CIS 3,4-dihydroxy-2-(3-methylbutanoyl)-5-(3-methylbutyl)-4-(4-methylpentanoyl)cyclopent-2-en-1-derivatives, substantially enantiomerically pure compositions and methods

1. A potassium salt of (+)-(4S,5R)-3,4-dihydroxy-2-(3-methylbutanoyl)-5-(3-methylbutyl)-4-(4-methylpentanoyl)cyclopent-2-en-1-one having the structure:

2. A crystal of the potassium salt of claim 1 , wherein the crystal has a monoclinic space group P 21 21 2, and unit cell dimensions of a=23.3110(9) Å, α=90°, b=28.9052(12) Å, β=90°, c=13.6845(5) Å, and γ=90°.

3. The crystal of claim 2 , wherein the crystal has the three-dimensional atomic coordinates set forth in the following table:

x

y

z

U(eq)

C(1)

 7524(2)

5106(1)

 9242(3)

 28(1)

C(2)

 8024(2)

4959(1)

 9927(3)

 35(1)

C(3)

 7914(2)

4506(1)

10298(3)

 33(1)

C(4)

 7453(2)

4302(1)

 9756(3)

 34(1)

C(5)

 7216(2)

4643(1)

 8998(3)

 33(1)

C(6)

 7115(2)

5428(1)

 9834(3)

 36(1)

C(7)

 6892(4)

5255(2)

10809(5)

 72(2)

C(8)

 6566(3)

5590(2)

11380(4)

 50(1)

C(9)

 6337(3)

5389(3)

12359(5)

 68(2)

C(10)

 5872(6)

5053(5)

12195(8)

148(6)

C(11)

 6796(4)

5225(3)

13006(6)

 91(3)

C(12)

 8204(2)

4288(1)

11112(3)

 41(1)

C(13)

 8714(3)

4528(2)

11556(5)

 56(2)

C(14)

 8911(3)

4318(2)

12552(5)

 60(2)

C(15)

 8487(5)

4435(3)

13312(5)

 93(3)

C(16)

 9491(5)

4512(4)

 12823(11)

159(6)

C(17)

 7316(2)

4476(2)

 7954(3)

 39(1)

C(18)

 6870(2)

4671(2)

 7236(4)

 44(1)

C(19)

 6917(3)

4494(2)

 6194(4)

 54(1)

C(20)

 6405(3)

4629(3)

 5597(5)

 74(2)

C(21)

 7461(4)

4659(3)

 5703(5)

 82(2)

O(1)

 7752(1)

5356(1)

 8454(2)

 34(1)

O(2)

 8426(2)

5226(1)

10086(3)

 42(1)

O(3)

 7256(2)

3907(1)

 9822(3)

 43(1)

O(4)

 7004(1)

5799(1)

 9500(2)

 38(1)

O(5)

 8047(2)

3916(1)

11452(3)

 60(1)

C(22)

 7596(2)

6286(1)

 5706(3)

 32(1)

C(23)

 7561(2)

6826(2)

 5706(4)

 39(1)

C(24)

 7773(2)

6981(2)

 6619(3)

 35(1)

C(25)

 8071(2)

6608(2)

 7085(3)

 30(1)

C(26)

 8089(2)

6191(2)

 6411(3)

 33(1)

C(27)

 7030(2)

6134(1)

 6157(3)

 35(1)

C(28)

 6532(2)

6085(2)

 5470(4)

 44(1)

C(29)

 5957(2)

6096(2)

 5957(4)

 50(1)

C(30)

 5435(2)

6099(2)

 5260(4)

 54(1)

C(31)

 4893(3)

6202(3)

 5806(6)

 75(2)

C(32)

 5377(3)

5650(3)

 4727(5)

 69(2)

C(33)

 8688(2)

6152(2)

 5906(4)

 43(1)

C(34)

 8850(3)

5656(2)

 5614(4)

 53(1)

C(35)

 8940(3)

5313(2)

 6443(5)

 60(2)

C(36)

 9068(4)

4832(2)

 5990(6)

 77(2)

C(37)

 9412(4)

5462(3)

 7133(5)

 84(2)

C(38)

 7655(2)

7431(2)

