15
-Fluoro-3-oxa-17,18,19,20-tetranor PGE ₁ ethyl ester, 11,15-dideoxy-15-fluoro-3-oxa-17,18,1
9,20-tetranor PGE ₁ isopropyl ester,
16- (3,5-dichlorophenoxy) -11,15-
Dideoxy-15-fluoro-3-oxa-17,1
8,19,20-tetranor PGE ₁ methyl ester,
16- (3,5-dichlorophenoxy) -11,15-
Dideoxy-15-fluoro-3-oxa-17,1
8,19,20-tetranor PGE ₁ ethyl ester,
16- (3,5-dichlorophenoxy) -11,15-
Dideoxy-15-fluoro-3-oxa-17,1
8,19,20-tetranor PGE ₁ isopropyl ester, 16- (3,4-dichlorophenoxy) -11,
15-dideoxy-15-fluoro-3-oxa-1
7,18,19,20-tetranor PGE ₁ methyl ester, 16- (3,4-dichlorophenoxy) -11,
15-dideoxy-15-fluoro-3-oxa-1
7,18,19,20-tetranor PGE ₁ ethyl ester, 16- (3,4-dichlorophenoxy) -11,
15-dideoxy-15-fluoro-3-oxa-1
7,18,19,20-tetranor PGE ₁ isopropyl ester.

16- (3-chlorophenoxy) -11,
15-dideoxy-15-fluoro-3-oxa-1
7,18,19,20-tetranor PGE ₁ methyl ester, 16- (3-chlorophenoxy) -11,15-
Dideoxy-15-fluoro-3-oxa-17,1
8,19,20-tetranor PGE ₁ ethyl ester,
16- (3-chlorophenoxy) -11,15-dideoxy-15-fluoro-3-oxa-17,18,1
9,20-tetranor PGE ₁ isopropyl ester,
16- (3-trifluoromethylphenoxy) -11,
15-dideoxy-15-fluoro-3-oxa-1
7,18,19,20-tetranor PGE ₁ methyl ester, 16- (3-trifluoromethylphenoxy)-
11,15-dideoxy-15-fluoro-3-oxa-17,18,19,20-tetranor PGE ₁ ethyl ester, 16- (3-trifluoromethylphenoxy) -11,15-dideoxy-15-fluoro-3 −
Oxa-17,18,19,20-tetranor PGE ₁
Isopropyl ester.

16-phenoxy-11,15-dideoxy-15-fluoro-3-oxa-17,18,19,
20-tetranor PGE ₁ methyl ester, 16-phenoxy-11,15-dideoxy-15-fluoro-3
-Oxa-17,18,19,20-tetranor PGE
₁ ethyl ester, 16-phenoxy-11,15-dideoxy-15-fluoro-3-oxa-17,18,
19,20-tetranor PGE ₁ isopropyl ester, 17-phenyl-11,15-dideoxy-15-
Fluoro-3-oxa-18,19,20-trinor P
GE ₁ methyl ester, 17-phenyl-11,15-
Dideoxy-15-fluoro-3-oxa-18,1
9,20-trinor PGE ₁ ethyl ester, 17-phenyl-11,15-dideoxy-15-fluoro-3
-Oxa-18,19,20-trinor PGE ₁ isopropyl ester, 11,15-dideoxy-15-fluoro-17,18,19,20-tetranor PGE ₁ .

16- (3,5-dichlorophenoxy)-
11,15-dideoxy-15-fluoro-17,1
8,19,20-tetranor PGE ₁ , 16- (3,4
-Dichlorophenoxy) -11,15-dideoxy-1
5-fluoro-17,18,19,20-tetranor P
GE _1, 16- (3- chlorophenoxy) -11,15
-Dideoxy-15-fluoro-17,18,19,2
0-tetranor PGE ₁ , 16- (3-trifluoromethylphenoxy) -11,15-dideoxy-15-fluoro-17,18,19,20-tetranor PGE
_1, 16-phenoxy -11,15- dideoxy -15
-Fluoro-17,18,19,20-tetranor PG
E _1, 17- phenyl -11,15- dideoxy -15
-Fluoro-18,19,20-trinor PGE ₁ , 1
1,15-dideoxy-15-fluoro-13,14-
Dihydro PGE _1, 16- (3,5- dichlorophenoxy) -11,15- dideoxy-15-fluoro -1
3,14-dihydro-17,18,19,20-tetranor PGE ₁ , 16- (3,4-dichlorophenoxy)-
11,15-dideoxy-15-fluoro-13,14
-Dihydro-17,18,19,20-tetranor PG
E ₁ .

16- (3-chlorophenoxy) -11,
15-dideoxy-15-fluoro-13,14-dihydro-17,18,19,20-tetranor PGE ₁ ,
16- (3-trifluoromethylphenoxy) -11,
15-dideoxy-15-fluoro-13,14-dihydro-17,18,19,20-tetranor PGE ₁ ,
16-phenoxy-11,15-dideoxy-15-fluoro-13,14-dihydro-17,18,19,2
0-tetranor PGE ₁ , 17-phenyl-11,15
-Dideoxy-15-fluoro-13,14-dihydro-18,19,20-trinor PGE ₁ , 11,15-
Dideoxy-15-fluoro-3-oxa-17,1
8,19,20-tetranor PGE ₁ , 16- (3,5
-Dichlorophenoxy) -11,15-dideoxy-1
5-fluoro-3-oxa-17,18,19,20-
Tetranor PGE ₁ , 16- (3,4-dichlorophenoxy) -11,15-dideoxy-15-fluoro-3
-Oxa-17,18,19,20-tetranor PGE
₁ , 16- (3-chlorophenoxy) -11,15-dideoxy-15-fluoro-3-oxa-17,18,
19,20-tetranor PGE ₁ , 16- (3-trifluoromethylphenoxy) -11,15-dideoxy-
15-fluoro-13,14-dihydro-3-oxa-
17, 18, 19, 20-tetranor PGE ₁ .

16-phenoxy-11,15-dideoxy-15-fluoro-13,14-dihydro-3-oxa-17,18,19,20-tetranor PGE ₁ , 1
7-phenyl-11,15-dideoxy-15-fluoro-13,14-dihydro-3-oxa-18,19,
20-trinor PGE ₁ , N-methanesulfonyl-1
1,15-dideoxy-15-fluoro-17,18,
19,20-tetranor PGE ₁ carboxamide, N-
Methanesulfonyl-16- (3,5-dichlorophenoxy) -11,15-dideoxy-15-fluoro-1
7,18,19,20-tetranor PGE ₁ carboxamide, N-methanesulfonyl-16- (3,4-dichlorophenoxy) -11,15-dideoxy-15-fluoro-17,18,19,20-tetranor PGE ₁ Carboxamide.

[0166] N- methanesulfonyl-16- (3-chlorophenoxy) -11,15- dideoxy-15-fluoro-tetranor-PGE _{1-carboxamide,} N- methanesulfonyl-16- (3- trifluoromethylphenoxy) -11,15- dideoxy-15-fluoro-tetranor-PGE _{1-carboxamide,} N- methanesulfonyl -
16-phenoxy-11,15-dideoxy-15-fluoro-17,18,19,20-tetranor PGE ₁
Carboxamide, N-methanesulfonyl-17-phenyl-11,15-dideoxy-15-fluoro-18,
19,20-trinor PGE ₁ carboxamide, 15-
Deoxy-15-fluoro-PGD ₂ methyl ester,
15-Deoxy-15-fluoro-PGD ₂ ethyl ester, 15-deoxy-15-fluoro-PGD ₂ isopropyl ester.

16- (3,5-dichlorophenoxy)-
15-deoxy-15-fluoro-17,18,19,
20-tetranor PGD ₂ methyl ester, 16-
(3,5-dichlorophenoxy) -15-deoxy-1
5-fluoro-17,18,19,20-tetranor P
GD ₂ ethyl ester, 16- (3,5-dichlorophenoxy) -15-deoxy-15-fluoro-17,1
8,19,20-tetranor PGD ₂ isopropyl ester, 16- (3,4-dichlorophenoxy) -15
Deoxy-15-fluoro-17,18,19,20-
Tetranor PGD ₂ methyl ester, 16- (3,4-
Dichlorophenoxy) -15-deoxy-15-fluoro-17,18,19,20-tetranor PGD ₂ ethyl ester, 16- (3,4-dichlorophenoxy)-
15-deoxy-15-fluoro-17,18,19,
20-tetranor PGD ₂ isopropyl ester, 16
-(3-chlorophenoxy) -15-deoxy-15-
Fluoro-17,18,19,20-tetranor PGD
_2- methyl ester, 16- (3-chlorophenoxy)-
15-deoxy-15-fluoro-17,18,19,
20-tetranor PGD ₂ ethyl ester, 16- (3
-Chlorophenoxy) -15-deoxy-15-fluoro-17,18,19,20-tetranor PGD ₂ isopropyl ester.

16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-17,18,
19,20-tetranor PGD ₂ methyl ester, 16
-(3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-17,18,19,20-tetranor PGD ₂ ethyl ester, 16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro -17,18,19,20-tetranor PGD ₂ isopropyl ester, 16-phenoxy-15-deoxy-15-fluoro-17,18,19,20-tetranor PGD ₂ methyl ester, 16-phenoxy-15
-Deoxy-15-fluoro-17,18,19,20
-Tetranor PGD ₂ ethyl ester, 16-phenoxy-15-deoxy-15-fluoro-17,18,1
9,20-tetranor PGD ₂ isopropyl ester.

17-phenyl-15-deoxy-15-
Fluoro-18,19,20-trinor PGD ₂ methyl ester, 17-phenyl-15-deoxy-15-fluoro-18,19,20-trinor PGD ₂ ethyl ester, 17-phenyl-15-deoxy-15-fluoro- 18,19,20-trinor PGD ₂ isopropyl ester, 15-deoxy-15-fluoro-13,
14-dihydro-PGD ₂ methyl ester, 15-deoxy-15-fluoro-13,14-dihydro-PGD ₂ ethyl ester, 15-deoxy-15-fluoro -1
3,14-dihydroPGD ₂ isopropyl ester.

16- (3,5-dichlorophenoxy)-
15-deoxy-15-fluoro-13,14-dihydro-17,18,19,20-tetranor PGD ₂ methyl ester, 16- (3,5-dichlorophenoxy)-
15-deoxy-15-fluoro-13,14-dihydro-17,18,19,20-tetranor PGD ₂ ethyl ester, 16- (3,5-dichlorophenoxy)-
15-deoxy-15-fluoro-13,14-dihydro-17,18,19,20-tetranor PGD ₂ isopropyl ester, 16- (3,4-dichlorophenoxy) -15-deoxy-15-fluoro-13,14 −
Dihydro-17,18,19,20-tetranor PGD
_2- methyl ester, 16- (3,4-dichlorophenoxy) -15-deoxy-15-fluoro-13,14-
Dihydro-17,18,19,20-tetranor PGD
_2- ethyl ester, 16- (3,4-dichlorophenoxy) -15-deoxy-15-fluoro-13,14-
Dihydro-17,18,19,20-tetranor PGD
₂ isopropyl ester.

16- (3-chlorophenoxy) -15-
Deoxy-15-fluoro-13,14-dihydro-1
7,18,19,20-tetranor PGD ₂ methyl ester, 16- (3-chlorophenoxy) -15-deoxy-15-fluoro-13,14-dihydro-17,1
8,19,20-tetranor PGD ₂ ethyl ester,
16- (3-chlorophenoxy) -15-deoxy-1
5-fluoro-13,14-dihydro-17,18,1
9,20-tetranor PGD ₂ isopropyl ester,
16- (3-trifluoromethylphenoxy) -15-
Deoxy-15-fluoro-13,14-dihydro-1
7,18,19,20-tetranor PGD ₂ methyl ester, 16- (3-trifluoromethylphenoxy)-
15-deoxy-15-fluoro-13,14-dihydro-17,18,19,20-tetranor PGD ₂ ethyl ester, 16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-13,14 −
Dihydro-17,18,19,20-tetranor PGD
₂ isopropyl ester.

16-phenoxy-15-deoxy-15
-Fluoro-13,14-dihydro-17,18,1
9,20-tetranor PGD ₂ methyl ester, 16-
Phenoxy-15-deoxy-15-fluoro-13,
14-dihydro-17,18,19,20-tetranor PGD ₂ ethyl ester, 16-phenoxy-15-deoxy-15-fluoro-13,14-dihydro-1
7,18,19,20-tetranor PGD ₂ isopropyl ester, 17-phenyl-15-deoxy-15-
Fluoro-13,14-dihydro-18,19,20-
Trinor PGD ₂ methyl ester, 17-phenyl-1
5-deoxy-15-fluoro-13,14-dihydro-18,19,20-trinor PGD ₂ ethyl ester, 17-phenyl-15-deoxy-15-fluoro-13,14-dihydro-18,19,20- Trinor PGD ₂ isopropyl ester.

15-deoxy-15-fluoro-3-oxa-17,18,19,20-tetranor PGD ₂ methyl ester, 15-deoxy-15-fluoro-3-
Oxa tetranor-PGD ₂
Ethyl ester, 15-deoxy-15-fluoro-3
-Oxa-17,18,19,20-tetranor PGD
_2- isopropyl ester, 16- (3,5-dichlorophenoxy) -15-deoxy-15-fluoro-3-oxa-17,18,19,20-tetranor PGD _2- methyl ester, 16- (3,5-dichlorophenoxy) )
-15-deoxy-15-fluoro-3-oxa-1
7,18,19,20-tetranor PGD ₂ ethyl ester, 16- (3,5-dichlorophenoxy) -15
Deoxy-15-fluoro-3-oxa-17,18,
19,20-tetranor PGD ₂ isopropyl ester.

16- (3,4-dichlorophenoxy)-
15-deoxy-15-fluoro-3-oxa-17,
18,19,20-tetranor PGD ₂ methyl ester, 16- (3,4-dichlorophenoxy) -15-deoxy-15-fluoro-3-oxa-17,18,1
9,20-tetranor PGD ₂ ethyl ester, 16-
(3,4-dichlorophenoxy) -15-deoxy-1
5-fluoro-3-oxa-17,18,19,20-
Tetranor PGD ₂ isopropyl ester, 16- (3
-Chlorophenoxy) -15-deoxy-15-fluoro-3-oxa-17,18,19,20-tetranor PGD ₂ methyl ester, 16- (3-chlorophenoxy) -15-deoxy-15-fluoro-3- Oxa
17,18,19,20-tetranor PGD ₂ ethyl ester, 16- (3-chlorophenoxy) -15-deoxy-15-fluoro-3-oxa-17,18,1
9,20-tetranor PGD ₂ isopropyl ester.

16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-3-oxa-
17,18,19,20-tetranor PGD ₂ methyl ester, 16- (3-trifluoromethylphenoxy)
-15-deoxy-15-fluoro-3-oxa-1
7,18,19,20-tetranor PGD ₂ ethyl ester, 16- (3-trifluoromethylphenoxy)-
15-deoxy-15-fluoro-3-oxa-17,
18,19,20-tetranor PGD ₂ isopropyl ester, 16-phenoxy-15-deoxy-15-fluoro-3-oxa-17,18,19,20-tetranor PGD ₂ methyl ester, 16-phenoxy-15
-Deoxy-15-fluoro-3-oxa-17,1
8,19,20-tetranor PGD ₂ ethyl ester,
16-phenoxy-15-deoxy-15-fluoro-
3-oxa-17,18,19,20-tetranor PG
D ₂ isopropyl ester.

17-phenyl-15-deoxy-15-
Fluoro-3-oxa-18,19,20-trinor P
GD ₂ methyl ester, 17-phenyl-15-deoxy-15-fluoro-3-oxa-18,19,20-
Trinor PGD ₂ ethyl ester, 17-phenyl-1
5-deoxy-15-fluoro-3-oxa-18,1
9,20-trinor PGD ₂ isopropyl ester, 1
5-deoxy-15-fluoro-9-pivaloyl PGD
_2- methyl ester, 15-deoxy-15-fluoro-
9-pivaloyl PGD ₂ ethyl ester, 15-deoxy-15-fluoro-9-pivaloyl PGD ₂ isopropyl ester, 16- (3,5-dichlorophenoxy)
-15-deoxy-15-fluoro-9-pivaloyl-
17,18,19,20-tetranor PGD ₂ methyl ester, 16- (3,5-dichlorophenoxy) -15
-Deoxy-15-fluoro-9-pivaloyl-17,
18,19,20-tetranor PGD ₂ ethyl ester, 16- (3,5-dichlorophenoxy) -15-deoxy-15-fluoro-9-pivaloyl-17,1
8,19,20-tetranor PGD ₂ isopropyl ester.

16- (3,4-dichlorophenoxy)-
15-deoxy-15-fluoro-9-pivaloyl-1
7,18,19,20-tetranor PGD ₂ methyl ester, 16- (3,4-dichlorophenoxy) -15
Deoxy-15-fluoro-9-pivaloyl-17,1
8,19,20-tetranor PGD ₂ ethyl ester,
16- (3,4-dichlorophenoxy) -15-deoxy-15-fluoro-9-pivaloyl-17,18,1
9,20-tetranor PGD ₂ isopropyl ester,
16- (3-chlorophenoxy) -15-deoxy-1
5-fluoro-9-pivaloyl-17,18,19,2
0-tetranor PGD ₂ methyl ester, 16- (3-
Chlorophenoxy) -15-deoxy-15-fluoro-9-pivaloyl tetranor-PGD ₂ ethyl ester, 16- (3-chlorophenoxy) -15-deoxy-15-fluoro-9-pivaloyl -17,18,19,20-tetranor PGD ₂ isopropyl ester.

16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-9-pivaloyl-17,18,19,20-tetranor PGD ₂ methyl ester, 16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-9-pivaloyl-17,18,19,20-tetranor PGD ₂ ethyl ester, 16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-9-pivaloyl- 17,18,19,20-tetranor PGD ₂ isopropyl ester, 16-phenoxy-15-deoxy-15-fluoro-9-pivaloyl-17,18,1
9,20-tetranor PGD ₂ methyl ester, 16-
Phenoxy-15-deoxy-15-fluoro-9-pivaloyl-17,18,19,20-tetranor PGD
_2- ethyl ester, 16-phenoxy-15-deoxy-15-fluoro-9-pivaloyl-17,18,1
9,20-tetranor PGD ₂ isopropyl ester.

17-phenyl-15-deoxy-15-
Fluoro-9-pivaloyl-18,19,20-trinor PGD ₂ methyl ester, 17-phenyl-15-deoxy-15-fluoro-9-pivaloyl-18,1
9,20-trinor PGD ₂ ethyl ester, 17-phenyl-15-deoxy-15-fluoro-9-pivaloyl-18,19,20-trinor PGD ₂ isopropyl ester, 15-deoxy-15-fluoro-PGD
₂ 1,9-lactone, 16- (3,5-dichlorophenoxy) -15-deoxy-15-fluoro -17,1
8,19,20-tetranor PGD ₂ 1,9-lactone, 16- (3,4-dichlorophenoxy) -15-deoxy-15-fluoro-17,18,19,20-tetranor PGD ₂ 1,9-lactone .

16- (3-chlorophenoxy) -15-
Deoxy-15-fluoro-17,18,19,20-
Tetranor PGD ₂ 1,9-lactone, 16- (3-trifluoromethylphenoxy) -15-deoxy -15
-Fluoro-17,18,19,20-tetranor PG
D ₂ 1,9-lactone, 16-phenoxy-15-deoxy-15-fluoro-17,18,19,20-tetranor PGD ₂ 1,9-lactone, 17-phenyl-1
5-deoxy-15-fluoro-18,19,20-trinor PGD ₂ 1,9-lactone, 15-deoxy-1
5-fluoro-17,18,19,20-tetranor P
GD ₂ , 16- (3,5-dichlorophenoxy) -15
-Deoxy-15-fluoro-17,18,19,20
- tetranor PGD _2, 16- (3,4- dichlorophenoxy) -15-deoxy-15-fluoro -17,1
8,19,20-tetranor PGD ₂ , 16- (3-chlorophenoxy) -15-deoxy-15-fluoro-
17, 18, 19, 20-tetranor PGD ₂ , 16-
(3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-tetranor-PGD _2,

16-phenoxy-15-deoxy-15
-Fluoro-17,18,19,20-tetranor PG
D _2, 17-phenyl-15-deoxy-15-fluoro-18,19,20-trinor PGD _2, 15-deoxy-15-fluoro-13,14-dihydro-PGD
_2, 16- (3,5-dichlorophenoxy) -15-deoxy-15-fluoro-13,14-dihydro-1
7,18,19,20-tetranor PGD ₂ , 16-
(3,4-dichlorophenoxy) -15-deoxy-1
5-fluoro-13,14-dihydro-17,18,1
9,20-tetranor PGD ₂ , 16- (3-chlorophenoxy) -15-deoxy-15-fluoro-13,
14-dihydro-17,18,19,20-tetranor PGD ₂ , 16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-13,14-
Dihydro-17,18,19,20-tetranor PGD
_2, 16-phenoxy-15-deoxy-15-fluoro-13,14-dihydro-17,18,19,20
Tetranor PGD ₂ , 17-phenyl-15-deoxy-15-fluoro-13,14-dihydro-18,1
9,20-trinor PGD ₂ .

15-deoxy-15-fluoro-3-oxa-17,18,19,20-tetranor PGD ₂ ,
16- (3,5-dichlorophenoxy) -15-deoxy-15-fluoro-3-oxa-17,18,19,
20-tetranor PGD ₂ , 16- (3,4-dichlorophenoxy) -15-deoxy-15-fluoro-3-
Oxa-17,18,19,20-tetranor PGD
₂ , 16- (3-chlorophenoxy) -15-deoxy-15-fluoro-3-oxa-17,18,19,2
0-tetranor PGD ₂ , 16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-
13,14-dihydro-3-oxa-17,18,1
9,20-tetranor PGD ₂ .

16-phenoxy-15-deoxy-15
-Fluoro-13,14-dihydro-3-oxa-1
7,18,19,20-tetranor PGD ₂ , 17-phenyl-15-deoxy-15-fluoro-13,14
-Dihydro-3-oxa-18,19,20-trinor PGD ₂ , N-methanesulfonyl-15-deoxy-1
5-fluoro-17,18,19,20-tetranor P
GD ₂ carboxamide, N-methanesulfonyl-16-
(3,5-dichlorophenoxy) -15-deoxy-1
5-fluoro-17,18,19,20-tetranor P
GD ₂ carboxamide, N-methanesulfonyl-16-
(3,4-dichlorophenoxy) -15-deoxy-1
5-fluoro-17,18,19,20-tetranor P
GD ₂ carboxamide, N-methanesulfonyl-16-
(3-chlorophenoxy) -15-deoxy-15-fluoro-17,18,19,20-tetranor PGD ₂
Carboxamide, N-methanesulfonyl-16- (3-
Trifluoromethylphenoxy) -15-deoxy-1
5-fluoro-17,18,19,20-tetranor P
GD ₂ carboxamide.

