columbia大學(xué)有機(jī)化學(xué)課件26_11_16 html

1、26.11Steroids:CholesterolFundamental framework of steroids is the tetracyclic unit shown.Structure of CholesterolCH3HCholesterol has the fundamental steroid skeleton modified as shown.CH3CH3CH3HCH3HHOStructure of CholesterolCH3HSome parts of the cholesterol molecule areisoprenoid.But other parts don

2、t obey theisoprene rule.Also, cholesterol has 27 carbons,which is not a multiple of 5.CH3CH3CH3HCH3HHOStructure of CholesterolCholesterol is biosynthesized from the triterpenesqualene.In the first step, squalene isconverted to its 2,3-epoxide.Biosynthesis of CholesterolCholesterol is biosynthesized

3、from the triterpenesqualene.In the first step, squalene isconverted to its 2,3-epoxide.O2, NADH, enzymeOBiosynthesis of CholesterolTo understand the second step, we need to look at squalene oxide in a different conformation, one that is in a geometry suitable for cyclization.OBiosynthesis of Cholest

4、erolTo understand the second step, we need to look at squalene oxide in a different conformation, one that is in a geometry suitable for cyclization.OOBiosynthesis of CholesterolCyclization is triggered by epoxide ring opening.H+OBiosynthesis of CholesterolHOCyclization is triggered by epoxide ring

5、opening.H+O+Biosynthesis of CholesterolHOHLoss of a proton is accompanied by a series of hydride shifts and methyl migrations.HOHH OH2 H+HBiosynthesis of CholesterolThe product of this rearrangement is atriterpene called lanosterol.A number ofenzyme-catalyzed steps follow that convert lanosterol to

6、cholesterol.HOHHBiosynthesis of CholesterolCholesterol is the biosynthetic precursor to a large number of important steroids:Bile acids Vitamin D Corticosteroids Sex hormonesCholesterol26.12Vitamin DCH3HCholesterol is the precursor to vitamin D.Enzymes dehydrogenate cholesterol to introduce a second

7、double bond in conjugation with the existing one.Theproduct of this reaction is called 7-dehydrocholesterol.CH3CH3CH3HCH3HHOCholesterolCH3CH3HSunlight converts 7-dehydrocholesterol on the skins surface to vitamin D3.CH3CH3CH3HHO7-DehydrocholesterolCH3CH3HInsufficient sunlight can lead to a deficienc

8、y of vitamin D3, interfering with Ca2+ transport and bone development. Rickets can result.CH3CH3HOVitamin D326.13Bile AcidsCH3HOxidation in the liver degrades the cholesterol side chain and introduces OH groups at various positions on thesteroid skeleton. bile acids.Cholic acid is the most abundant

9、of theCH3CH3CH3HCH3HHOCholesterolOOHHOHSalts of cholic acid amides (bile salts), such as sodium taurocholate, act as emulsifying agents to aid digestion.HO CH3CH3CH3HHHOHCholic AcidONHCH2CH2SO3NaHOHHO CH3CH3CH3HHHOHSodium Taurocholate26.14CorticosteroidsCH3HEnzymatic degradation of the side chain an

10、d oxidation of various positions on the steroid skeleton convert cholesterol to corticosteroids.CH3CH3CH3HCH3HHOCholesterolOHOCortisol is the most abundant of the corticosteroids. Enzyme-catalyzed oxidation of cortisol gives cortisone.OCH3HOCHHOH3HHCortisolOHOCorticosteroids are involved in maintain

11、ing electrolyte levels, in the metabolism of carbohydrates, and in mediating the allergic response.OCH3OCHHOH3HHCortisone26.15Sex HormonesOTestosterone is the main male sex hormone.H3COHH3CHHHTestosteroneHOEstradiol is a female sex hormone involved in regulating the menstrual cycle and in reproduction.H3COHHHHEstradiolOSupresses ovulation during pregnancy.OH3CH3CHHHProgesterone26.16CarotenoidsCarotenoids are naturally occurring pigments.Structurally, carotenoids are te