Certain 5,6-dihydro-prostacyclin analogs

Processes for preparing 5,6-dihydro-prostacyclin analogs, which are 9-deoxy-6,9-cyclic ethers of prostaglandin F.sub.1.alpha. -type compounds, illustrated for example, by a compound of the formula ##STR1## wherein .about. indicates alpha or beta configuration; including the products and intermediates produced therein, said products having pharmacological utility. There are also provided mercury derivatives of these 5,6-dihydro-prostacyclins, illustrated, for example, by a compound of the formula ##STR2## wherein G is nitrato, iodo, chloro, bromo, acetato, trifluoroacetato, or benzoato, and wherein .about. indicates alpha or beta configuration, said products having pharmacological activity, and useful as intermediates in preparing the above compounds.

I claim:

1. A cyclic ether of the formula ##STR185## wherein D is (1) a valence bond; (2) --(CH.sub.2).sub.d -- where d is 1, 2, 3, 4, or 5; (3) --CH.dbd.CH--A-- where A is a valence bond or --(CH.sub.2).sub.h -- where h is 1, 2, or 3; or (4) --CH.sub.2 --O--CH.sub.2 --Y-- where Y is a valence bond or --(CH.sub.2).sub.k -- where k is 1 or 2; wherein R.sub.2 is ##STR186## wherein C.sub.g H.sub.2.sbsb.g is alkylene of 1 to 9 carbon atoms, inclusive, with 1 to 5 carbon atoms, inclusive, in the chain between --CR.sub.5 R.sub.6 -- and terminal methyl, wherein R.sub.5 and R.sub.6 are hydrogen, alkyl of one to 4 carbon atoms, inclusive, or fluoro, being the same or different, with the proviso that one of R.sub.5 and R.sub.6 is fluoro only when the other is hydrogen or fluoro; or ##STR187## wherein R.sub.5 and R.sub.6 are as defined above with the proviso that neither R.sub.5 nor R.sub.6 is fluoro when Z is oxa (--O--); wherein Z represents an oxa atom (--O--) or C.sub.j H.sub.2.sbsb.j wherein C.sub.j H.sub.2.sbsb.j is a valence bond or alkylene of one to 9 carbon atoms, inclusive, with one to 6 carbon atoms, inclusive between --CR.sub.5 R.sub.6 -- and the phenyl ring; wherein T is alkyl of one to 4 carbon atoms, inclusive, fluoro, chloro, trifluoromethyl, or --OR.sub.7 wherein R.sub.7 is alkyl of 1 to 4 carbon atoms, inclusive, and s is 0, 1, 2 or 3, with the proviso that not more than two T's are other than alkyl and when s is 2 or 3 the T's are either the same or different;

wherein Q.sub.3 is ##STR188## wherein R.sub.3 is hydrogen or alkyl of one to 4 carbon atoms, inclusive; wherein R.sub.23 is ##STR189## wherein R.sub.31 is (1) --COOR.sub.32

(2) --ch.sub.2 n(r.sub.18).sub.2 ##STR190## wherein R.sub.32 is wherein R.sub.32 is

(a) cycloalkyl of 3 to 10 carbon atoms, inclusive,

(b) aralkyl of 7 to 12 carbon atoms, inclusive

(c) phenyl,

(d) phenyl substituted with 1, 2, or 3 chloro or alkyl of one to 4 carbon atoms, inclusive, ##STR191## wherein R.sub.34 is phenyl, p-bromophenyl, p-biphenylyl, p-nitrophenyl, p-benzamido phenyl, or 2-naphthyl, wherein R.sub.35 is hydrogen or benzoyl, and

wherein R.sub.18 is hydrogen, alkyl of one to 12 carbon atoms, inclusive, benzyl, or phenyl, being the same or different; wherein .about. indicates attachment in alpha or beta configuration; including the lower alkanoates thereof.