N-methanesulfonyl-16-phenoxy-15-deoxy-15-fluoro-17,18,1
9,20-tetranor PGD ₂ carboxamide, N-methanesulfonyl-17-phenyl-15-deoxy-1
5-fluoro-18,19,20-trinor PGD ₂ carboxamide, 9,15-dideoxy-15-fluoro-PGD ₁ methyl ester, 9,15-dideoxy-1
5-fluoro-PGD ₁ ethyl ester, 9,15-dideoxy-15-fluoro-PGD ₁ isopropyl ester, 16- (3,5-dichlorophenoxy) -9,1
5-dideoxy-15-fluoro-17,18,19,
20-tetranor PGD ₁ methyl ester, 16-
(3,5-dichlorophenoxy) -9,15-dideoxy-15-fluoro-17,18,19,20-tetranor PGD ₁ ethyl ester, 16- (3,5-dichlorophenoxy) -9,15-dideoxy- 15-Fluoro-17,18,19,20-tetranor PGD ₁ isopropyl ester.

16- (3,4-dichlorophenoxy)-
9,15-dideoxy-15-fluoro-17,18,
19,20-tetranor PGD ₁ methyl ester, 16
-(3,4-dichlorophenoxy) -9,15-dideoxy-15-fluoro-17,18,19,20-tetranor PGD ₁ ethyl ester, 16- (3,4-dichlorophenoxy) -9,15-dideoxy -15-fluoro-17,18,19,20-tetranor PGD ₁ isopropyl ester, 16- (3-chlorophenoxy)
-9,15-Dideoxy-15-fluoro-17,1
8,19,20-tetranor PGD ₁ methyl ester,
16- (3-chlorophenoxy) -9,15-dideoxy-15-fluoro-17,18,19,20-tetranor PGD ₁ ethyl ester, 16- (3-chlorophenoxy) -9,15-dideoxy-15- Fluoro-1
7,18,19,20-tetranor PGD ₁ isopropyl ester.

16- (3-trifluoromethylphenoxy) -9,15-dideoxy-15-fluoro-17,
18,19,20-tetranor PGD ₁ methyl ester, 16- (3-trifluoromethylphenoxy)-
9,15-dideoxy-15-fluoro-17,18,
19,20-tetranor PGD ₁ ethyl ester, 16
-(3-trifluoromethylphenoxy) -9,15-
Dideoxy-15-fluoro-17,18,19,20
-Tetranor PGD ₁ isopropyl ester, 16-phenoxy-9,15-dideoxy-15-fluoro-1
7,18,19,20-tetranor PGD ₁ methyl ester, 16-phenoxy-9,15-dideoxy-15
-Fluoro-17,18,19,20-tetranor PG
D ₁ ethyl ester, 16-phenoxy-9,15-dideoxy-15-fluoro-17,18,19,20-
Tetranor PGD ₁ isopropyl ester.

17-phenyl-9,15-dideoxy-
15-Fluoro-18,19,20-trinor PGD ₁
Methyl ester, 17-phenyl-9,15-dideoxy-15-fluoro-18,19,20-trinor PG
D ₁ ethyl ester, 17-phenyl-9,15-dideoxy-15-fluoro-18,19,20-trinor PGD ₁ isopropyl ester, 9,15-dideoxy-15-fluoro-13,14-dihydro PGD ₁ methyl ester , 9,15-Dideoxy-15-fluoro-
13,14-dihydroPGD ₁ ethyl ester, 9.1
5-Dideoxy-15-fluoro-13,14-dihydroPGD ₁ isopropyl ester.

16- (3,5-dichlorophenoxy)-
9,15-dideoxy-15-fluoro-13,14-
Dihydro-17,18,19,20-tetranor PGD
₁ methyl ester, 16- (3,5-dichlorophenoxy) -9,15-dideoxy-15-fluoro-13,
14-dihydro-17,18,19,20-tetranor PGD ₁ ethyl ester, 16- (3,5-dichlorophenoxy) -9,15-dideoxy-15-fluoro-
13,14-dihydro-17,18,19,20-tetranor PGD ₁ isopropyl ester, 16- (3,4
-Dichlorophenoxy) -9,15-dideoxy-15
-Fluoro-13,14-dihydro-17,18,1
9,20-tetranor PGD ₁ methyl ester, 16-
(3,4-dichlorophenoxy) -9,15-dideoxy-15-fluoro-13,14-dihydro-17,1
8,19,20-tetranor PGD ₁ ethyl ester,
16- (3,4-dichlorophenoxy) -9,15-dideoxy-15-fluoro-13,14-dihydro-1
7,18,19,20-tetranor PGD ₁ isopropyl ester, 16- (3-chlorophenoxy) -9,1
5-dideoxy-15-fluoro-13,14-dihydro-17,18,19,20-tetranor PGD ₁ methyl ester, 16- (3-chlorophenoxy) -9,1
5-dideoxy-15-fluoro-13,14-dihydro-17,18,19,20-tetranor PGD ₁ ethyl ester, 16- (3-chlorophenoxy) -9,1
5-Dideoxy-15-fluoro-13,14-dihydro-17,18,19,20-tetranor PGD ₁ isopropyl ester.

16- (3-trifluoromethylphenoxy) -9,15-dideoxy-15-fluoro-13,
14-dihydro-17,18,19,20-tetranor PGD ₁ methyl ester, 16- (3-trifluoromethylphenoxy) -9,15-dideoxy-15-fluoro-13,14-dihydro-17,18,19 , 20
-Tetranor PGD ₁ ethyl ester, 16- (3-trifluoromethylphenoxy) -9,15-dideoxy-15-fluoro-13,14-dihydro-17,1
8,19,20-tetranor PGD ₁ isopropyl ester, 16-phenoxy-9,15-dideoxy-15
-Fluoro-13,14-dihydro-17,18,1
9,20-tetranor PGD ₁ methyl ester, 16-
Phenoxy-9,15-dideoxy-15-fluoro-
13,14-dihydro-17,18,19,20-tetranor PGD ₁ ethyl ester, 16-phenoxy-
9,15-dideoxy-15-fluoro-13,14-
Dihydro-17,18,19,20-tetranor PGD
₁ isopropyl ester.

17-phenyl-9,15-dideoxy-
15-fluoro-13,14-dihydro-18,19,
20-trinor PGD ₁ methyl ester, 17-phenyl-9,15-dideoxy-15-fluoro-13,1
4-dihydro-18,19,20-trinor PGD ₁ ethyl ester, 17-phenyl-9,15-dideoxy-15-fluoro-13,14-dihydro-18,1
9,20-trinor PGD ₁ isopropyl ester,
9,15-dideoxy-15-fluoro-3-oxa-
17,18,19,20-tetranor PGD ₁ methyl ester, 9,15-dideoxy-15-fluoro-3-
Oxa-17,18,19,20-tetranor PGD ₁
Ethyl ester, 9,15-dideoxy-15-fluoro-3-oxa-17,18,19,20-tetranor PGD ₁ isopropyl ester.

16- (3,5-dichlorophenoxy)-
9,15-dideoxy-15-fluoro-3-oxa-
17,18,19,20-tetranor PGD ₁ methyl ester, 16- (3,5-dichlorophenoxy) -9,
15-dideoxy-15-fluoro-3-oxa-1
7,18,19,20-tetranor PGD ₁ ethyl ester, 16- (3,5-dichlorophenoxy) -9,1
5-dideoxy-15-fluoro-3-oxa-17,
18,19,20-tetranor PGD ₁ isopropyl ester, 16- (3,4-dichlorophenoxy) -9,
15-dideoxy-15-fluoro-3-oxa-1
7,18,19,20-tetranor PGD ₁ methyl ester, 16- (3,4-dichlorophenoxy) -9,1
5-dideoxy-15-fluoro-3-oxa-17,
18,19,20-tetranor PGD ₁ ethyl ester, 16- (3,4-dichlorophenoxy) -9,15
-Dideoxy-15-fluoro-3-oxa-17,1
8,19,20-tetranor PGD ₁ isopropyl ester.

16- (3-chlorophenoxy) -9,1
5-dideoxy-15-fluoro-3-oxa-17,
18,19,20-tetranor PGD ₁ methyl ester, 16- (3-chlorophenoxy) -9,15-dideoxy-15-fluoro-3-oxa-17,18,1
9,20-tetranor PGD ₁ ethyl ester, 16-
(3-chlorophenoxy) -9,15-dideoxy-1
5-fluoro-3-oxa-17,18,19,20-
Tetranor PGD ₁ isopropyl ester, 16- (3
-Trifluoromethylphenoxy) -9,15-dideoxy-15-fluoro-3-oxa-17,18,1
9,20-tetranor PGD ₁ methyl ester, 16-
(3-trifluoromethylphenoxy) -9,15-dideoxy-15-fluoro-3-oxa-17,18,
19,20-tetranor PGD ₁ ethyl ester, 16
-(3-trifluoromethylphenoxy) -9,15-
Dideoxy-15-fluoro-3-oxa-17,1
8,19,20-tetranorprostagland D ₁ isopropyl ester.

16-phenoxy-9,15-dideoxy-15-fluoro-3-oxa-17,18,19,2
0-tetranor PGD ₁ methyl ester, 16-phenoxy-9,15-dideoxy-15-fluoro-3-oxa-17,18,19,20-tetranor PGD ₁ ethyl ester, 16-phenoxy-9,15-dideoxy- 15-fluoro-3-oxa-17,18,19,
20-tetranor PGD ₁ isopropyl ester, 17
-Phenyl-9,15-dideoxy-15-fluoro-
3-oxa-18,19,20-trinor PGD ₁ methyl ester, 17-phenyl-9,15-dideoxy-
15-Fluoro-3-oxa-18,19,20-trinor PGD ₁ ethyl ester, 17-phenyl-9,1
5-dideoxy-15-fluoro-3-oxa-18,
19,20-trinor PGD ₁ isopropyl ester,
9,15-dideoxy-15-fluoro-17,18,
19,20-tetranor PGD ₁ .

16- (3,5-dichlorophenoxy)-
9,15-dideoxy-15-fluoro-17,18,
19,20- tetranor PGD _1, 16- (3,4-dichlorophenoxy) -9,15- dideoxy-15-fluoro-tetranor-PGD
_1, 16- (3-chlorophenoxy) -9,15- dideoxy-15-fluoro-tetranor-PGD _1, 16- (3-trifluoromethylphenoxy) -9,15- dideoxy - 15-fluoro-
17,18,19,20- tetranor PGD _1, 16-
Phenoxy-9,15-dideoxy-15-fluoro-
17,18,19,20- tetranor PGD _1, 17-
Phenyl-9,15-dideoxy-15-fluoro-1
8,19,20-trinor PGD ₁ , 9,15-dideoxy-15-fluoro-13,14-dihydro PGD
₁ .

16- (3,5-dichlorophenoxy)-
9,15-dideoxy-15-fluoro-13,14-
Dihydro-17,18,19,20-tetranor PGD
₁ , 16- (3,4-dichlorophenoxy) -9,15
-Dideoxy-15-fluoro-13,14-dihydro-17,18,19,20-tetranor PGD ₁ , 16
-(3-chlorophenoxy) -9,15-dideoxy-
15-fluoro-13,14-dihydro-17,18,
19,20-tetranor PGD ₁ , 16- (3-trifluoromethylphenoxy) -9,15-dideoxy-1
5-fluoro-13,14-dihydro-17,18,1
9,20-tetranor PGD ₁ , 16-phenoxy-
9,15-dideoxy-15-fluoro-13,14-
Dihydro-17,18,19,20-tetranor PGD
_1, 17-phenyl -9,15- dideoxy-15-fluoro-13,14-dihydro-18,19,20-trinor PGD _1, 9,15- dideoxy-15-fluoro-3-oxa -17,18, 19,20-tetranor PGD ₁ .

