3. stereochemistry of steroids

Stereo chemistryPrepared by

Dr. N.GOPINATHANASSISTANT PROFESSOR

DEPARTMENT OF PHARMACEUTICAL CHEMISTRYFACULTY OF PHARMACY

SRI RAMACHANDRA UNIVERSITYCHENNAI-116TAMILNADU

INDIA

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

• 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

• 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.

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

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.

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

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.

• 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

In the fully saturated nucleus, there are six chiral centres and hence there will be 64 n=6 optically active forms. [ theoratically possible]

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.

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.

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.

• 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.

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

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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