2. A compound according to claim 1 wherein Q.sub.3 is ##STR192## wherein R.sub.3 is as defined in claim 1.

3. A compound according to claim 2 wherein R.sub.3 is hydrogen and R.sub.23 is ##STR193##

4. A compound according to claim 3 wherein D is a valence bond or --(CH.sub.2).sub.3 -- wherein d is 1, 2, 3, 4, or 5.

5. A compound according to claim 4 wherein D is trimethylene.

6. A compound according to claim 5 wherein R.sub.2 is n-pentyl.

7. A compound according to claim 6 wherein R.sub.31 is ##STR194## wherein R.sub.18 is hydrogen, alkyl of 1 to 12 carbon atoms, inclusive, benzyl, or phenyl, being the same or different.

8. A compound according to claim 7 wherein one R.sub.18 is hydrogen, methyl, or phenyl and the other R.sub.18 is hydrogen.

9. 9-Deoxy-6.xi.,9.alpha.-epoxy-PGF.sub.1, amide, less polar and more polar isomers, compounds according to claim 8.

10. (6S)-PGI.sub.1, amide, a compound according to claim 9.

11. (6R)-PGI.sub.1, amide, a compound according to claim 9.

12. 9-Deoxy-6.xi.,9.alpha.-epoxy-PGF.sub.1, methylamide, less polar and more polar isomers, compounds according to claim 8.

13. (6S)-PGI.sub.1, methylamide, a compound according to claim 12.

14. (6R)-PGI.sub.1, methylamide, a compound according to claim 12.

15. 9-Deoxy-6.xi.,9.alpha.-epoxy-PGF.sub.1, anilide, less polar and more polar isomers, compounds according to claim 8.

16. (6S)-PGI.sub.1, anilide, a compound according to claim 15.

17. (6R)-PGI.sub.1, anilide, a compound according to claim 15.

18. 9-Deoxy-6.xi.,9.alpha.-epoxy-PGF.sub.1, n-butylamide, less polar and more polar isomers, compounds according to claim 7.

19. 9-Deoxy-6.xi.,9.alpha.-epoxy-PGF.sub.1, benzylamide, less polar and more polar isomers, compounds according to claim 7.

20. A compound according to claim 6 wherein R.sub.31 is --COOR.sub.32 wherein R.sub.32 is ##STR195## (g) p-phenylphenacyl.

21. A compound according to claim 5 wherein R.sub.2 is ##STR196##

22. A compound according to claim 2 wherein Q.sub.3 is ##STR197##

23. A compound according to claim 22 wherein R.sub.31 is ##STR198## wherein R.sub.18 is hydrogen, alkyl of 1 to 12 carbon atoms, inclusive, benzyl, or phenyl, being the same or different.

24. A compound according to claim 23 wherein one R.sub.18 is hydrogen, methyl, or phenyl and the other R.sub.18 is hydrogen.

25. 9-Deoxy-6.xi.,9.alpha.-epoxy-15(S)-15-methyl-PGF.sub.1, amide, less polar and more polar isomers, compounds according to claim 24.

26. (6S,15S)-15-Methyl-PGI.sub.1, amide, a compound according to claim 25.

27. (6R,15S)-15-Methyl-PGI.sub.1, amide, a compound according to claim 25.

28. A cyclic ether of the formula ##STR199## wherein D is (1) a valence bond; (2) --(CH.sub.2).sub.d --where d is 1, 2, 3, 4, or 5; (3) --CH.dbd.CH--A-- where A is a valence bond, or --(CH.sub.2).sub.h -- where h is 1, 2, or 3; or (4) --CH.sub.2 --O--CH.sub.2 --Y-- where Y is a valence bond or --(CH.sub.2).sub.k -- where k is 1 or 2;

wherein Q.sub.3 is ##STR200## wherein R.sub.3 is hydrogen or alkyl of 1 to 4 carbon atoms, inclusive; wherein R.sub.23 is ##STR201## wherein R.sub.30 is (1) --COOR.sub.19

(2) --ch.sub.2 n(r.sub.18).sub.2 ##STR202## wherein R.sub.19 is (a) alkyl of 1 to 12 carbon atoms, inclusive,

(b) cycloalkyl of 3 to 10 carbon atoms, inclusive,

(c) aralkyl of 7 to 12 carbon atoms, inclusive,

(d) phenyl,

(e) phenyl substituted with 1, 2, or 3 chloro or alkyl of 1 to 4 carbon atoms, inclusive, ##STR203## wherein R.sub.34 is phenyl, p-bromophenyl, p-biphenylyl, p-nitrophenyl, p-benzamidophenyl, or 2-naphthyl, and wherein R.sub.35 is hydrogen or benzoyl,

(m) hydrogen; or

(n) a pharmacologically acceptable cation; and wherein R.sub.18 is hydrogen, alkyl of 1 to 12 carbon atoms, inclusive, benzyl, or phenyl, being the same or different; and wherein .about. indicates attachment in alpha or beta configuration; including the lower alkanoates thereof.