 7050(3)

 39(1)

C(39)

 7350(4)

7795(2)

 6449(5)

 70(2)

C(40)

 7632(4)

8042(3)

 5651(7)

 87(2)

C(41)

 7251(5)

8330(3)

 5056(7)

108(3)

C(42)

 8045(6)

8295(5)

  6214(12)

172(6)

O(6)

 7666(2)

6098(1)

 4775(2)

 41(1)

O(7)

 7349(2)

7029(1)

 5011(3)

 52(1)

O(8)

 8285(1)

6599(1)

 7913(2)

 34(1)

O(9)

 6986(1)

6066(1)

 7050(2)

 38(1)

O(10)

 7759(2)

7512(1)

 7914(3)

 45(1)

C(43)

 9206(2)

2357(2)

11169(3)

 32(1)

C(44)

 9254(2)

2831(2)

10658(4)

 36(1)

C(45)

 9825(2)

2899(2)

10303(3)

 34(1)

C(46)

10172(2)

2515(1)

10586(3)

 32(1)

C(47)

 9823(2)

2157(1)

11149(3)

 32(1)

C(48)

 8995(2)

2406(2)

12207(3)

 37(1)

C(49)

 9293(3)

2753(2)

12844(4)

 50(1)

C(50)

 9393(4)

2593(2)

13886(5)

 74(2)

C(51)

 9820(5)

2928(3)

14482(7)

106(3)

C(52)

 9616(8)

3368(3)

14555(6)

167(7)

C(53)

 9965(6)

2714(4)

15395(7)

115(3)

C(54)

10026(2)

3288(2)

 9736(3)

 33(1)

C(55)

 9587(2)

3651(2)

 9436(4)

 45(1)

C(56)

 9221(3)

3489(2)

 8539(5)

 59(2)

C(57)

 8725(3)

3809(3)

 8372(6)

 82(2)

C(58)

 9567(4)

3424(4)

 7645(6)

108(3)

C(59)

 9882(2)

1677(2)

10713(3)

 36(1)

C(60)

 9653(2)

1295(2)

11353(4)

 42(1)

C(61)

 9602(3)

 834(2)

10846(5)

 67(2)

C(62)

 9336(4)

 470(2)

11526(6)

 81(2)

C(63)

10172(5)

 682(2)

10454(8)

125(5)

O(11)

 8798(1)

2080(1)

10663(2)

 37(1)

O(12)

 8825(1)

3073(1)

10574(3)

 53(1)

O(13)

10687(1)

2447(1)

10439(3)

 44(1)

O(14)

 8606(2)

2161(1)

12507(2)

 45(1)

O(15)

10531(1)

3326(1)

 9471(2)

 35(1)

C(64)

 6773(2)

7178(2)

12470(4)

 47(1)

C(65)

 7186(2)

6744(2)

12389(3)

 40(1)

C(66)

 7458(2)

6767(1)

11475(3)

 31(1)

C(67)

 7333(2)

7202(2)

11015(3)

 34(1)

C(68)

 7027(2)

7519(2)

11725(4)

 44(1)

C(69)

 6192(3)

6998(2)

12142(4)

 54(1)

C(70)

 5847(3)

6754(3)

12876(6)

 72(2)

C(71)

 5325(4)

6482(3)

12490(7)

 95(3)

C(72)

 4752(4)

6633(4)

12595(7)

100(3)

C(73)

 4721(6)

7091(4)

12195(9)

135(4)

C(74)

 4301(5)

6345(7)

 12259(12)

174(7)

C(75)

 7464(3)

7874(2)

12165(4)

 49(1)

C(76)

 8000(3)

7660(2)

12596(4)

 50(1)

C(77)

 8409(3)

7997(2)

13104(5)

 54(1)

C(78)

 8696(3)

8341(2)

12393(5)

 66(2)

C(79)

 8864(3)

7718(3)

13668(7)

 89(3)

C(80)

 7868(2)

6439(1)

11068(3)

 27(1)

C(81)

 8128(2)

6080(1)

11742(3)

 34(1)

C(82)

 8581(2)

6290(2)

12429(3)

 36(1)

C(83)

 9073(2)

6516(2)

