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How do you know if a group on a steroid is alpha or beta?
- Alpha = dotted line = opposite side as angular methyls
- Beta = Solid line = same side as angular methyls
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What groups determine the top (Beta) face of the steroid?
The C13 and C10 methyls (must be straight lines)
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If the C5-H is alpha, the A/B ring fusion is in what conformation?
 - Trans (coplanar)
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What is this nucleus called, and how many carbons does it have?
Estrane = 18 carbons
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What is this nucleus called, and how many carbons does it have?
Androstane = 19 carbons
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What is this nucleus called, and how many carbons does it have?
Pregnane = 21 carbons
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The position of the double bond is critical, how is it designated in the name of the steroid?
- If the double bond joins consecutively numbered carbon atoms:
- Specify only the lower numbered carbon involved
- If the double bond joins consecutively numbered carbon atoms:
- Both carbons must be indicated
- higher numbered carbon is contained in parentheses
Also can use Greek capital letter Delta with superscripted position numbers
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How do you name a steroid?
- 1. Identify the sterid nucleus
- 2. Identify specific functional groups.
- 3. Designate the alpha/beta stereochemistry of each group
- 4. Indicate double bonds in the name (i.e pregnene or pregnadiene)
- 5. Indicate the position of the double bond.
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Name the bond and nucleus of this structure:
- 4-Pregnene
- OR
- Delta4-Pregnene
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Name the bond and nucleus of this structure:
- 5(10)-Estrene
- OR
- Delta 5(10)-Estrene
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Name the bond and nucleus of this structure:
- 1,3,5(10)-Estriene
- OR
- 1,3,5(10)-Estriene
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What does the endine –ene mean (i.e. pregnene)?
One double bond
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What does the endine –diene mean (i.e. pregnadiene)?
Two double bonds
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What does the endine –triene mean (i.e. pregnatriene)?
Three double bonds
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All corticosteroids are derivatives of what?
- Pregnane
- (contain the C21 carbon sterid nucleus)
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Structural modifications of the steroid hormones have been made resulting in modification of their pharmacokinetic and pharmacodynamic properties. These modifications have been done to:
- 1. Increase or modify biological activity
- 2. Increase oral activity and duration of action
- 3. Effect a separation of biological action
- 4. Obtain better solubility properties
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Natural corticoids are all derivatives of:
- Delta 4-21-hydroxypregnen-3,20-dione
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Which face of the corticoid structure is mist critical for binding to the glucocorticoid receptor?
Beta face
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Which face of the corticoid structure is mist critical for binding to the mineralcorticoid receptor?
Alpha face
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What type of bonding will be most critical at the glucocorticoid receptor?
Hydrogen bonding
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Is the Pregnane nucleus essential for corticosteroid activity?
- Yes
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Do derivatives of estrange or androstene have corticosteroid activity?
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Is this group essential for corticosteroid action, what is it called?
- Yes
- 17 Beta –glycolyl or Ketol group
- (Must be free)
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Is this structure essential for mineralcorticoid or glucocorticoid activity?
Both
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This group is essential, what SAR changes can be made to this group without deactivating the compounds corticoid activity?
- C21-OH replacement with F
- Cl can also be used, but only active topically at glucocorticoid receptors
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Is this group essential for corticoid activity, what is its name?
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What would happen if you reduced the =O on this ring?
Inactivation
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What would happen if you reduced the double bond on this structure?
Inactivation
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What is the activity of 3 alpha-hydroxysteroid dehydrogenase?
- Reduces the steroid 3- keto group to a 3 alpha-OH
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What is the activity of 5 Beta reductase?
- Reduces the 4-5 double bond to a 5 Beta-H
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What steroid characteristics are required for this metabolic inactivating reaction to take place?
Free C21-OH (cannot be an ester)
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What is this functional group called?
Dihydroxyacetone
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What reaction does this 17 alpha-OH facilitate?
- D ring oxidation
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Why do most Glucocorticoids have a 17 alpha-OH group?
- Enhances Glucocorticoid receptor affinity and potency
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Generally speaking, adding Oxygen containing function groups to a corticoid will have what effect on Glucocorticoid and Mineralcorticoid activity?
- Increase Glucocorticoid activity by enhancing H bonding
- Decrease Mineralcorticoid activity
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Adding an 11B-OH to this molecule (at the point indicated) will affect the activity in what way?
- Best functional group for enhancing Glucocorticoid action
- H-donor at GC receptor
- Critical for potent GC acitivty
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Adding an 11-keto to this molecule (at the point indicated) will affect the activity in what way?
- H accepting, but retains activity
- Rapidly and reversibly reduced to 11B-OH in vivo by 11B-hydroxysteroid dehydrogenase
- 11B-OH is ideal for potent GC activity
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What characteristics does a 17 alpha OH impart to this molecule?
- Enhanced GC activity
- Synergistic activity with 11B-OH
- Decreased DOA due to increased C17 oxidation
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A molecule with both an 11B-OH and 17a-OH will have what activity profile?
- Better activity at GC receptors than either functional group alone (synergistic activity)
- Greater C17 oxidation due to the 17a-OH
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If you treat this molecule with acid, how will it affect this group?
No effect, protected by angular methyls (at C13 and C10)
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If you treat this molecule with acid, how will it affect this group?
- Sluggishly esterify
- Slow reaction due to protection by the D ring and 17B ketol group
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If you treat this molecule with acid, how will it affect this group?
Readily esterify as it is the least hindered OH group
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