Vitamin side chain analogs

As possible modulators of vitamin D metabolism, several nitrogen-containing side chain analogs have been nthesized from the 22-aldehyde. The 2S-aza vitamin [scheme (1 l)] has been found to be an inhibitor of D activity, while the 24-aza [scheme (12)] and the 24-amino vitamin [scheme (13)] derivatives (J. Chu,... 

FIGURE 8.18 Dolichol phosphate is an initiation point for the synthesis of carbohydrate polymers in animals. The analogous alcohol in bacterial systems, undecaprenol, also known as bactoprenol, consists of 11 isoprene units. Undecaprenyl phosphate delivers sugars from the cytoplasm for the synthesis of cell wall components such as peptidoglycans, lipopolysaccharides, and glycoproteins. Polyprenyl compounds also serve as the side chains of vitamin K, the ubiquinones, plastoquinones, and tocopherols (such as vitamin E). 

Yet an important application is the analogous isomerization of 1,4-diacetoxy-2-butene (13) to the 1,3-isomer 14 (cis/trans mixture) with a Pt CU catalyst - a key step of the BASF vitamin A synthesis (eq. (15)). The lower-boiling product is enriched to a yield of 95 % and is further hydroformylated to form the vitamin A side chain [25] (see Chapter 1). 

Our data demonstrate that specific side-chain modifications can yield novel vitamin D derivatives with unique properties. ZK 191784 is a first representative of a novel class of immunosuppressive vitamin D analogs with a considerable therapeutic window. Vitamin D compounds with a dissociated profile may represent... 

Mahonen A, Jaaskelainen T, Maenpaa PH. A novel vitamin D analog with two double bonds in its side chain A potent inducer of osteoblastic cell differentiation. Biochem Pharmacol. 1996 51 887-892. 

Guo, Y.D., S. Strugnell, D.W. Back, and G. Jones (1993). Transfected human liver cytochrome P-450 hydroxylates vitamin D analogs al different side-chain positions. Proc. Natl. Acad. Sci. USA 90, 8668-8672. 

Ethyl-6-methyl- and 2,6-dimethyl-3-pyridinol react with piperidine, di-methylamine, and morpholine in aqueous formaldehyde to form 4-dialkylamino-methylated products that have been used to prepare vitamin Be analogs XII-681 and XU-682. Reaction at the side-chain is not observed. 

In the vitamin K series the maximum effect was found in the vitamin K2 analog with 25 C-atoms in the side chain (Table II). The activity of this vitamin Kj form was even somewhat hi er than that of vitamin Ki (Wiss et al., 1959). This may serve as a hint that in addition to vitamin Kscm), Ktoo), Kjcto) (Section II, 3 and 4) this form may also occur in nature. 

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