1. Chemical and physical properties of vitamin D
Domina Petric, MD

2. Essential features of the chemical structure are:
Side-chain-substituted, open-ring steroid
Cis-Triene structure
Open positions on carbon atoms at positions 1 (ring) and 25 (side chain)
November 20, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

3. Chemical structures of the vitamin D group are:
Vitamin D2: ergocalciferol
Vitamin D3: cholecalciferol
25-OH-Vitamin D3
1,25-(OH)2-Vitamin D3
November 20, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

4. Vitamin D nomenclature
Vitamin D is the generic descriptor for all steroids exhibiting qualitatively the biological activity of cholecalciferol.
These compounds contain the intact A, C and D steroid rings, being ultimately derived in vivo by photolysis of the B ring of 7-dehydrocholesterol.
That process frees the A ring from the rigid structure of the C and D rings, yielding conformational mobility in which the A ring undergoes rapid interconversion between two chair configurations.
November 20, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

5. Ergocalciferol
Vitamin D-active compounds also have either of two types of isoprenoid side chains attached to the steroid nucleus at C-17 of the D ring.
One side chain contains nine carbons and a single double bond.
Vitamin D-active compounds with that structure are derivatives of ergocalciferol (vitamin D2).
November 20, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

6. Medicineonline.com
November 20, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

7. Ergocalciferol
This vitamer can be produced synthetically by the photolysis of plant sterols.
November 20, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

8. Cholecalciferol
The other type of side chain consists of eight carbons and contains no double bonds.
Vitamin D-active compounds with that structure are derivatives of cholecalciferol (vitamin D3).
Vitamin D3 is produced metabolically through a natural process of photolysis of dehydrocholesterol on the surface of skin exposed to ultraviolet irradiation (sunlight).
November 20, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

9.
November 20, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

10. Active forms
The metabolically active forms of vitamin D are ring- (at C-1) and side chain-hydroxylated derivatives of vitamins D2 and D3.
November 20, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

11. Vitamin D chemistry
Vitamin D-active compounds tend to exist in extended conformations due to the 180° rotation of the A ring about the 6,7 single bond.
The hydroxyl group on C-3 is thus in the β position (above the plane of the A ring) in the closed forms and in the α position (below the plane of the A ring) in the stretched forms.
November 20, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

12. Vitamin D chemistry
Rotation about the 5,6 double bond can also occur by the action of light or iodine to interconvert the biologically active 5,6-cis compounds to 5,6-trans compounds, which show little or no vitamin D activity.
November 20, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

13. Physical properties
Vitamins D2 and D3 are white to yellowish powders that are:
insoluble in water
moderately soluble in fats, oils and ethanol
freely soluble in acetone, ether and petroleum ether
November 20, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

14. Solubility of D2 and D3 WATER FATS, OILS, ETHANOL Freely soluble in
Insoluble in
WATER
insoluble
Moderately soluble in
FATS, OILS, ETHANOL
soluble
Freely soluble in
soluble
ACETONE, ETHER, PETROLEUM ETHER
November 20, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

15. Physical properties
Both vitamin D2 and D3 show strong ultraviolet (UV) absorption, with a maximum at 264 nm.
Vitamin D is sensitive to oxygen, light and iodine.
Heating or mild acidity can convert it to the 5,6-trans and other inactive forms.
November 20, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

16. Physical properties
In solution, both vitamins D2 and D3 undergo reversible, temperature-dependent isomerization to pre-vitamin D, forming an equilibrium mixture with the parent vitamin.
November 20, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

17. Vitamin D biopotency
Those vitamers that require metabolic activation (cholecalciferol and ergocalciferol) are less biopotent than those that are more proximal to the points of metabolic functioning (25-OH-vitamin D).
November 20, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

18. Vitamin D biopotency Compound Relative biopotency
Vitamin D2 (ergocalciferol)
100
Vitamin D3 (cholecalciferol)
Dihydrotachysterol
5-10
25-OH-cholecalciferol
1,25-(OH)2-cholecalciferol
1α-OH-cholecalciferol
November 20, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc

19. Literature
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc
November 20, 2018
Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc