Introduction to Steroids MC

label with numbers ignore DB

Stereochemistry : cis and trans ring junctions

A. cis ring junction – both substituents at the ring junction (including H) are on the same face

B. trans ring junction – the substituents at the ring junction (including H) are on opposite faces

C. Assume all trans ring junctions, especially if you don’t see H atom stereochemistry

which is preferred cis or trans

trans

Skeleton Stem Name Modification – consider additional functional groups

Location and type of functional groups on a-face

 This face is typically involved in hydrophobic interactions.

 Hydrophilic substituents on this face will disturb these interactions.

 Bulky substituents on this face will disturb these interactions

Location and type of functional groups on B-face

 This face is typically involved in H-bonding interactions.

 Polar/hydrophilic substituents on this face will enhance these interactions

Location and type of functional group at position 3

 Alcohol (OH) or ketone (C=O) are typically present

Location and type(s) of functional group(s) on the D-ring

 Typically see 2 carbon side chain at C-17

Unsaturation at positions 1 (delta1) and 4 (delta4) changes the geometry of the A ring

 Increases glucocorticoid activity 3-4x

 Decreases mineralocorticoid activity significantly

Cholesterol Biosynthesis

Biochemical Roles for Cholesterol

Conversion to glucocorticoid adrenal hormones (cortisol, hydrocortisone)

Biological Targets for Steroid Hormones

A. Corticosteroid or Adrenocorticoid receptors

• Mineralocorticoid receptors

• Glucocorticoid receptors

Nucleus

The receptor dimer can then interact with various regions of cellular DNA (hormone responsive elements), as well as with transcriptional factors