29. A compound according to claim 28 wherein Q.sub.3 is ##STR204## wherein R.sub.3 is as defined in claim 29.

30. A compound according to claim 29 wherein R.sub.23 is ##STR205##

31. A compound according to claim 30 wherein D is a valence bond or --(CH.sub.2).sub.d --wherein d is 1, 2, 3, 4, or 5.

32. A compound according to claim 31, where, if R.sub.30 is --CH.sub.2 N(R.sub.18).sub.2 or ##STR206## one R.sub.18 is hydrogen, methyl, or phenyl, and the other R.sub.18 is hydrogen, or, if R.sub.30 is --COOR.sub.19, R.sub.19 is (a) hydrogen, (b) methyl, (c) ethyl, ##STR207## (j) p-phenylphenacyl, or (k) a pharmacologically acceptable cation.

33. A cyclic ether of the formula ##STR208## wherein D' is --CH.sub.2 --CH.dbd.CH--A-- or

--(CH.sub.2).sub.T --CF.sub.2 --

wherein A is a valence bond or --(CH.sub.2).sub.h -- where h is 1, 2, or 3; and wherein t is 2, 3, or 4;

wherein Q.sub.3 is ##STR209## wherein R.sub.3 is hydrogen or alkyl of 1 to 4 carbon atoms, inclusive, wherein R.sub.23 is ##STR210## wherein R.sub.25 is ##STR211## wherein C.sub.g H.sub.2.sbsb.g is alkylene of 1 to 9 carbon atoms, inclusive, with 1 to 5 carbon atoms, inclusive, in the chain between -CR.sub.5 R.sub.6 - and terminal methyl, wherein R.sub.5 and R.sub.6 are hydrogen, alkyl of 1 to 4 carbon atoms, inclusive, or fluoro, being the same or different, with the proviso that one of R.sub.5 and R.sub.6 is fluoro only when the other is hydrogen or fluoro; ##STR212## wherein R.sub.5 and R.sub.6 are as defined above with the proviso that neither R.sub.5 nor R.sub.6 is fluoro when Z is oxa (--O--); wherein Z represents an oxa atom (--O--) or C.sub.j H.sub.2.sbsb.j wherein C.sub.j H.sub.2.sbsb.j is a valence bond or alkylene of 1 to 9 carbon atoms, inclusive, with 1 to 6 carbon atoms, inclusive between --CR.sub.5 R.sub.6 -- and the phenyl ring; wherein T is alkyl of one to 4 carbon atoms, inclusive, fluoro, chloro, trifluoromethyl, or --OR.sub.7 -- wherein R.sub.7 is alkyl of one to 4 carbon atoms, inclusive, and s is 0, 1, 2, or 3, with the proviso that not more than two T's are other than alkyl and when s is 2 or 3 and T's are either the same or different; or ##STR213## wherein R.sub.30 is (1) --COOR.sub.19

(2 ) --ch.sub.2 n(r.sub.18).sub.2 ##STR214## wherein R.sub.19 is (a) alkyl of one to 12 carbon atoms, inclusive,

(b) cycloalkyl of 3 to 10 carbon atoms, inclusive,

(c) aralkyl of 7 to 12 carbon atoms, inclusive,

(d) phenyl,

(e) phenyl substituted with 1, 2, or 3 chloro or alkyl of 1 to 4 carbon atoms, inclusive, ##STR215## wherein R.sub.34 is phenyl, p-bromophenyl, p-biphenylyl, p-nitrophenyl, p-benzamidophenyl, or 2-naphthyl, and wherein R.sub.35 is hydrogen or benzoyl,

(m) hydrogen; or

(n) a pharmacologically acceptable cation; and wherein R.sub.18 is hydrogen, alkyl of one to 12 carbon atoms, inclusive, benzyl, or phenyl, being the same or different; and wherein .about. indicates attachment in alpha or beta configuration; including the lower alkanoates thereof.