16- (3,5-dichlorophenoxy)-
9,15-dideoxy-15-fluoro-3-oxa-
17,18,19,20- tetranor PGD _1, 16-
(3,4-dichlorophenoxy) -9,15-dideoxy-15-fluoro-3-oxa-17,18,19,
20- tetranor PGD _1, 16- (3- chlorophenoxy) -9,15- dideoxy-15-fluoro-3-
Oxa-17,18,19,20-tetranor PGD
₁ , 16- (3-trifluoromethylphenoxy)-
9,15-dideoxy-15-fluoro-13,14-
Dihydro-3-oxa-17,18,19,20 tetranor PGD _1, 16- phenoxy -9,15- dideoxy-15-fluoro-13,14-dihydro-3-oxa-17,18,19,20 Tetranor PGD ₁ ,
17-phenyl-9,15-dideoxy-15-fluoro-13,14-dihydro-3-oxa-18,19,
20-trinor PGD ₁ , N-methanesulfonyl-9,
15-dideoxy-15-fluoro-17,18,1
9,20-tetranor PGD ₁ carboxamide.

N-methanesulfonyl-16- (3,5-
Dichlorophenoxy) -9,15-dideoxy-15-
Fluoro-17,18,19,20-tetranor PGD
_{1-carboxamide,} N- methanesulfonyl-16-
(3,4-dichlorophenoxy) -9,15- dideoxy-15-fluoro-tetranor-PGD _{1-carboxamide,} N- methanesulfonyl -
16- (3-chlorophenoxy) -9,15- dideoxy-15-fluoro-tetranor-PGD _{1-carboxamide,} N- methanesulfonyl -
16- (3-trifluoromethylphenoxy) -9,1
5-dideoxy-15-fluoro-17,18,19,
20- tetranor PGD _{1-carboxamide,} N- methanesulfonyl-16-phenoxy -9,15- dideoxy-15-fluoro-tetranor-PGD _{1-carboxamide,} N- methanesulfonyl -1
7-phenyl-9,15-dideoxy-15-fluoro-18,19,20-trinor PGD ₁ carboxamide.

15-Deoxy-15-fluoro-PGD
₁ methyl ester, 15-deoxy-15-fluoro-
PGD ₁ ethyl ester, 15-deoxy-15-fluoro -PGD ₁ isopropyl ester, 16- (3,5
-Dichlorophenoxy) -15-deoxy-15-fluoro-17,18,19,20-tetranor PGD ₁ methyl ester, 16- (3,5-dichlorophenoxy)
-15-deoxy-15-fluoro-17,18,1
9,20-tetranor PGD ₁ ethyl ester, 16-
(3,5-dichlorophenoxy) -15-deoxy-1
5-fluoro-17,18,19,20-tetranor P
GD ₁ isopropyl ester, 16- (3,4-dichlorophenoxy) -15-deoxy-15-fluoro-1
7,18,19,20-tetranor PGD ₁ methyl ester, 16- (3,4-dichlorophenoxy) -15
Deoxy-15-fluoro-17,18,19,20-
Tetranor PGD ₁ ethyl ester, 16- (3,4-
Dichlorophenoxy) -15-deoxy-15-fluoro-17,18,19,20-tetranor PGD ₁ isopropyl ester.

16- (3-chlorophenoxy) -15-
Deoxy-15-fluoro-17,18,19,20-
Tetranor PGD ₁ methyl ester, 16- (3-chlorophenoxy) -15-deoxy-15-fluoro-1
7,18,19,20-tetranor PGD ₁ ethyl ester, 16- (3-chlorophenoxy) -15-deoxy-15-fluoro-17,18,19,20-tetranor PGD ₁ isopropyl ester, 16- (3- (Trifluoromethylphenoxy) -15-deoxy-15-
Fluoro-17,18,19,20-tetranor PGD
₁ methyl ester, 16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-17,
18,19,20-tetranor PGD ₁ ethyl ester, 16- (3-trifluoromethylphenoxy) -1
5-deoxy-15-fluoro-17,18,19,2
0-tetranor PGD ₁ isopropyl ester.

16-phenoxy-15-deoxy-15
-Fluoro-17,18,19,20-tetranor PG
D ₁ methyl ester, 16-phenoxy-15-deoxy-15-fluoro-17,18,19,20-tetranor PGD ₁ ethyl ester, 16-phenoxy-15
-Deoxy-15-fluoro-17,18,19,20
-Tetranor PGD ₁ isopropyl ester, 17-phenyl-15-deoxy-15-fluoro-18,1
9,20-trinor PGD ₁ methyl ester, 17-phenyl-15-deoxy-15-fluoro-18,1
9,20-trinor PGD ₁ ethyl ester, 17-phenyl-15-deoxy-15-fluoro-18,1
9,20-trinor PGD ₁ isopropyl ester, 1
5-deoxy-15-fluoro-13,14-dihydroPGD ₁ methyl ester, 15-deoxy-15-fluoro-13,14-dihydroPGD ₁ ethyl ester,
15-Deoxy-15-fluoro-13,14-dihydroPGD ₁ isopropyl ester.

16- (3,5-dichlorophenoxy)-
15-deoxy-15-fluoro-13,14-dihydro-17,18,19,20-tetranor PGD ₁ methyl ester, 16- (3,5-dichlorophenoxy)-
15-deoxy-15-fluoro-13,14-dihydro-17,18,19,20-tetranor PGD ₁ ethyl ester, 16- (3,5-dichlorophenoxy)-
15-deoxy-15-fluoro-13,14-dihydro-17,18,19,20-tetranor PGD ₁ isopropyl ester, 16- (3,4-dichlorophenoxy) -15-deoxy-15-fluoro-13,14 −
Dihydro-17,18,19,20-tetranor PGD
_1- methyl ester, 16- (3,4-dichlorophenoxy) -15-deoxy-15-fluoro-13,14-
Dihydro-17,18,19,20-tetranor PGD
₁ ethyl ester, 16- (3,4-dichlorophenoxy) -15-deoxy-15-fluoro-13,14-
Dihydro-17,18,19,20-tetranor PGD
₁ isopropyl ester.

16- (3-chlorophenoxy) -15-
Deoxy-15-fluoro-13,14-dihydro-1
7,18,19,20-tetranor PGD ₁ methyl ester, 16- (3-chlorophenoxy) -15-deoxy-15-fluoro-13,14-dihydro-17,1
8,19,20-tetranor PGD ₁ ethyl ester,
16- (3-chlorophenoxy) -15-deoxy-1
5-fluoro-13,14-dihydro-17,18,1
9,20-tetranor PGD ₁ isopropyl ester,
16- (3-trifluoromethylphenoxy) -15-
Deoxy-15-fluoro-13,14-dihydro-1
7,18,19,20-tetranor PGD ₁ methyl ester, 16- (3-trifluoromethylphenoxy)-
15-deoxy-15-fluoro-13,14-dihydro-17,18,19,20-tetranor PGD ₁ ethyl ester, 16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-13,14 −
Dihydro-17,18,19,20-tetranor PGD
₁ isopropyl ester.

16-phenoxy-15-deoxy-15
-Fluoro-13,14-dihydro-17,18,1
9,20-tetranor PGD ₁ methyl ester, 16-
Phenoxy-15-deoxy-15-fluoro-13,
14-dihydro-17,18,19,20-tetranor PGD ₁ ethyl ester, 16-phenoxy-15-deoxy-15-fluoro-13,14-dihydro-1
7,18,19,20-tetranor PGD ₁ isopropyl ester, 17-phenyl-15-deoxy-15-
Fluoro-13,14-dihydro-18,19,20-
Trinor PGD ₁ methyl ester, 17-phenyl-1
5-deoxy-15-fluoro-13,14-dihydro-18,19,20-trinor PGD ₁ ethyl ester, 17-phenyl-15-deoxy-15-fluoro-13,14-dihydro-18,19,20- Trinor PGD ₁ isopropyl ester.

15-deoxy-15-fluoro-3-oxa-17,18,19,20-tetranor PGD ₁ methyl ester, 15-deoxy-15-fluoro-3-
Oxa-17,18,19,20-tetranor PGD ₁
Ethyl ester, 15-deoxy-15-fluoro-3
-Oxa-17,18,19,20-tetranor PGD
_1- isopropyl ester, 16- (3,5-dichlorophenoxy) -15-deoxy-15-fluoro-3-oxa-17,18,19,20-tetranor PGD ₁ methyl ester, 16- (3,5-dichlorophenoxy) )
-15-deoxy-15-fluoro-3-oxa-1
7,18,19,20-tetranor PGD ₁ ethyl ester, 16- (3,5-dichlorophenoxy) -15
Deoxy-15-fluoro-3-oxa-17,18,
19,20-tetranor PGD ₁ isopropyl ester, 16- (3,4-dichlorophenoxy) -15-deoxy-15-fluoro-3-oxa-17,18,1
9,20-tetranor PGD ₁ methyl ester, 16-
(3,4-dichlorophenoxy) -15-deoxy-1
5-fluoro-3-oxa-17,18,19,20-
Tetranor PGD ₁ ethyl ester, 16- (3,4-
Dichlorophenoxy) -15-deoxy-15-fluoro-3-oxa-17,18,19,20-tetranor PGD ₁ isopropyl ester.

16- (3-chlorophenoxy) -15-
Deoxy-15-fluoro-3-oxa-17,18,
19,20-tetranor PGD ₁ methyl ester, 16
-(3-chlorophenoxy) -15-deoxy-15-
Fluoro-3-oxa-17,18,19,20-tetranor PGD ₁ ethyl ester, 16- (3-chlorophenoxy) -15-deoxy-15-fluoro-3-oxa-17,18,19,20-tetranor PGD ₁ isopropyl ester.

16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-3-oxa-
17,18,19,20-tetranor PGD ₁ methyl ester, 16- (3-trifluoromethylphenoxy)
-15-deoxy-15-fluoro-3-oxa-1
7,18,19,20-tetranor PGD ₁ ethyl ester, 16- (3-trifluoromethylphenoxy)-
15-deoxy-15-fluoro-3-oxa-17,
18,19,20-tetranor PGD ₁ isopropyl ester, 16-phenoxy-15-deoxy-15-fluoro-3-oxa-17,18,19,20-tetranor PGD ₁ methyl ester, 16-phenoxy-15
-Deoxy-15-fluoro-3-oxa-17,1
8,19,20-tetranor PGD ₁ ethyl ester,
16-phenoxy-15-deoxy-15-fluoro-
3-oxa-17,18,19,20-tetranor PG
D ₁ isopropyl ester.

17-phenyl-15-deoxy-15-
Fluoro-3-oxa-18,19,20-trinor P
GD ₁ methyl ester, 17-phenyl-15-deoxy-15-fluoro-3-oxa-18,19,20-
Trinor PGD ₁ ethyl ester, 17-phenyl-1
5-deoxy-15-fluoro-3-oxa-18,1
9,20-trinor PGD ₁ isopropyl ester, 1
5-deoxy-15-fluoro-9-pivaloyl PGD
₁ methyl ester, 15-deoxy-15-fluoro-
9-pivaloyl PGD ₁ ethyl ester, 15-deoxy-15-fluoro-9-pivaloyl PGD ₁ isopropyl ester, 16- (3,5-dichlorophenoxy)
-15-deoxy-15-fluoro-9-pivaloyl-
17,18,19,20-tetranor PGD ₁ methyl ester, 16- (3,5-dichlorophenoxy) -15
-Deoxy-15-fluoro-9-pivaloyl-17,
18,19,20-tetranor PGD ₁ ethyl ester, 16- (3,5-dichlorophenoxy) -15-deoxy-15-fluoro-9-pivaloyl-17,1
8,19,20-tetranor PGD ₁ isopropyl ester.

