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

or a crystal thereof.

2. The substantially enantiomerically pure composition of claim 1 , wherein the crystal thereof 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 substantially enantiomerically pure composition of claim 2 , wherein the crystal thereof has the three-dimensional atomic coordinates (×10 4 ) and equivalent isotropic displacement parameters (Å 2 ×10 3 ) 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. The substantially enantiomerically pure composition of 1 , further comprising a pharmaceutically acceptable carrier.

5. A method of treating diabetes in a subject in need thereof comprising administering 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.

6. The method of claim 5 , wherein the salt thereof is selected from the group consisting of potassium, aluminum, calcium, copper, guanidinium, iron, lithium, magnesium, sodium, zinc, cinchonidine, cinchonine, and diethanolamine salts.

7. The method of claim 5 , wherein the substantially enantiomerically pure composition further comprises a pharmaceutically acceptable carrier.

8. The substantially enantiomerically pure composition according to claim 1 , wherein the enantiomerical purity of (+)-(4S,5R)-3,4-dihydroxy-2-(3-methylbutanoyl)-5-(3-methylbutyl)-4-(4-methylpentanoyl)cyclopent-2-en-1-one potassium salt or a crystal thereof is 98% or higher.

9. The substantially enantiomerically pure composition according to claim 1 , wherein the enantiomerical purity of (+)-(4S,5R)-3,4-dihydroxy-2-(3-methylbutanoyl)-5-(3-methylbutyl)-4-(4-methylpentanoyl)cyclopent-2-en-1-one potassium salt or a crystal thereof is 99% or higher.

10. The substantially enantiomerically pure composition according to claim 1 , wherein the enantiomerical purity of (+)-(4S,5R)-3,4-dihydroxy-2-(3-methylbutanoyl)-5-(3-methylbutyl)-4-(4-methylpentanoyl)cyclopent-2-en-1-one potassium salt or a crystal thereof is 99.5% or higher.

11. The method according to claim 5 , wherein the enantiomerical purity of (+)-(4S,5R)-3,4-dihydroxy-2-(3-methylbutanoyl)-5-(3-methylbutyl)-4-(4-methylpentanoyl)cyclopent-2-en-1-one or a salt or crystal thereof is 98% or higher.

12. The method according to claim 5 , wherein the enantiomerical purity of (+)-(4S,5R)-3,4-dihydroxy-2-(3-methylbutanoyl)-5-(3-methylbutyl)-4-(4-methylpentanoyl)cyclopent-2-en-1-one or a salt or crystal thereof is 99% or higher.

13. The method according to claim 5 , wherein the enantiomerical purity of (+)-(4S,5R)-3,4-dihydroxy-2-(3-methylbutanoyl)-5-(3-methylbutyl)-4-(4-methylpentanoyl)cyclopent-2-en-1-one or a salt or crystal thereof is 99.5% or higher.