34. A compound according to claim 33 wherein Q.sub.3 is ##STR216## wherein R.sub.3 is as defined in claim 35.

35. A compound according to claim 34 wherein R.sub.23 is ##STR217##

36. A compound according to claim 35 wherein D' is --(CH.sub.2).sub.t --CF.sub.2 where t is 2, 3, or 4.

37. A compound according to claim 36 wherein t is 2, and where, if R.sub.30 is --CH.sub.2 N(R.sub.18).sub.2 or ##STR218## one R.sub.18 is hydrogen, methyl, or phenyl, and the other R.sub.18 is hydrogen, or, if R.sub.30 is --COOR.sub.19, R.sub.19 is (a) hydrogen, (b) methyl, (c) ethyl, ##STR219## (j) p-phenylphenacyl, or (k) a pharmacologically acceptable cation.

38. A compound according to claim 37 wherein R.sub.25 is n-pentyl.

39. A compound according to claim 37 wherein R.sub.25 is ##STR220##

40. A compound according to claim 37 wherein R.sub.25 is ##STR221##

41. A compound according to claim 37 wherein R.sub.25 is ##STR222##

42. A compound according to claim 35 wherein D' is --CH.sub.2 --CH.dbd.CH--A-- wherein A is a valence bond or --(CH.sub.2).sub.h wherein h is 1, 2, or 3.

43. A compound according to claim 42 wherein A is a valance bond, and where, if R.sub.30 is --CH.sub.2 N(R.sub.18) or ##STR223## one R.sub.18 is hydrogen, methyl, or phenyl, and the other R.sub.18 is hydrogen, or, if R.sub.30 is --COOR.sub.19, R.sub.19 is (a) hydrogen, (b) methyl, (c) ethyl, ##STR224## (j) p-phenylphenacyl, or (k) a pharmacologically acceptable cation.

44. A compound according to claim 43 wherein R.sub.25 is n-pentyl.

45. 9-Deoxy-6.xi., 9.alpha.-epoxy-2,3-trans-didehydro-PGF.sub.1, methyl ester, less polar and more polar isomers, compounds according to claim 44.

46. (2E,6S)-.DELTA..sup.2 -PGI.sub.1, methyl ester, a compound according to claim 45.

47. (2E,6R)-.DELTA.-PGI.sub.1, methyl ester, a compound according to claim 45.

48. A compound according to claim 46 wherein R.sub.25 is ##STR225##

49. 9-Deoxy-6.xi.,9.alpha.-epoxy-2,3-trans-didehydro-16,16-dimethyl-PGF.sub . 1, methyl ester, less polar and more polar isomers, compounds according to claim 48.

50. (2E, 6S)-16,16-Dimethyl-.DELTA..sup.2 -PGI, methyl ester, a compound according to claim 49.

51. (2E,6R)-16,16-Dimethyl-.DELTA..sup.2 -PGI.sub.1, methyl ester, a compound according to claim 49.

52. 9-Deoxy-6.xi.,9.alpha.-epoxy -2,3-trans-didehydro-16,16-dimethyl-PGF.sub.1, less polar and more polar isomers, compounds according to claim 48.

53. (2E,6s)-16,16-dimethyl-.DELTA..sup.2 -PGI.sub.1, a compound according to claim 52.

54. (2E,6R)-16,16-dimethyl-.DELTA..sup.2 -PGI.sub.1, a compound according to claim 52.