16- (3,4-dichlorophenoxy)-
15-deoxy-15-fluoro-9-pivaloyl-1
7,18,19,20-tetranor PGD ₁ methyl ester, 16- (3,4-dichlorophenoxy) -15
Deoxy-15-fluoro-9-pivaloyl-17,1
8,19,20-tetranor PGD ₁ ethyl ester,
16- (3,4-dichlorophenoxy) -15-deoxy-15-fluoro-9-pivaloyl-17,18,1
9,20-tetranor PGD ₁ isopropyl ester,
16- (3-chlorophenoxy) -15-deoxy-1
5-fluoro-9-pivaloyl-17,18,19,2
0-tetranor PGD ₁ methyl ester, 16- (3-
Chlorophenoxy) -15-deoxy-15-fluoro-9-pivaloyl-17,18,19,20-tetranor PGD ₁ ethyl ester, 16- (3-chlorophenoxy) -15-deoxy-15-fluoro-9-pivaloyl -17,18,19,20-tetranor PGD ₁ isopropyl ester.

16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-9-pivaloyl-17,18,19,20-tetranor PGD ₁ methyl ester, 16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-9-pivaloyl-17,18,19,20-tetranor PGD ₁ ethyl ester, 16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-9-pivaloyl- 17,18,19,20-tetranor PGD ₁ isopropyl ester, 16-phenoxy-15-deoxy-15-fluoro-9-pivaloyl-17,18,1
9,20-tetranor PGD ₁ methyl ester, 16-
Phenoxy-15-deoxy-15-fluoro-9-pivaloyl-17,18,19,20-tetranor PGD
₁ ethyl ester, 16-phenoxy-15-deoxy-15-fluoro-9-pivaloyl-17,18,1
9,20-tetranor PGD ₁ isopropyl ester.

17-phenyl-15-deoxy-15-
Fluoro-9-pivaloyl-18,19,20-trinor PGD ₁ methyl ester, 17-phenyl-15-deoxy-15-fluoro-9-pivaloyl-18,1
9,20-trinor PGD ₁ ethyl ester, 17-phenyl-15-deoxy-15-fluoro-9-pivaloyl-18,19,20-trinor PGD ₁ isopropyl ester, 15-deoxy-15-fluoro PGD ₁
1,9-lactone, 16- (3,5-dichlorophenoxy) -15-deoxy-15-fluoro-17,18,
19,20-tetranor PGD _{11, 9} -lactone, 1
6- (3,4-dichlorophenoxy) -15-deoxy-15-fluoro-17,18,19,20-tetranor PGD _{11, 9} -lactone.

16- (3-chlorophenoxy) -15-
Deoxy-15-fluoro-17,18,19,20-
Tetranor PGD ₁ 1,9-lactone, 16- (3-trifluoromethylphenoxy) -15-deoxy-15
-Fluoro-17,18,19,20-tetranor PG
D ₁ 1,9-lactone, 16-phenoxy-15-deoxy-15-fluoro-tetranor-PGD ₁ 1,9-lactone, 17-phenyl -1
5-deoxy-15-fluoro-18,19,20-trinor PGD _{11, 9} -lactone.

15-deoxy-15-fluoro-17,
18, 19, 20-tetranor PGD ₁ , 16- (3,
5-Dichlorophenoxy) -15-deoxy-15-fluoro-17,18,19,20-tetranor PGD
_1, 16- (3,4-dichlorophenoxy) -15-deoxy-15-fluoro-tetranor-PGD _1, 16- (3- chlorophenoxy) -
15-deoxy-15-fluoro-17,18,19,
20-tetranor PGD ₁ , 16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-17,18,19,20-tetranor PGD ₁ , 16
-Phenoxy-15-deoxy-15-fluoro-1
7,18,19,20-tetranor PGD ₁ , 17-phenyl-15-deoxy-15-fluoro-18,1
9,20-trinor PGD ₁ , 15-deoxy-15-
Fluoro-13,14-dihydroPGD ₁ , 16-
(3,5-dichlorophenoxy) -15-deoxy-1
5-fluoro-13,14-dihydro-17,18,1
9,20-tetranor PGD ₁ , 16- (3,4-dichlorophenoxy) -15-deoxy-15-fluoro-
13,14-dihydro-17,18,19,20-tetranor PGD ₁ .

16- (3-chlorophenoxy) -15-
Deoxy-15-fluoro-13,14-dihydro-1
7,18,19,20- tetranor PGD _1, 16-
(3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-13,14-dihydro-17,1
8,19,20-tetranor PGD ₁ , 16-phenoxy-15-deoxy-15-fluoro-13,14-dihydro-17,18,19,20-tetranor PGD
_1, 17-phenyl-15-deoxy-15-fluoro-13,14-dihydro-18,19,20-trinor PGD _1, 15-deoxy-15-fluoro-3-oxa-17,18,19,20 Tetranor PGD ₁ , 1
6- (3,5-dichlorophenoxy) -15-deoxy-15-fluoro-3-oxa-17,18,19,2
0-tetranor PGD ₁ , 16- (3,4-dichlorophenoxy) -15-deoxy-15-fluoro-3-oxa-17,18,19,20-tetranor PGD ₁ .

16- (3-chlorophenoxy) -15-
Deoxy-15-fluoro-3-oxa-17,18,
19,20-tetranor PGD ₁ , 16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-13,14-dihydro-3-oxa-17,1
8,19,20-tetranor PGD ₁ , 16-phenoxy-15-deoxy-15-fluoro-13,14-dihydro-3-oxa-17,18,19,20-tetranor PGD ₁ , 17-phenyl-15- Deoxy-15
-Fluoro-13,14-dihydro-3-oxa-1
8,19,20-trinor PGD ₁ , N-methanesulfonyl-15-deoxy-15-fluoro-17,18,
19,20-tetranor PGD ₁ carboxamide, N-
Methanesulfonyl-16- (3,5-dichlorophenoxy) -15-deoxy-15-fluoro-17,18,
19,20-tetranor PGD ₁ carboxamide, N-
Methanesulfonyl-16- (3,4-dichlorophenoxy) -15-deoxy-15-fluoro-17,18,
19,20-tetranor PGD ₁ carboxamide.

N-methanesulfonyl-16- (3-chlorophenoxy) -15-deoxy-15-fluoro-1
7,18,19,20- tetranor PGD _{1-carboxamide,} N- methanesulfonyl-16- (3-trifluoromethylphenoxy) -15-deoxy-15-fluoro-tetranor-PGD _{1-carboxamide,} N-methanesulfonyl-16-phenoxy-15-deoxy-15-fluoro-17,18,1
9,20-tetranor PGD ₁ carboxamide, N-methanesulfonyl-17-phenyl-15-deoxy-1
5-Fluoro-18,19,20-trinor PGD ₁ carboxamide.

9,15-dideoxy-15-fluoro-
PGD ₁ methyl ester, 9,15-dideoxy-15
-Fluoro-PGD ₁ ethyl ester, 9,15-dideoxy-15-fluoro-PGD ₁ isopropyl ester, 16- (3,5-dichlorophenoxy) -9,15
-Dideoxy-15-fluoro-17,18,19,2
0-tetranor PGD ₁ methyl ester, 16- (3,
5-dichlorophenoxy) -9,15-dideoxy-1
5-fluoro-17,18,19,20-tetranor P
GD ₁ ethyl ester, 16- (3,5-dichlorophenoxy) -9,15-dideoxy-15-fluoro-1
7,18,19,20-tetranor PGD ₁ isopropyl ester.

16- (3,4-dichlorophenoxy)-
9,15-dideoxy-15-fluoro-17,18,
19,20-tetranor PGD ₁ methyl ester, 16
-(3,4-dichlorophenoxy) -9,15-dideoxy-15-fluoro-17,18,19,20-tetranor PGD ₁ ethyl ester, 16- (3,4-dichlorophenoxy) -9,15-dideoxy -15-fluoro-17,18,19,20-tetranor PGD ₁ isopropyl ester, 16- (3-chlorophenoxy)
-9,15-Dideoxy-15-fluoro-17,1
8,19,20-tetranor PGD ₁ methyl ester,
16- (3-chlorophenoxy) -9,15-dideoxy-15-fluoro-17,18,19,20-tetranor PGD ₁ ethyl ester, 16- (3-chlorophenoxy) -9,15-dideoxy-15 Fluoro-1
7,18,19,20-tetranor PGD ₁ isopropyl ester.

16- (3-trifluoromethylphenoxy) -9,15-dideoxy-15-fluoro-17,
18,19,20-tetranor PGD ₁ methyl ester, 16- (3-trifluoromethylphenoxy)-
9,15-dideoxy-15-fluoro-17,18,
19,20-tetranor PGD ₁ ethyl ester, 16
-(3-trifluoromethylphenoxy) -9,15-
Dideoxy-15-fluoro-17,18,19,20
-Tetranor PGD ₁ isopropyl ester, 16-phenoxy-9,15-dideoxy-15-fluoro-1
7,18,19,20-tetranor PGD ₁ methyl ester, 16-phenoxy-9,15-dideoxy-15
-Fluoro-17,18,19,20-tetranor PG
D ₁ ethyl ester, 16-phenoxy-9,15-dideoxy-15-fluoro-17,18,19,20-
Tetranor PGD ₁ isopropyl ester.

17-phenyl-9,15-dideoxy-
15-Fluoro-18,19,20-trinor PGD ₁
Methyl ester, 17-phenyl-9,15-dideoxy-15-fluoro-18,19,20-trinor PG
D ₁ ethyl ester, 17-phenyl-9,15-dideoxy-15-fluoro-18,19,20-trinor PGD ₁ isopropyl ester, 9,15-dideoxy-15-fluoro-13,14-dihydro PGD ₁ methyl ester , 9,15-Dideoxy-15-fluoro-
13,14-dihydroPGD ₁ ethyl ester, 9.1
5-Dideoxy-15-fluoro-13,14-dihydroPGD ₁ isopropyl ester.

16- (3,5-dichlorophenoxy)-
9,15-dideoxy-15-fluoro-13,14-
Dihydro-17,18,19,20-tetranor PGD
₁ methyl ester, 16- (3,5-dichlorophenoxy) -9,15-dideoxy-15-fluoro-13,
14-dihydro-17,18,19,20-tetranor PGD ₁ ethyl ester, 16- (3,5-dichlorophenoxy) -9,15-dideoxy-15-fluoro-
13,14-dihydro-17,18,19,20-tetranor PGD ₁ isopropyl ester.

16- (3,4-dichlorophenoxy)-
9,15-dideoxy-15-fluoro-13,14-
Dihydro-17,18,19,20-tetranor PGD
₁ methyl ester, 16- (3,4-dichlorophenoxy) -9,15-dideoxy-15-fluoro-13,
14-dihydro-17,18,19,20-tetranor PGD ₁ ethyl ester, 16- (3,4-dichlorophenoxy) -9,15-dideoxy-15-fluoro-
13,14-dihydro-17,18,19,20-tetranor PGD ₁ isopropyl ester, 16- (3-chlorophenoxy) -9,15-dideoxy-15-fluoro-13,14-dihydro-17,18,19 , 20
-Tetranor PGD ₁ methyl ester, 16- (3-chlorophenoxy) -9,15-dideoxy-15-fluoro-13,14-dihydro-17,18,19,20
-Tetranor PGD ₁ ethyl ester, 16- (3-chlorophenoxy) -9,15-dideoxy-15-fluoro-13,14-dihydro-17,18,19,20
-Tetranor PGD ₁ isopropyl ester, 16-
(3-trifluoromethylphenoxy) -9,15-dideoxy-15-fluoro-13,14-dihydro-1
7,18,19,20-tetranor PGD ₁ methyl ester, 16- (3-trifluoromethylphenoxy)-
9,15-dideoxy-15-fluoro-13,14-
Dihydro-17,18,19,20-tetranor PGD
₁ ethyl ester, 16- (3-trifluoromethylphenoxy) -9,15-dideoxy-15-fluoro-
13,14-dihydro-17,18,19,20-tetranor PGD ₁ isopropyl ester.

