Chemistry of Vitamin D
Chemistry of Vitamin D
The structures of vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) and their provitamins are presented in Figure 1 on the right. Vitamin D is a generic term and indicates a molecule of the general structure shown for rings A, B, C, and D with differing side chain structures. The A, B, C, and D ring structure is derived from the cyclopentanoperhydrophenanthrene ring structure for steroids. Technically vitamin D is classified as a seco-steroid. Seco-steroids are those in which one of the rings has been broken; in vitamin D, the 9,10 carbon-carbon bond of ring B is broken, and it is indicated by the inclusion of "9,10-seco" in the official nomenclature.
Vitamin D (calciferol) is named according to the revised rules of the
International Union of Pure and Applied Chemists (IUPAC). Because vitamin D is
derived from a steroid, the structure retains its numbering from the parent
compound cholesterol. Asymmetric centers are designated by using the R,S
notation; the configuration of the double bonds are notated E for "entgegen" or
trans, and Z for "zuzammen" or cis. Thus the official name of
vitamin D3 is
9,10-seco(5Z,7E)-5,7,10(19)cholestatriene-3b-ol,
and the official name of vitamin D2 is
9,10-seco(5Z,7E)-5,7,10(19), 22-ergostatetraene-3b-ol.
Vitamin D3 can be produced photochemically by the action of sunlight
or ultraviolet light from the precursor sterol 7-dehydrocholesterol which is
present in the epidermis or skin of most higher animals. The chief structural
prerequisite of a provitamin D is that it be a sterol with a
D5,7 diene double bond system in ring
B (Figure 2 to the left). The conjugated double
bond system in this specific location of the molecule allows the absorption of
light quanta at certain wavelengths in the UV range; this can readily be
provided in most geographical locations by natural sunlight (or UV-B). This
initiates a complex series of transformations (
partially summarized above in Fig. 1) that ultimately results in the appearance
of vitamin D3. Thus, it is important to appreciate that vitamin
D3 can be endogenously produced and that as long as the animal
(or human) has access on a regular basis to sunlight there is no dietary
requirement for this vitamin.
References:
Zhu, G.-D and Okamura, W.H. Synthesis of vitamin D (calciferol). Chem. Rev. 95:1877-1952 (1995).
Ikekawa, N. and Ishizuka, S. Molecular structure and biological activity of
vitamin D metabolites and their analogs. In: Molecular Structure and
Biological Activity of Steroids. Boca Raton: CRC Press, pp. 293-316
(1993).
Calverley, M.J. and Jones, G. Vitamin D. In: Antitumor Steroids, edited by Blickenstaff, R.T. San Diego: Academic Press, pp. 193-270 (1992).
Crowfoot-Hodgkin, D., Webster, M.S. and Dunitz, J.D. Structure of Calciferol. Chem. Industry 1148-1149 (1957).
Figure 1. Structural relationship of vitamin D3
(cholecalciferol) and vitamin D2 (ergocalciferol) with their
respective provitamins, cholesterol, and a classic steroid hormone, cortisol
(see inset box). The two structural representations presented at the bottom
for both vitamin D3 and vitamin D2 are equivalent; these
are simply different ways of drawing the same molecule. It is to be emphasized
that vitamin D3 is the naturally occurring form of the vitamin; it
is produced from 7-dehydrocholesterol, which is present in the skin, by the
action of sunlight (see Figure 2). Vitamin D2 (which is
equivalently potent to vitamin D3 in humans and many mammals, but
not birds) is produced commercially by the irradiation of the plant sterol
ergosterol with ultraviolet light.
Figure 2: Photochemical pathway of production of vitamin D3
(cholecalciferol) from 7-dehydrocholesterol. The starting point is the
irradiation of a provitamin D, which contains the mandatory
D5,7-conjugated double bonds; in the
skin this is 7-dehydrocholesterol. After absorption of a quantum of light from
sunlight (UV-B), the activated molecule can return to the ground state and
generate at least six distinct products. The four steroids that do not have a
broken 9, 10-carbon bond (provitamin D, lumisterol, pyrocalciferol, and
isopyrocalciferol) represent the four diastereomers with either an
a- or b-orientation
of the methyl group on carbon-10 and the hydrogen on carbon-9. The two
secosteroid products, vitamin D3, previtamin D3, and
tachysterol3 have differing positions of the three conjugated double
bonds. In the skin, the principal product is previtamin D3, which
then undergoes a 1,7-sigmatropic hydrogen transfer from C-19 to C-9, yielding
the final vitamin D3: Vitamin D3 can be drawn as either
a 6-s-trans representation or as 6-s-cis
representation depending upon the state of rotation about the 6,7-single bond.
The resulting vitamin D3, which is formed in the skin, is removed by
binding to the plasma transport protein, the vitamin D-binding protein (DBP),
present in the capillary bed of the dermis. The DBP-D3 then enters
the general circulatory system.
The structures of vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) and their provitamins are presented in Figure 1 on the right. Vitamin D is a generic term and indicates a molecule of the general structure shown for rings A, B, C, and D with differing side chain structures. The A, B, C, and D ring structure is derived from the cyclopentanoperhydrophenanthrene ring structure for steroids. Technically vitamin D is classified as a seco-steroid. Seco-steroids are those in which one of the rings has been broken; in vitamin D, the 9,10 carbon-carbon bond of ring B is broken, and it is indicated by the inclusion of "9,10-seco" in the official nomenclature. 