55. A compound according to claim 43 wherein R.sub.25 is ##STR226##

56. A comound according to claim 43 wherein R.sub.25 is ##STR227##

57. A cyclic ether of the formula ##STR228## wherein L is (1) a valence bond, (2) --(CH.sub.2).sub.d -- wherein d is 1 to 5 inclusive, (3) --(CH.sub.2).sub.t --CF.sub.2 -- wherein t is 2, 3, or 4, (4) --CH.sub.2 --CH.dbd.CH--A-- wherein A is a valence bond or --(CH.sub.2).sub.h -- wherein h is 1, 2, or 3, or (5) --CH.sub.2 --O--CH.sub.2 --Y-- wherein Y is a valence bond or --(CH.sub.2).sub.k -- wherein k is 1 or 2; wherein Q.sub.3 is ##STR229## wherein R.sub.3 is hydrogen or alkyl of 1 to 4 carbon atoms, inclusive; wherein R.sub.23 is ##STR230## wherein R.sub.25 is ##STR231## wherein C.sub.g H.sub.2.sbsb.g is alkylene of 1 to 9 carbon atoms, inclusive, with 1 to 5 carbon atoms, inclusive, in the chain between --CR.sub.5 R.sub.6 -- and terminal methyl, wherein R.sub.5 and R.sub.6 are hydrogen, alkyl of 1 to 4 carbon atoms, inclusive, or fluoro, being the same or different, with the proviso that one of R.sub.5 and R.sub.6 is fluoro only when the other is hydrogen or fluoro; ##STR232## wherein R.sub.5 and R.sub.6 are as defined above with the proviso that neither R.sub.5 nor R.sub.6 is fluoro when Z is oxa (--O--); wherein Z represents an oxa atom (--O--) or C.sub.j H.sub.2.sbsb.j wherein C.sub.j H.sub.2.sbsb.j is a valence bond or alkylene of 1 to 9 carbon atoms, inclusive, with 1 to 6 carbon atoms, inclusive between --CR.sub.5 R.sub.6 -- and the phenyl ring; wherein T is alkyl of 1 to 4 carbon atoms, inclusive, fluoro, chloro, trifluoromethyl, or --OR.sub.7 -- wherein R.sub.7 is alkyl of 1 to 4 carbon atoms, inclusive, and s is 0, 1, 2, or 3, with the proviso that not more than two T's are other than alkyl and when s is 2 or 3 the T's are either the same or different; or ##STR233## wherein R.sub.30 is (1) --COOR.sub.19

(2) --(ch.sub.2 n(r.sub.18).sub.2 ##STR234## wherein R.sub.19 is (a) alkyl of 1 to 12 carbon atoms, inclusive,

(b) cycloalkyl of 3 to 10 carbon atoms, inclusive,

(c) aralkyl of 7 to 12 carbon atoms, inclusive,

(d) phenyl,

(e) phenyl substituted with 1, 2, or 3 chloro or alkyl of 1 to 4 carbon atoms, inclusive, ##STR235## wherein R.sub.34 is phenyl, p-bromophenyl, p-biphenylyl, p-nitrophenyl, p-benzamidophenyl, or 2-napththyl, and wherein R.sub.35 is hydrogen or benzoyl,

(m) hydrogen, or

(n) a pharmacologically acceptable cation; and wherein R.sub.18 hydrogen, alkyl of 1 to 12 carbon atoms, inclusive, benzyl, or phenyl, being the same or different;

wherein X'is cis--CH.dbd.CH--, --C.tbd.C--, or --CH.sub.2 CH.sub.2 --; and wherein .about. indicates attachment in alpha or beta configuration; including the lower alkanoates thereof.

58. A compound according to claim 57 wherein X' is cis--CH.dbd.CH--.

59. A compound according to claim 57 wherein X' is --C.tbd.C--.

60. A compound according to claim 59 wherein Q.sub.3 is ##STR236## wherein R.sub.3 is as defined in claim 61.

61. A compound according to claim 60 wherein R.sub.23 is ##STR237##

62. A compound according to claim 61 wherein L is trimethylene, and where, if R.sub.30 is --CH.sub.2 N(R.sub.18).sub.2 or ##STR238## one R.sub.18 is hydrogen, methyl, or phenyl, and the other R.sub.18 is hydrogen, or, if R.sub.30 is --COOR.sub.19, R.sub.19 is (a) hydrogen, (b) methyl, (c) ethyl, ##STR239## (j) p-phenylphenacyl, or (k) a pharmacologically acceptable cation.

63. A compound according to claim 62 wherein R.sub.25 is n-pentyl.

64. 9-Deoxy-6.delta.,9.alpha.-epoxy-13,14-didehydro-PGF.sub.1, methyl ester, less polar and more polar isomers, compounds according to claim 63.

65. (6S)-13,14-Didehydro-PGI.sub.1, methyl ester, a compound according to claim 64.