16-phenoxy-9,15-dideoxy-15-fluoro-13,14-dihydro-17,1
8,19,20-tetranor PGD ₁ methyl ester,
16-phenoxy-9,15-dideoxy-15-fluoro-13,14-dihydro-17,18,19,20
-Tetranor PGD ₁ ethyl ester, 16-phenoxy-9,15-dideoxy-15-fluoro-13,1
4-dihydro-17,18,19,20-tetranor P
GD ₁ isopropyl ester, 17-phenyl-9,1
5-dideoxy-15-fluoro-13,14-dihydro-18,19,20-trinor PGD ₁ methyl ester, 17-phenyl-9,15-dideoxy-15-fluoro-13,14-dihydro-18,19, 20-trinor PGD ₁ ethyl ester, 17-phenyl-9,
15-Dideoxy-15-fluoro-13,14-dihydro-18,19,20-trinor PGD ₁ isopropyl ester.

9,15-dideoxy-15-fluoro-
3-oxa-17,18,19,20-tetranor PG
D ₁ methyl ester, 9,15-dideoxy-15-fluoro-3-oxa-17,18,19,20-tetranor PGD ₁ ethyl ester, 9,15-dideoxy-15-fluoro-3-oxa-17,18 , 19,2
0-tetranor PGD ₁ isopropyl ester, 16-
(3,5-dichlorophenoxy) -9,15-dideoxy-15-fluoro-3-oxa-17,18,19,
20-tetranor PGD ₁ methyl ester, 16-
(3,5-dichlorophenoxy) -9,15-dideoxy-15-fluoro-3-oxa-17,18,19,
20-tetranor PGD ₁ ethyl ester, 16-
(3,5-dichlorophenoxy) -9,15-dideoxy-15-fluoro-3-oxa-17,18,19,
20-tetranor PGD ₁ isopropyl ester, 16
-(3,4-Dichlorophenoxy) -9,15-dideoxy-15-fluoro-3-oxa-17,18,1
9,20-tetranor PGD ₁ methyl ester, 16-
(3,4-dichlorophenoxy) -9,15-dideoxy-15-fluoro-3-oxa-17,18,19,
20-tetranor PGD ₁ ethyl ester, 16-
(3,4-dichlorophenoxy) -9,15-dideoxy-15-fluoro-3-oxa-17,18,19,
20-tetranor PGD ₁ isopropyl ester.

16- (3-chlorophenoxy) -9,1
5-dideoxy-15-fluoro-3-oxa-17,
18,19,20-tetranor PGD ₁ methyl ester, 16- (3-chlorophenoxy) -9,15-dideoxy-15-fluoro-3-oxa-17,18,1
9,20-tetranor PGD ₁ ethyl ester, 16-
(3-chlorophenoxy) -9,15-dideoxy-1
5-fluoro-3-oxa-17,18,19,20-
Tetranor PGD ₁ isopropyl ester, 16- (3
-Trifluoromethylphenoxy) -9,15-dideoxy-15-fluoro-3-oxa-17,18,1
9,20-tetranor PGD ₁ methyl ester, 16-
(3-trifluoromethylphenoxy) -9,15-dideoxy-15-fluoro-3-oxa-17,18,
19,20-tetranor PGD ₁ ethyl ester, 16
-(3-trifluoromethylphenoxy) -9,15-
Dideoxy-15-fluoro-3-oxa-17,1
8,19,20-tetranor PGD ₁ isopropyl ester.

16-phenoxy-9,15-dideoxy-15-fluoro-3-oxa-17,18,19,2
0-tetranor PGD ₁ methyl ester, 16-phenoxy-9,15-dideoxy-15-fluoro-3-oxa-17,18,19,20-tetranor PGD ₁ ethyl ester, 16-phenoxy-9,15-dideoxy- 15-fluoro-3-oxa-17,18,19,
20-tetranor PGD ₁ isopropyl ester, 17
-Phenyl-9,15-dideoxy-15-fluoro-
3-oxa-18,19,20-trinor PGD ₁ methyl ester, 17-phenyl-9,15-dideoxy-
15-Fluoro-3-oxa-18,19,20-trinor PGD ₁ ethyl ester, 17-phenyl-9,1
5-dideoxy-15-fluoro-3-oxa-18,
19,20-trinor PGD ₁ isopropyl ester.

9,15-dideoxy-15-fluoro-
17,18,19,20- tetranor PGD _1, 16-
(3,5-dichlorophenoxy) -9,15-dideoxy-15-fluoro-17,18,19,20-tetranor PGD ₁ , 16- (3,4-dichlorophenoxy)
-9,15-Dideoxy-15-fluoro-17,1
8,19,20-tetranor PGD ₁ , 16- (3-chlorophenoxy) -9,15-dideoxy-15-fluoro-17,18,19,20-tetranor PGD ₁ ,
16- (3-trifluoromethylphenoxy) -9,1
5-dideoxy-15-fluoro-17,18,19,
20-tetranor PGD ₁ , 16-phenoxy-9,1
5-dideoxy-15-fluoro-17,18,19,
20-tetranor PGD ₁ , 17-phenyl-9,15
-Dideoxy-15-fluoro-18,19,20-trinor PGD ₁ , 9,15-dideoxy-15-fluoro-13,14-dihydro PGD ₁ , 16- (3,5-
Dichlorophenoxy) -9,15-dideoxy-15-
Fluoro-13,14-dihydro-17,18,19,
20-tetranor PGD ₁ , 16- (3,4-dichlorophenoxy) -9,15-dideoxy-15-fluoro-13,14-dihydro-17,18,19,20-tetranor PGD ₁ .

16- (3-chlorophenoxy) -9,1
5-dideoxy-15-fluoro-13,14-dihydro-17,18,19,20-tetranor PGD ₁ , 1
6- (3-trifluoromethylphenoxy) -9,15
-Dideoxy-15-fluoro-13,14-dihydro-17,18,19,20-tetranor PGD ₁ , 16
- phenoxy -9,15- dideoxy-15-fluoro-13,14-dihydro-tetranor-PGD _1, 17-phenyl -9,15- dideoxy-15-fluoro-13,14-dihydro −18,
19,20-trinor PGD ₁ , 9,15-dideoxy-15-fluoro-3-oxa-17,18,19,2
0 tetranor PGD _1, 16- (3,5- dichlorophenoxy) -9,15- dideoxy-15-fluoro -
3-oxa-17,18,19,20-tetranor PG
D _1, 16- (3,4- dichlorophenoxy) 9,1
5-dideoxy-15-fluoro-3-oxa-17,
18,19,20-tetranor PGD ₁ .

16- (3-chlorophenoxy) -9,1
5-dideoxy-15-fluoro-3-oxa-17,
18, 19, 20-tetranor PGD ₁ , 16- (3-
(Trifluoromethylphenoxy) -9,15-dideoxy-15-fluoro-13,14-dihydro-3-oxa-17,18,19,20-tetranor PGD ₁ , 1
6-phenoxy-9,15-dideoxy-15-fluoro-13,14-dihydro-3-oxa-17,18,
19,20-tetranor PGD ₁ , 17-phenyl-
9,15-dideoxy-15-fluoro-13,14-
Dihydro-3-oxa-18,19,20-trinor P
GD ₁ .

[0229] N- methanesulfonyl -9,15- dideoxy-15-fluoro-tetranor-PGD _{1-carboxamide,} N- methanesulfonyl-16- (3,5-dichlorophenoxy) -9,15 −
Dideoxy-15-fluoro-17,18,19,20
-Tetranor PGD ₁ carboxamide, N-methanesulfonyl-16- (3,4-dichlorophenoxy) -9,
15-dideoxy-15-fluoro-17,18,1
9,20-tetranor PGD ₁ carboxamide, N-methanesulfonyl-16- (3-chlorophenoxy)-
9,15-dideoxy-15-fluoro-17,18,
19,20-tetranor PGD ₁ carboxamide, N-
Methanesulfonyl-16- (3-trifluoromethylphenoxy) -9,15-dideoxy-15-fluoro-
17,18,19,20- tetranor PGD _{1-carboxamide,} N- methanesulfonyl-16-phenoxy -
9,15-dideoxy-15-fluoro-17,18,
19,20-tetranor PGD ₁ carboxamide, N-
Methanesulfonyl-17-phenyl-9,15-dideoxy-15-fluoro-18,19,20-trinor P
GD ₁ carboxamide.

The fluorine-containing P represented by the general formula (1)
Since the G derivative has an asymmetric carbon in its structure, there are various stereoisomers and optical isomers, and the fluorine-containing PG derivative of the present invention includes all of these stereoisomers, optical isomers and mixtures thereof. Is included.

The 15-deoxy-15-monofluoroPG derivative of the present invention is useful as a medicament, and is useful for treating inflammatory diseases, allergic / immune diseases, digestive system diseases, central nervous system diseases, circulatory system diseases and the like. It can exhibit excellent effects as a therapeutic or as a drug substance. For example, inflammatory diseases include acute hepatitis, chronic hepatitis, cirrhosis, cholecystitis, cholangitis, acute pancreatitis, chronic pancreatitis, chronic peritonitis, acute peritonitis, cystitis, acute nephritis, chronic nephritis, encephalitis, pleurisy, phlebitis, Pericarditis, rhinitis, pharyngitis, otitis media, otitis externa, conjunctivitis, uveitis, retinitis and the like. Allergy
Examples of the immunological disease include bronchial asthma, allergic dermatitis, allergic rhinitis, atopy, rheumatism, collagen disease and the like. Gastrointestinal diseases include gastric ulcer, gastritis, duodenal ulcer, ulcerative colitis, Crohn's disease and the like. Examples of cardiovascular diseases include peripheral circulatory disorders, Berger's disease, Raynaud's disease, angina, myocardial infarction, heart failure, pulmonary hypertension, pulmonary embolism, diabetes, cerebral infarction, cerebral thrombosis, retinopathy, hearing loss, Meniere's disease, etc. No.

[0232]

The present invention will be described in more detail with reference to specific examples below, but the present invention is not limited to these examples.

[Example 1] (1S, 5R, 6R, 7R) -2
-Oxa-7-benzoyloxy-6-[(1E) -4
Synthesis Example of -Phenoxy-3-oxo-1-butenyl] -bicyclo [3.3.0] octan-3-one A solution of 86.0 g of dimethyl 2-oxo-3-phenoxypropylphosphonate in THF (1500 ml) was iced. Under cooling, 12.5 g of lithium chloride and 29.0 g of triethylamine were added. After stirring for 15 minutes, (1S, 5R, 6R, 7
R) -6-Formyl-7-benzoyloxy-2-oxa-bicyclo [3.3.0] octan-3-one
1 g of a THF (300 ml) solution was added. After stirring at 0 ° C. for 1 hour, the reaction solution was poured into a saturated ammonium chloride aqueous solution / ethyl acetate 1/1 mixture and separated. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were dried and concentrated. Silica gel column chromatography (hexane / ethyl acetate
1 / 3-2 / 1) to give 50.0 g of the title compound.

