Terpenes: The Isoprene Rule

1. Terpenes: The Isoprene Rule

2. CH3 H2C CH CH2 C Terpenes • Terpenes are natural products that are structurally related to isoprene. or Isoprene(2-methyl-1,3-butadiene)

3. CH3 CH2 CH2 CHCH2CH2CCH CH3C Terpenes • Myrcene (isolated from oil of bayberry) is a typical terpene. or

4. The Isoprene Unit • An isoprene unit is the carbon skeleton of isoprene (ignoring the double bonds) Myrcene contains two isoprene units.

5. The Isoprene Unit • The isoprene units of myrcene are joined "head-to-tail." head tail tail head

6. Common Carbon Backbone

9. Terpenes Classification of Terpenes • Class Number of carbon atoms • Monoterpene 10 • Sesquiterpene 15 • Diterpene 20 • Sesterpene 25 • Triterpene 30 • Tetraterpene 40

10. OH O H Terpenes Representative Monoterpenes a-Phellandrene(eucalyptus) Menthol(peppermint) Citral(lemon grass)

11. OH O H Terpenes Representative Monoterpenes a-Phellandrene(eucalyptus) Menthol(peppermint) Citral(lemon grass)

12. Terpenes Representative Monoterpenes a-Phellandrene(eucalyptus) Menthol(peppermint) Citral(lemon grass)

13. Terpenes Representative Sesquiterpenes H a-Selinene(celery)

14. Terpenes Representative Sesquiterpenes H a-Selinene(celery)

15. Terpenes Representative Sesquiterpenes a-Selinene(celery)

16. OH Terpenes Representative Diterpenes Vitamin A

17. OH Terpenes Representative Diterpenes Vitamin A

18. Terpenes Representative Diterpenes Vitamin A

19. Common Terpenes

20. Limonene

21. Limonene

22. Rearrangement

23. Terpenes

24. Terpenes

25. Isoprene / Biosynthesis

30. Terpene Biosynthesis Formation of geranyl pyrophosphate

32. Farnesyl Pyrophosphate

33. Formation of Squalene, the Precursor of Cholesterol

34. Terpenes Representative Triterpene tail-to-tail linkage of isoprene units Squalene(shark liver oil)

35. Isoprene LinksHeads or Tails?

36. Squalene, a triterpene, is a precursor of steroids

37. Steroids • Many hormones are steroids

38. The B, C, and D rings are trans fused Methyl groups at C-10 and C-13 are called angular methyl groups

39. The A and B rings are also trans fused in most naturally occurring steroids Substituents on the same side of the steroid ring system as the angular methyl groups are b-substituents Thoseon the opposite side of the plane of the ring system are a-substituents

42. Biosynthesis of Cholesterol

43. Synthetic Steroids

45. TERPENE BIOSYNTHESESin detailIsopentenyl Pyrophosphate:The Biological Isoprene Unit

46. The Biological Isoprene Unit • The isoprene units in terpenes do not come from isoprene. • They come from isopentenyl pyrophosphate. • Isopentenyl pyrophosphate (5 carbons) comes from acetate (2 carbons) via mevalonate (6 carbons).

47. O CH3 O CH3COH HOCCH2CCH2CH2OH OH CH3 O O H2C CCH2CH2OPOPOH The Biological Isoprene Unit 3 Mevalonic acid Isopentenyl pyrophosphate

48. CH3 O O H2C CCH2CH2OPOPOH OPP Isopentenyl Pyrophosphate or Isopentenyl pyrophosphate

49. OPP OPP Isopentenyl and Dimethylallyl Pyrophosphate Isopentenyl pyrophosphate is interconvertible with2-methylallyl pyrophosphate. • Dimethylallyl pyrophosphate has a leaving group (pyrophosphate) at an allylic carbon; it is reactive toward nucleophilic substitution at this position. Isopentenyl pyrophosphate Dimethylallyl pyrophosphate

50. Carbon-Carbon Bond Formation in Terpene Biosynthesis