3. stereochemistry of steroids
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Transcript of 3. stereochemistry of steroids
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Stereo chemistryPrepared by
Dr. N.GOPINATHANASSISTANT PROFESSOR
DEPARTMENT OF PHARMACEUTICAL CHEMISTRYFACULTY OF PHARMACY
SRI RAMACHANDRA UNIVERSITYCHENNAI-116TAMILNADU
INDIA
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The stereo chemistry of the rings markedly affects biological activity of a given class of steroidsThere are six asymmetric carbon atoms 5,8,9,10,13,14 in the nucleus.Therefore 64 optically active forms are possible
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• It can exist in two conformations namely chair form and boat form.
• Chair conformation is more stable than boat conformation due to less angle strain.
• Hence all cyclohexane rings • exist in chair form
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• Hydrogen or functional groups on the β side of the molecule are denoted by solid lines and the α side is denoted by dotted lines.
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A/B trans
• The hydrogen atom at C-5 has α configuration, which is opposite from the c-19 angular methyl group β, making the A/B ring juncture trans
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Rings B/C and C/D - trans• The configuration of 8 β and 9 α hydrogens
and 14 α hydrogen and C-18 angular methyl group denotes trans fusion for rings B/C and C/D.
• Cis and trans relationship of the four rings may be expressed in terms of the back bone.
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5 α cholestane have trans- anti –trans –anti-trans back boneAnti denotes orientation of ring that are connected to each other and have trans type relationship
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5 β cholestane has Cis –Syn- trans-anti-trans back bone in which the A/B rings are fused Cis.The term Syn is used in a similar fashion as anti to define a Cis type relationship.
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• The number of possible optical isomer is 256. n= 8
• If the chiral centre in the side chain C-20 is also included the number of possible optical isomer will be 512. n= 9
• Two types• Deal with fused rings• Configuration of substituent at C3 & C17
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In the fully saturated nucleus, there are six chiral centres and hence there will be 64 n=6 optically active forms. [ theoratically possible]
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It is of worth mentioning that only few exist actually while many cannot exist due to steric limitation.Oxidative degradation method gives a great deal of evidence for the stereo chemistry of the nucleus.In A/B fusion both cis and trans were found in the natural steroids.
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X-ray analysis reveal that the fusion of the rings B and C was trans.Steroid is a flat which can be explained only if the fusion ring B and C has occurred together in trans manner.Only trans B/C fusion takes place in natural steroid.Ring C/D posses trans fusion.
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Mostly steroids have trans C/D fusion exception in cardiac glycoside and toad poison in which the fusion is cis.Hydrogen at C-9 is trans to methyl group at C-10.
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• The methyl groups at C-10 & C-13 are Cis
• NMR spectroscopy is quite useful in steroid chemistry.
• Angular methyl groups undergo coupling with certain protons on the steroid nucleus.
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It is also found that peak width of angular methyl group half height for trans fused isomer is larger than that for cis fused isomer
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Configuration of hydroxyl group at C-3
• β series found in all natural steroids.• The prefix β indicates that it lies above
the plane of molecule.• If hydroxyl group lies below the plane it
gives rise to α series.
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Thank you