¹ H NMR (CDCl ₃ ) δ (ppm): 2.29 (ddd, J = 15.6,
4.9,0.2Hz, 1H), 2.45-2.51 (m, 1H), 2.60 (dt, J = 15.6,6.6H
z, 1H), 2.83-2.95 (m, 3H), 4.67 (s, 2H), 5.08 (td, J = 4.6,1.7
Hz, 1H), 5.31 (m, 1H), 6.60 (dd, J = 15.6,1.0Hz, 1H), 6.84-6.
87 (m, 2H), 6.91 (dd, J = 15.6,7.8Hz, 1H), 6.98 (t, J = 7.3Hz, 1
H), 7.25-7.29 (m, 2H), 7.44 (t, J = 7.3 Hz, 2H), 7.58 (dt, J = 7.
3,1.2Hz, 1H), 7.97 (dd, J = 8.3,1.2Hz, 2H).

[Example 2] (1S, 5R, 6R, 7R) -2
-Oxa-7-benzoyloxy-6-[(1E) -3
Synthesis Example of -Hydroxy-4-phenoxy-1-butenyl] -bicyclo [3.3.0] octan-3-one A solution of 4.35 g of the enone synthesized in Example 1 in a solution of 150 ml of tetrahydrofuran was dissolved. Cooled to 78 ° C. There, (+)-diisopinocan phenylchloroborane 5.1
5 g was added and the temperature was raised to -20 ° C. After stirring as it was overnight, a saturated aqueous ammonium chloride solution was poured, and the mixture was extracted with ethyl acetate. The combined organic layer was dried and concentrated, and then subjected to silica gel column chromatography (hexane / ethyl acetate 1/1).
1-2 / 3) to give 3.2 g of the title compound.

¹ H NMR (CDCl ₃ ) δ (ppm): 2.26 (ddd, J = 15.1,
3.4,1.5Hz, 1H), 2.53 (m, 1H), 2.62 (dt, J = 15.7,6.4Hz, 1H),
2.77-2.91 (m, 3H), 3.80 (dd, J = 9.3,7.8Hz, 1H), 3.95 (dd, J =
9.3,3.4Hz, 1H), 4.53 (m, 1H), 5.08 (dt, J = 6.4,2.0Hz, 1H),
5.28 (dd, J = 11.7,5.4Hz, 1H), 5.73 (dd, J = 15.6,5.3Hz, 1H),
5.81 (dd, J = 15.6,7.3Hz, 1H), 6.86 (dd, J = 8.8,1.0Hz, 2H),
6.97 (t, J = 7.3Hz, 1H), 7.23-7.30 (m, 2H), 7.41-7.46 (m, 2
H), 7.56 (m, 1H), 7.98-8.00 (m, 2H).

[Example 3] (1S, 5R, 6R, 7R) -2
-Oxa-7-benzoyloxy-6-[(1E) -3
-Hydroxy-4-phenoxy] -bicyclo [3.3.
[0] Synthesis Example of Octan-3-one Allyl alcohol synthesized in Example 2 was dissolved in a solution of 3.0 g of ethanol (100 ml). 5 ml of water and 173.5 mg of sodium nitrite were added thereto, and further 5% Pd-C was added.
(352 mg) was added and the mixture was suspended, and the mixture was stirred under a hydrogen atmosphere at room temperature for 2 hours. The reaction solution was filtered through celite, dried and concentrated. Purify by silica gel column chromatography (hexane / ethyl acetate 1/1) to obtain the title compound.
1 g was obtained.

¹ H NMR (CDCl ₃ ) δ (ppm): 1.49-1.74 (m, 4H),
2.15 (m, 1H), 2.30-2.41 (m, 2H), 2.48 (dd, J = 18.6,2.4Hz, 1
H), 2.74 (m, 1H), 2.89 (dd, J = 18.1,10.7Hz, 1H), 3.84 (dd, J =
9.4,6.8Hz, 1H), 3.92-3.99 (m, 2H), 5.06 (m, 1H), 5.25 (m, 1
H), 6.88 (d, J = 7.8Hz, 2H), 6.95 (t, J = 7.3Hz, 1H), 7.27 (t, J =
7.3Hz, 2H), 7.42 (t, J = 7.8Hz, 2H), 7.54 (t, J = 7.3Hz, 1H), 7.
99 (d, J = 7.3Hz, 2H).

[Example 4] (1S, 5R, 6R, 7R) -2
-Oxa-7-benzoyloxy-6-[(1E) -3
-Fluoro-4-phenoxy] -bicyclo [3.3.
[0] Synthesis Example of Octan-3-one 3.1 g of the alcohol synthesized in Example 3 was treated with methylene chloride (9
0 ml) to the solution was added 3.9 g of morpholinosulfatrifluoride at -78 ° C. The temperature in the system was raised to 0 ° C,
After stirring for an hour, the mixture was poured into saturated aqueous sodium hydrogen carbonate and extracted with ethyl acetate. Silica gel column chromatography (hexane /
Purification with ethyl acetate (2/1) gave 840 mg of the title compound.

¹ H NMR (CDCl ₃ ) δ (ppm): 1.57 (m, 1H), 1.70
(m, 1H), 1.80-2.04 (m, 2H), 2.21 (m, 1H), 2.37 (m, 1H), 2.45
(dt, J = 15.8,5.8Hz, 1H), 2.53 (dd, J = 18.3,2.7Hz, 1H), 2.73
(m, 1H), 2.94 (dd, J = 18.3,10.5Hz, 1H), 4.02-4.13 (m, 2H),
4.86 (m, 1H), 5.11 (dt, J = 5.8,1.5Hz, 1H), 5.28 (dt, J = 5.8,
2.9Hz, 1H), 6.89-6.91 (m, 2H), 6.98 (m, 1H), 7.27-7.31 (m, 2
H), 7.42-7.46 (m, 2H), 7.56 (m, 1H), 7.98-8.00 (m, 2H). ¹⁹ F
_{NMR (CDCl 3) δ (ppm} ): - 188.7 (m).

[Example 5] (1S, 5R, 6R, 7R) -2
Synthesis Example of -Oxa-7-hydroxy-6-[(1E) -3-fluoro-4-phenoxy] -bicyclo [3.3.0] octan-3-one 840 mg of the fluoride synthesized in Example 4 was treated with 8 m of methanol.
and 240 mg of potassium carbonate was added thereto.
Stirred for hours. Water was added to the system, and extracted with ethyl acetate. Purification by silica gel column chromatography (hexane / ethyl acetate 1/1) gave 500 mg of the title compound.

¹ H NMR (CDCl ₃ ) δ (ppm): 1.36 (m, 1H), 1.59
(m, 1H), 1.74-1.92 (m, 3H), 2.04 (m, 1H), 2.25 (dt, J = 19.
8,5.6Hz, 1H), 2.51 (dd, J = 18.8,2.9Hz, 1H), 2.53 (m, 1H), 2.
79 (dd, J = 18.8,11.0Hz, 1H), 4.00-4.13 (m, 2H), 4.80 (m, 1
H), 4.94 (td, J = 6.8,2.2Hz, 1H), 6.89-6.92 (m, 2H), 6.97 (m,
1H), 7.26-7.30 (m, 2H). ¹⁹ F NMR (CDCl ₃ ) δ (ppm): -187.5 (m).

[Example 6] (1S, 5R, 6R, 7R) -2
-Oxa-7-tetrahydropyranyloxy-6-
Synthesis Example of [(1E) -3-fluoro-4-phenoxy] -bicyclo [3.3.0] octan-3-one (1S, 5R, 6R, 7R) -2-oxa-7 synthesized in Example 5. -Hydroxy-6-[(1E) -3-fluoro-
4-phenoxy] -bicyclo [3.3.0] octane-
Dissolve 500 mg of 3-one in 5 ml of methylene chloride and add thereto 205 mg of 3,4-dihydro-2H-pyran at room temperature.
And p-toluenesulfonic acid monohydrate (3.0 mg) were added. After stirring for 20 minutes, 5 drops of pyridine were added, and the mixture was further diluted with diethyl ether (50 ml).
5 x 2). The organic layer was dried and concentrated, and the obtained crude product was purified by silica gel column chromatography (hexane / ethyl acetate 1/1) to give the title compound 5
70 mg were obtained.

¹ H NMR (CDCl ₃ ) δ (ppm): 1.36-2.10 (m, 12
H), 2.10-2.79 (m, 4H), 3.40-3.47 (m, 1H), 3.75-3.84 (m, 1
H), 4.00-4.13 (m, 2H), 4.64 (dt, J = 16.1,3.2Hz, 1H), 4.80
(m, 1H), 4.89 (m, 1H), 6.87-6.92 (m, 2H), 6.97 (m, 1H), 7.29
-7.33 (m, 2H). ¹⁹ F NMR (CDCl ₃ ) δ (ppm): -187.3 (m).

[Example 7] (1S, 5R, 6R, 7R) -2
Synthesis Example of -oxa-3-hydroxy-7-tetrahydropyranyloxy-6-[(1E) -3-fluoro-4-phenoxy] -bicyclo [3.3.0] octane Synthesized in Example 6 (1S, 5R) , 6R, 7R) -2-oxa-7-tetrahydropyranyloxy-6-[(1E)
-3-Fluoro-4-phenoxy] -bicyclo [3.
3.0] Octane-3-one (570 mg) in THF (5 m
l), and a solution of diisobutylaluminum hydride in toluene (1.01 M, 3.6 m
l) and stirred for 30 minutes.
1N hydrochloric acid (20 ml) was added, and the mixture was extracted with ethyl acetate. The organic layer was dried and concentrated, and the resulting crude product was subjected to silica gel column chromatography (hexane / ethyl acetate 3).
/ 2-2 / 3) to give 515 mg of the title compound.

¹ H NMR (CDCl ₃ ) δ (ppm): 1.36-2.62 (m, 15
H), 2.81-3.08 (m, 1H), 3.40-3.89 (m, 2H), 3.94-4.23 (m, 2
H), 4.40-4.73 (m, 2H), 4.80-4.89 (m, 2H), 6.88-6.91 (m, 2
H), 6.95 (m, 1H), 7.26-7.28 (m, 2H). ¹⁹ F NMR (CDCl ₃ ) δ (ppm): -188.6 (m).

[0247] [Example 8] 16-phenoxy-15-deoxy-15-fluoro-11-tetrahydropyranyloxy-tetranor-PGF ₂ Synthesis Example of alpha 4-carboxybutyl triphenyl phosphonium bromide 3 To a suspension of 2.8 g of THF (25 ml) was added a solution of sodium bis (trimethylsilyl) amide in THF (1 M, 8).
ml) and stirred at room temperature for 1 hour. A solution of 515 mg of lactol synthesized in Example 7 in THF (5 ml) was added at 0 ° C., and the mixture was stirred as it was for 3 hours. The reaction was stopped by adding ice water, washed with diethyl ether, the aqueous layer was acidified, extracted with ethyl acetate, dried, and the solvent was distilled off. The obtained carboxylic acid crude product was subjected to silica gel column chromatography (hexane / hexane Purification with ethyl acetate (2/3) gave 500 mg of the title compound.

¹ H NMR (CDCl ₃ ) δ (ppm): δ 1.42-2.72 (m, 21
H), 3.40-3.88 (m, 2H), 4.05-4.23 (m, 4H), 4.40-4.70 (m, 1
H), 4.86 (m, 1H), 5.31-5.48 (m, 2H), 6.89-6.93 (m, 2H), 6.98
(m, 1H), 7.28-7.30 (m, 2H). ¹⁹ F NMR (CDCl ₃ ) δ (ppm): -187.8 (m).