11867(4)

 50(1)

C(84)

 8812(2)

5905(2)

13095(4)

 49(1)

O(16)

 6741(2)

7354(1)

13432(3)

 56(1)

O(17)

 7214(2)

6461(1)

13049(2)

 46(1)

O(18)

 7471(1)

7341(1)

10200(2)

 35(1)

O(19)

 6045(2)

7027(1)

11291(3)

 55(1)

O(20)

 8024(1)

6460(1)

10215(2)

 31(1)

O(21)

 6520(2)

3179(1)

10191(3)

 50(1)

O(22)

 9560(4)

5349(3)

 10090(10)

 96(4)

K(1)

 8740(1)

5960(1)

 9107(1)

 32(1)

K(2)

 7682(1)

3139(1)

10764(1)

 32(1)

K(3)

 7153(1)

6676(1)

 8756(1)

 28(1)

K(4)

 6484(1)

2234(1)

10709(1)

  33(1).

4. A pharmaceutical composition comprising the potassium salt of claim 1 and a pharmaceutically acceptable carrier.

5. A method of treating a condition responsive to PPARγ modulation in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising (+)-(4S,5R)-3,4-dihydroxy-2-(3-methylbutanoyl)-5-(3-methylbutyl)-4-(4-methylpentanoyl)cyclopent-2-en-1-one having the structure:

or a salt or crystal thereof and a pharmaceutically acceptable carrier.

6. A method of treating a condition responsive to GPR120 modulation in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising (+)-(4S,5R)-3,4-dihydroxy-2-(3-methylbutanoyl)-5-(3-methylbutyl)-4-(4-methylpentanoyl)cyclopent-2-en-1-one having the structure:

or a salt or crystal thereof and a pharmaceutically acceptable carrier.

7. A method of treating a metabolic disturbance in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising (+)-(4S,5R)-3,4-dihydroxy-2-(3-methylbutanoyl-5-(3-methylbutyl)-4-(4-methylpentanoyl)cyclopent-2-en-1-one having the structure:

or a salt or crystal thereof and a pharmaceutically acceptable carrier.

8. Crystalline (+)-(4S,5R)-3,4-dihydroxy-2-(3-methylbutanoyl)-5-(3-methylbutyl)-4-(4-methylpentanoyl)cyclopent-2-en-1-one potassium salt (1:1).

9. Crystalline (−)-(4R,5S)-3,4-dihydroxy-2-(3-methylbutanoyl)-5-(3-methylbutyl)-4-(4-methylpentanoyl)cyclopent-2-en-1-one potassium salt (1:1).

10. A method of treating a condition responsive to PPARγ modulation in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a substantially enantiomerically pure composition of (+)-(4S,5R)-3,4-dihydroxy-2-(3-methylbutanoyl)-5-(3-methylbutyl)-4-(4-methylpentanoyl)cyclopent-2-en-1-one having the structure:

or a salt or crystal thereof.

11. A method of treating a condition responsive to GPR120 modulation in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a substantially enantiomerically pure composition of (+)-(4S,5R)-3,4-dihydroxy-2-(3-methylbutanoyl)-5-(3-methylbutyl)-4-(4-methylpentanoyl)cyclopent-2-en-1-one having the structure:

or a salt or crystal thereof.

12. A method of treating a metabolic disturbance in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a substantially enantiomerically pure composition of (+)-(4S,5R)-3,4-dihydroxy-2-(3-methylbutanoyl)-5-(3-methylbutyl)-4-(4-methylpentanoyl)cyclopent-2-en-1-one having the structure:

or a salt or crystal thereof.

13. The method of claim 5 , 6 , 7 , 10 , 11 , or 12 , wherein the salt thereof is a potassium salt having the structure:

14. The method of claim 10 , 11 , or 12 , wherein the composition further comprises a pharmaceutically acceptable carrier.

15. The method of claim 5 or 10 , wherein the condition is selected from the group consisting of diabetes and obesity.

16. The method of claim 7 or 12 , wherein the metabolic disturbance is diabetes.

17. The method of claim 7 or 12 , wherein administration of the pharmaceutical composition results in a decrease in glucose and/or lipid levels.