66. (6R)-13,14-Didehydro-PGI.sub.1, methyl ester, a compound according to claim 64.

67. 9-Deoxy-6.delta.,9.alpha.-epoxy-13,14-didehydro-PGF.sub.1, less polar and more polar isomers, compounds according to claim 63.

68. (6S)-13,14-Didehydro-PGI.sub.1, a compound according to claim 67.

69. (6R)-13,14-Didehydro-PGI.sub.1, a compound according to claim 67.

70. A compound according to claim 59 wherein Q.sub.3 is ##STR240## wherein R.sub.3 is as defined in claim 57.

71. A compound according to claim 70 wherein R.sub.23 is ##STR241##

72. A compound according to claim 71 wherein L is trimethylene, and where, if R.sub.30 is --CH.sub.2 N(R.sub.18).sub.2 or ##STR242## one R.sub.18 is hydrogen, methyl, or phenyl, and the other R.sub.18 is hydrogen, or if R.sub.30 is --COOR.sub.19, R.sub.19 is (a) hydrogen, (b) methyl, (c) ethyl, ##STR243## (j) p-phenylphenacyl, or (k) a pharmacologically acceptable cation.

73. A compound according to claim 72 wherein R.sub.25 is n-pentyl.

74. 9-Deoxy-6.delta.,9.alpha.-epoxy-13,14-didehydro-(15R)-PGF.sub.1, methyl ester, less polar and more polar isomers, compounds according to claim 73.

75. (6S,15R)-13,14-Didehydro-PGF.sub.1, methyl ester, a compound according to claim 74.

76. (6R,15R)-13,14-Didehydro-PGF.sub.1, methyl ester, a compound according to claim 74.

77. 9-Deoxy-6.xi.,9.alpha.-epoxy-13,14-didehydro-(15R)-PGF.sub.1, less polar and more polar isomers, compounds according to claim 73.

78. (6S,15R)-13,14-Didehydro-PGF.sub.1, a compound according to claim 77.

79. (6R,15R)-13,14-Didehydro-PGF.sub.1, a compound according to claim 77.

80. A compound according to claim 57 wherein X' is --CH.sub.2 CH.sub.2 --.

81. A compound according to claim 80 wherein Q.sub.3 is ##STR244## wherein R.sub.3 is defined as in claim 57.

82. A compound according to claim 81 wherein R.sub.23 is ##STR245##

83. A compound according to claim 82 wherein L is --(CH.sub.2).sub.d -- wherein d is 1 to 5, inclusive.

84. A compound according to claim 83 wherein L is trimethylene and where, if R.sub.30 is --CH.sub.2 N(R.sub.18).sub.2 or ##STR246## one R.sub.18 is hydrogen, methyl, or phenyl, and the other R.sub.18 is hydrogen, or if R.sub.30 is --COOR.sub.19, R.sub.19 is (a) hydrogen, (b) methyl, (c) ethyl, ##STR247## (j) p-phenylphenacyl, or (k) a pharmacologically acceptable cation.

85. A compound according to claim 84 wherein R.sub.25 is n-pentyl.

86. 9-Deoxy-6.xi.,9.alpha.-epoxy-13,14-dihydro-PGF.sub.1, methyl ester, less polar and more polar isomers, compounds according to claim 85.

87. (6S)-13,14-Dihydro-PGI.sub.1, methyl ester, a compound according to claim 86.

88. (6R)-13,14-Dihydro-PGI.sub.1, methyl ester, a compound according to claim 86.

89. 9-Deoxy-6.xi.,9.alpha.-epoxy-13,14-dihydro-PGF.sub.1, less polar and more polar isomers, compounds according to claim 85.

90. (6S)-13,14-Dihydro-PGI.sub.1, a compound according to claim 89.

91. (6R)-13,14-Dihydro-PGI.sub.1, a compound according to claim 89.