Example 9 Synthesis of 16-phenoxy-15-deoxy-15-fluoro-11-tetrahydropyranyloxy-17,18,19,20-tetranor PGE ₂ 16-phenoxy-15 synthesized in Example 8 -Deoxy-1
5-fluoro-11-tetrahydropyranyloxy-1
7,18,19,20-tetranor PGF ₂ α200m
g was dissolved in methylene chloride (4 ml). Thereto was added celite (400 mg) and 360 mg of pyridinium chlorochromate at room temperature, and the mixture was stirred for 2 hours. The reaction solution was filtered through celite, washed with diethyl ether,
The crude product obtained by evaporating the solvent was purified by silica gel column chromatography (hexane / ethyl acetate 1/1) to obtain 103 mg of the title compound.

¹ H NMR (CDCl ₃ ) δ (ppm): 1.42-2.84 (m, 21
H), 3.45 (m, 1H), 3.79 (m, 1H), 4.03-4.21 (m, 3H), 4.62 (m, 1
H), 4.88 (m, 1H), 5.28-5.43 (m, 2H), 6.85-6.90 (m, 2H), 6.99
(m, 1H), 7.26-7.31 (m, 2H). ¹⁹ F NMR (CDCl ₃ ) δ (ppm): -188.2 (m).

[Example 10] Synthesis example of 16-phenoxy-15-deoxy-15-fluoro-17,18,19,20-tetranor PGE ₂ 16-phenoxy-15-deoxy-1 synthesized in Example 9
5-fluoro-11-tetrahydropyranyloxy-1
7,18,19,20-tetranor PGE ₂ 103mg
Was dissolved in acetone (3 ml). Thereto, p-toluenesulfonic acid monohydrate (4.0 mg) was added, and the mixture was stirred at room temperature for 2 hours. After adding aqueous sodium bicarbonate (5 ml), the mixture was extracted with ethyl acetate, dried and the solvent was distilled off. The obtained crude product was purified by thin-layer chromatography (hexane / ethyl acetate 1/1) to obtain 64 mg of the title compound. .

¹ H NMR (CDCl ₃ ) δ (ppm): 1.43-2.40 (m, 15
H), 3.92-4.18 (m, 3H), 4.86 (m, 1H), 5.32-5.46 (m, 2H), 6.87
-6.92 (m, 2H), 6.99 (m, 1H), 7.28-7.31 (m, 2H). ¹⁹ F NMR (CDCl ₃ ) δ (ppm): -188.1 (m).

[0253] [Example 11] 16-phenoxy-15-deoxy-15-fluoro-11-tetrahydropyranyloxy-tetranor-PGF ₂ alpha
Synthesis example of isopropyl ester 16-phenoxy-15-deoxy-1 synthesized in Example 8
5-fluoro-11-tetrahydropyranyloxy-1
7,18,19,20-tetranor PGF ₂ α300m
g, 570 mg of 1,8-diazabicyclo [5.4.0] undec-7-ene and 690 mg of 2-iodopropane were added to an acetone (3 ml) solution, and the mixture was stirred at 30 ° C. for 10 hours. The reaction solution was diluted with ethyl acetate, washed with a saturated saline solution, a 3% aqueous citric acid solution and an aqueous sodium hydrogen carbonate solution, dried and concentrated, and then purified by silica gel column chromatography (hexane / ethyl acetate 2/3) to give 287 mg of the title compound. Obtained.

¹ H-NMR (CDCl ₃ ) δ (ppm): 1.23 (d, J = 6.01, 6
H), 1.42-2.72 (m, 21H), 3.40-3.88 (m, 2H), 4.05-4.23 (m, 4
H), 4.40-4.70 (m, 1H), 4.86 (m, 1H), 4.99 (m, 1H), 5.31-5.48
(m, 2H), 6.87-6.90 (m, 2H), 6.98 (m, 1H), 7.28-7.32 (m, 2
H). ¹⁹ F-NMR (CDCl ₃ ) δ (ppm): -187.9 (m).

[Example 12] Synthesis example of 16-phenoxy-15-deoxy-15-fluoro-11-tetrahydropyranyloxy-17,18,19,20-tetranor PGE ₂ isopropyl ester 16-phenoxy synthesized in Example 11 -15-deoxy-
15-fluoro-11-tetrahydropyranyloxy-
17,18,19,20- tetranor PGF ₂ alpha isopropyl ester 287mg methylene chloride (4m
l). There, celite (500m
g) and 480 mg of pyridinium chlorochromate were added, and the mixture was stirred as it was for 3 hours. The reaction solution was filtered through celite, washed with diethyl ether, and the solvent was distilled off. The resulting crude product was purified by silica gel column chromatography (hexane / ethyl acetate 4/1) to give the title compound 145.
mg was obtained.

¹ H NMR (CDCl ₃ ) δ (ppm): 1.21 (d, J = 6.11, 6
H), 1.41-2.40 (m, 21H), 3.45 (m, 1H), 3.79 (m, 1H), 4.01-
4.25 (m, 3H), 4.63 (m, 1H), 4.83 (m, 1H), 4.96 (m, 1H),
5.24-5.43 (m, 2H), 6.89-6.92 (m, 2H), 6.99 (m, 1H), 7.28
-7.31 (m, 2H) ¹⁹ F NMR (CDCl ₃ ) δ (ppm): -188.4 (m).

Example 13 Synthesis Example of 16-phenoxy-15-deoxy-15-fluoro-17,18,19,20-tetranor PGE ₂ isopropyl ester 16-phenoxy-15-deoxy-synthesized in Example 12
15-fluoro-11-tetrahydropyranyloxy-
145 mg of 17,18,19,20-tetranor PGE ₂ isopropyl ester was dissolved in acetone (3 ml). There, p-toluenesulfonic acid monohydrate (6.0)
mg) and stirred at room temperature for 3 hours. Aqueous sodium bicarbonate (5 ml)
Was added, followed by extraction with ethyl acetate. After drying, the solvent was distilled off. The obtained crude product was purified by silica gel column chromatography (hexane / ethyl acetate 1/1) to obtain 76 mg of the title compound.

¹ H NMR (CDCl ₃ ) δ (ppm): 1.21 (d, J = 6.11, 6
H), 1.40-2.42 (m, 15H), 3.92-4.18 (m, 3H), 4.86 (m, 1H),
5.0 (m, 1H), 5.32-5.46 (m, 2H), 6.87-6.92 (m, 2H), 6.99
(m, 1H), 7.26-7.30 ( m, 2H) 19 F NMR (CDCl 3) δ (ppm): - 188.1 (m).

[0259]

According to the present invention, 1 useful as a pharmaceutical
15-monofluoroPG having one fluorine atom at the 5-position
Derivatives are provided.

Claims (11)

[Claims] 1. A derivative of 15-deoxy-15-monofluoro-prostaglandin E, 15-deoxy-15-
Derivatives of monofluoro-prostaglandin D, 15-
Deoxy-15-monofluoro-prostaglandin I
A derivative of 15-deoxy-15-monofluoro-prostaglandin A, a derivative of 15-deoxy-15-monofluoro-prostaglandin B, and 1
A 15-deoxy-15-monofluoro-prostaglandin derivative selected from derivatives of 5-deoxy-15-monofluoro-prostaglandin J, or a salt thereof (provided that the 15-position of a prostaglandin having a natural type skeleton) Excluding natural 15-deoxy-15-monofluoroprostaglandins, which are derivatives in which one fluorine atom has been introduced into the above, and salts thereof.) 2. Derivatives of 15-deoxy-15-monofluoro-prostaglandin E and 15-deoxy-1
A 15-deoxy-15-monofluoro-prostaglandin derivative selected from 5-monofluoro-prostaglandin D derivatives, or a salt thereof (provided that a fluorine atom is located at the 15-position of a prostaglandin having a natural skeleton) Natural type 15-deoxy-1 which is one derivative introduced
Excludes 5-monofluoroprostaglandins E and salts thereof, and natural 15-deoxy-15-monofluoro-prostaglandins D and salts thereof. ). 3. A 15-deoxy-15-monofluoro-prostaglandin derivative represented by the following general formula (1):
Or its salt. Embedded image (However, symbols in the general formula (1) have the following meanings: A: ethylene group, vinylene group, ethynylene group, -OCH
_2- or -SCH _2- . R ¹ : an alkyl group having 1 to 8 carbon atoms, substituted 1 carbon atom
An alkyl group having 8 to 8 carbon atoms, an alkenyl group having 3 to 8 carbon atoms, a substituted alkenyl group having 3 to 8 carbon atoms, an alkynyl group having 3 to 8 carbon atoms, a substituted alkynyl group having 3 to 8 carbon atoms,
C3-8 cycloalkyl group, substituted C3
To 8 cycloalkyl groups, aralkyl groups, substituted aralkyl groups, or aryloxyalkyl groups;
A substituted aryloxyalkyl group. P and Q: each independently —CO—, —CH (OR ² )
-, or -CH ₂ -. However, P and Q are simultaneously -C
O— or not simultaneously —CH (OR ² ) (provided that R
² each independently represents a hydrogen atom or an acyl group. Further, one of R ² and Z may form a single bond together. ). _{X: -CH 2 -, - O-} , or -S-. ^{Z: -OR 3, -NHCOR 4,} -NHSO 2 R 5, -
SR ⁶ , or —NR ⁷ R ⁸ . Also, one of Z and R ² may form a single bond together (provided that
R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , and R ⁸ each independently represent a hydrogen atom, an alkyl group, a substituted alkyl group, an alkenyl group, a substituted alkenyl group, an alkynyl group, a substituted alkynyl group, or a cycloalkyl group. , A substituted cycloalkyl group, an aryl group, a substituted aryl group, an aralkyl group, and a substituted aralkyl group. ). Overlap between solid and dashed line: single bond, cis double bond, or trans double bond. However, A is an ethylene group, P is -CO-, Q is -CH
(OH) -, X is -CH ₂ -, Z is OH, R ¹ is n- pentyl group, and, when the dotted line and dashed overlapping parts are cis double bonds, and, A is an ethylene group, P is - CH (OH)
-, Q is -CO-, X is -CH ₂ -, Z is OH, R ¹ is n- pentyl group and, when the dotted line and dashed overlapping parts are cis double bonds, excluding. ) 4. The method according to claim 3, wherein A is an ethylene group or a vinylene group.
Prostaglandin derivatives or salts thereof. 5. The method according to claim 3, wherein X is —CH ₂ —.
A 15-deoxy-15-monofluoro-prostaglandin derivative according to the above, or a salt thereof. 6. The 15-deoxy-15-monofluoro-prostaglandin derivative according to claim 3, wherein R ² is a hydrogen atom, or a salt thereof. 7. The 15-deoxy-15-monofluoro-prostaglandin derivative or a salt thereof according to claim ³ , wherein Z is —OR ³ . 8. P is --CO--, and Q is --CH--
And (OR ² ) — or —CH ₂ —.
The 15-deoxy-15-monofluoro-prostaglandin derivative according to 5, 6, or 7, or a salt thereof. 9. P is —CH (OR ² ) — or —CH ₂ —
And Q is -CO-.
The 15-deoxy-15-monofluoro-prostaglandin derivative according to 6 or 7, or a salt thereof. 10. The method according to claim 3, wherein R ¹ is an aryloxyalkyl group which may have a substituent.
A 15-deoxy-15-monofluoro-prostaglandin derivative according to 7, 8, or 9, or a salt thereof. 11. R ¹ is a phenoxymethyl group, 3,5-
A dichlorophenoxymethyl group or a 3-chlorophenoxymethyl group.
Or the 15-deoxy-15-monofluoro-prostaglandin derivative according to 10, or a salt thereof.