Pharmaceutical Chemistry II Vitamins D, K Joseph O. Oweta | PHC 3201

Vitamin D Vitamin D acts as a hormone, helping regulate the uptake of calcium from the intestines by promoting the synthesis of calcium-binding protein in the mucosal cells. Deficiency of this vitamin causes “rickets,” a condition of low levels of calcium, which results in soft and pliable bones, leading to bending and distortion.

Vitamin D (From Ergosterol ) The various forms of vitamin D are broken-open steroids referred to as secosteroids. The term vitamin D is currently applied to all steroids possessing biological activity like that of cholecalciferol. Irradiation of yeast ergosterol yields a 1:1 mixture of ergocalciferol and lumisterol() known as vitamin D1. The term vitamin D1 is largely obsolete b’se it's known that any Vitamin D activity is from Ergocalciferol Lumisterol is the (9β,10α) stereoisomer of ergosterol, and a product of its irradiation.

Vitamin D (From Ergosterol) Lumisterol is 19β,10α sterioisomer

Vitamin D

Vitamin D (From Ergosterol) Cholecalciferol (calciol, previously vitamin D3) is the form produced in vivo from the action of sunlight on 7-dehydrocholesterol in the skin. D3 therefore may not be regarded as a “vitamin” because its produced in the skin from sunlight (290 – 300nm) Only in absence of sunlight will D3 become a vitamin. Its regarded as a provitamin for the same reason

Photoconversion of 7-DHC TO d3

Bioactivation of Cholecaliferol

Ultraviolet Bath, Russia (Nat Brief exposure to UV C radiation provides the children with vitamin D

Vitamin K Introduction Named Vitamin K (fromthe German word Koagulation). Discovered as an antihaemorrhagic factor from studies on lipid free diets. Originally named Vitamin K1, IUPAC recommended the Term Phylloquinone, officially abbreviated as “K”. K2 was desingnated for Farnoquinone. Sveral other cpds were discovered but only varying in the number of attached isoprenoid units. The term Menaquinones (MK) was recommended by IUPAC

Vitamin K Introduction The menaquinones differin the number of prenyl units attached and specific compounds are designated menaquinone-n (MK-n) wheren represents the number of prenyl side chains. vitamin K2 is now known as MK-6. Vitamin K shall be discussed to mean phylloquinones and other menaquinones. The Generic Name for Phylloquinone is phytodione and is a preferec name among clincal practitioners

Vitamin K Introduction Naturally occurring vitamin K is found in two forms, depandant on the source: o Plants : Phylloquinone o Bacteria: Menaquinones Dietary Sources include are Green Leafy Vegetables, Olive oil etc Major Baceterial sources are the intestinal Flora especially gram positives. o Overall Contribution is Unknown.

Vitamin K chemistry all vitamin Ks are 2-methyl 1,4- naphthoquinonederivatives containing variable aliphatic sidechains at C3.

Vitamin K chemistry Menaquinones (Fig ) are a seriesof compounds that have a longer side chain with more unsaturation. This side chain may be composed of 1 to 13prenyl (isoprenyl) units.

Vitamin K chemistry Of particular historical note are the water- solublemenadione (2-methyl-1,4-naphthoquinone; vitamin K3),which is no longer marketed because of toxicities, and menadiol(2-methylnaphthalene-1,4- diol; vitamin K4). Menadione contains the naphthoquinone ring without any attached prenyls and can be thought of as MK-0

Futher Reading Chemistry and therapeutic application of the water soluble vitamins : Vitamin B Vitamin C