92. A compound according to claim 84 wherein R.sub.25 is ##STR248##

93. A compound according to claim 84 wherein R.sub.25 is ##STR249##

94. A compound according to claim 82 wherein L is --(CH.sub.2).sub.t --CF.sub.2 wherein t is 2, 3, or 4.

95. A compound according to claim 94 wherein t is 2, and where, if R.sub.30 is --CH.sub.2 N(R.sub.18).sub.2 or ##STR250## one R.sub.18 is hydrogen, methyl, or phenyl, and the other R.sub.18 is hydrogen, or if R.sub.30 is --COOR.sub.19, R.sub.19 is (a) hydrogen, (b) methyl, (c) ethyl, ##STR251## (j) p-phenylphenacyl, or (k) a pharmacologically acceptable cation.

96. A compound according to claim 95 wherein R.sub.25 is n-pentyl.

97. 2,2-Difluoro-9-deoxy-6.xi.,9.alpha.-epoxy-13,14-dihydro-PGF.sub.1, methyl ester, less polar and more polar compounds according to claim 96.

98. 2,2-Difluoro-9-deoxy-6.xi.,9.alpha.-epoxy-13,14-dihydro-PGF.sub.1, sodium salt, less polar and more polar compounds according to claim 96.

99. 2,2-Difluoro-9-deoxy-6.xi.,9.alpha.-epoxy-13,14-dihydro-PGF.sub.1, amide, less polar and more polar compounds according to claim 96.

100. A compound according to claim 95 wherein R.sub.25 is ##STR252##

101. 2,2-Difluoro-9-deoxy-6.xi.,9.alpha.-epoxy-13,14-dihydro-16-phenoxy-17, 1 8,19,20-tetranor-PGF.sub.1, methyl ester, less polar and more polar compounds according to claim 100.

102. 2,2-Difluoro-9-deoxy-6.xi.,9. alpha.-deoxy-13,14-dihydro-16-phenoxy-17,18,19,20-tetranor-PGF.sub.1, sodium salt, less polar and more polar compounds according to claim 100.

103. 2,2-Difluoro-9-deoxy-6.xi.,9.alpha.-epoxy-13,14-dihydro-16-phenoxy-17, 18,19,20-tetranor-PGF.sub.1, amide, less polar and more polar compounds according to claim 100.

104. A compound according to claim 95 wherein R.sub.25 is ##STR253##

105. 2,2-Difluoro-9-deoxy-6.xi., 9.alpha.-epoxy-13,14-dihydro-17-phenyl-18,19,20-trinor-PGF.sub.1, methyl ester, less polar and more polar compounds according to claim 104.

106. 2,2-Difluoro-9-deoxy-6.xi.,9.alpha.-epoxy-13,14-dihydro-17-phe nyl-18,19,20-trinor-PGF.sub.1, sodium salt, less polar and more polar compounds according to claim 104.

107. 2,2-Difluoro-9-deoxy-6.xi.,9. alpha.-epoxy-13,14-dihydro-17-phenyl-18,19,20-trinor-PGF.sub.1, amide, less polar and more polar compounds according claim 104.

108. A compound according to claim 82 wherein L is --CH.sub.2 -CH.dbd.CH--A-- wherein A is a valence bond or --(CH.sub.2).sub.h -- wherein h is 1, 2, or 3.

109. A compound according to claim 108 wherein A is a valence bond and where, if R.sub.30 is --CH.sub.2 N(R.sub.18).sub.2 or ##STR254## one R.sub.18 is hydrogen, methyl, or phenyl, and the other R.sub.18 is hydrogen, or if R.sub.30 is --COOR.sub.19, R.sub.19 is (a) hydrogen, (b) methyl, (c) ethyl, ##STR255## (j) p-phenylphenacyl, or (k) a pharmacologically acceptable salt.

110. A compound according to claim 109 wherein R.sub.25 is n-pentyl.

111. A compound according to claim 109 wherein R.sub.25 is ##STR256##

112. A compound according to claim 109 wherein R.sub.25 is ##STR257##

113. A compound according to claim 80 wherein Q.sub.3 is ##STR258##

114. 9-Deoxy-6.xi.,9.alpha.-epoxy-13,14-dihydro-15-deoxy-PGF.sub.1, methyl ester, less polar and more polar compounds according to claim 113.

115. (6S)-13,14-Dihydro-15-deoxy-PGI.sub.1, methyl ester, a compound according to claim 114.

116. (6R)-13,14-Dihydro-15-deoxy-PGI.sub.1, methyl ester, a compound according to claim 114.